Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.

Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS.

High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.

COVID-19 Recovery: Consistent Absence of Cerebrospinal Fluid Biomarker Abnormalities in Patients With Neurocognitive Post-COVID Complications.

BACKGROUND: To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC). METHODS: Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination, lumbar puncture, and venipuncture ≥3 months after COVID-19 symptom onset. Healthy volunteers were included. CSF and plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike antigen (N-Ag, S-Ag), and CSF biomarkers of immune activation and neuronal injury were analyzed. RESULTS: SARS-CoV-2 N-Ag or S-Ag were undetectable in all samples and no participant had pleocytosis. We detected no significant differences in CSF and plasma cytokine concentrations, albumin ratio, IgG index, neopterin, ß2M, or in CSF biomarkers of neuronal injury and astrocytic damage. Furthermore, principal component analysis (PCA1) analysis did not indicate any significant differences between the study groups in the marker sets cytokines, neuronal markers, or anti-cytokine autoantibodies. CONCLUSIONS: We found no evidence of ongoing viral replication, immune activation, or CNS injury in plasma or CSF in patients with neurocognitive PCC compared with COVID-19 controls or healthy volunteers, suggesting that neurocognitive PCC is a consequence of events suffered during acute COVID-19 rather than persistent viral CNS infection or residual CNS inflammation.

The relationship between serum astroglial and neuronal markers and AQP4 and MOG autoantibodies.

BACKGROUND: Certain demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) exhibit serum autoantibodies against aquaporin-4 (αAQP4) and myelin oligodendrocyte glycoprotein (αMOG). The variability of the autoantibody presentation warrants further research into subtyping each case. METHODS: To elucidate the relationship between astroglial and neuronal protein concentrations in the peripheral circulation with occurrence of these autoantibodies, 86 serum samples were analyzed using immunoassays. The protein concentration of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL) and tau protein was measured in 3 groups of subcategories of suspected NMOSD: αAQP4 positive (n = 20), αMOG positive (n = 32) and αMOG/αAQP4 seronegative (n = 34). Kruskal-Wallis analysis, univariate predictor analysis, and multivariate logistic regression with ROC curves were performed. RESULTS: GFAP and NFL concentrations were significantly elevated in the αAQP4 positive group (p = 0.003; p = 0.042, respectively), and tau was elevated in the αMOG/αAQP4 seronegative group (p < 0.001). A logistic regression model to classify serostatus was able to separate αAQP4 seropositivity using GFAP + tau, and αMOG seropositivity using tau. The areas under the ROC curves (AUCs) were 0.77 and 0.72, respectively. Finally, a combined seropositivity versus negative status logistic regression model was generated, with AUC = 0.80. CONCLUSION: The 3 markers can univariately and multivariately classify with moderate accuracy the samples with seropositivity and seronegativity for αAQP4 and αMOG.

Glial fibrillary acidic protein, neurofilament light, matrix metalloprotease 3 and fatty acid binding protein 4 as non-invasive brain tumor biomarkers.

BACKGROUND: Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival. METHODS: Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays. RESULTS: High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas. CONCLUSIONS: GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.

Retrospective cohort evaluation of non-HIV Castleman disease from a single academic center in Beijing, China.

The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).

CO2-Mediated Alkali-Neutralization Curdlan Hydrogels for Potential Wound Healing Application.

Physical hydrogels of natural polysaccharides are considered as ideal candidates for wound dressing due to their natural biological activity and no harmful cross-linking agents. However, it remains a challenge to fabricate such hydrogel dressings in a facile and low-cost way. Herein, we reported an easy and cost-effective method to construct CO2-mediated alkali-neutralization Curdlan (CR) hydrogels without using an external cross-linking agent. Two types of hydrogels (denoted as CR-NaOH and CR-Na3PO4, respectively) were fabricated by dissolving CR powders in a NaOH or Na3PO4 aqueous solution, followed by keeping the CR alkaline solutions in air. The obtained pure CR hydrogels possessed a tunable porous structure with walls containing different forms of nanofibrils. These hydrogels exhibited much higher gel strength by comparison with the gels prepared by conventional heating treatment. They were flexible, stretchable, twistable, and conformable to arbitrarily curved skins. Moreover, they exhibited ideal swellability, proper degradability, and water vapor transmission rate, and their physicochemical properties were closely related to CR concentration in the alkaline solution. These two hydrogels also supported the growth of L929 cells. Importantly, studies on wound healing revealed that both 3CR-NaOH and 3CR-Na3PO4 hydrogels were capable of accelerating the wound healing process through recruiting more macrophages/fibroblasts, inducing more collagen deposition and neovascularization (α-SMA and CD31) without carrying any exogenous bioactive components. In conclusion, the present work not only reported promising materials for application in wound therapy but also offered a facile and safe manufacturing procedure for generating pure CR physical hydrogels with better performance.

SnO2/SnS heterojunction anchoring on CMK-3 mesoporous network improves the reversibility of conversion reaction for lithium/sodium ions storage.

Tin oxide-based (SnO2) materials show high theoretical capacity for lithium and sodium storage benefiting from a double-reaction mechanism of conversion and alloying reactions. However, due to the limitation of the reaction thermodynamics and kinetics, the conversion reaction process of SnO2usually shows irreversibility, resulting in serious capacity decay and hindering the further application of the SnO2anode. Herein, SnO2/SnS heterojunction was anchored on the surface and inside of CMK-3 byinsitusynthesis method, forming a stable 3D structural material (SnO2/SnS@CMK-3). The electrochemical properties of SnO2/SnS@CMK-3 composite show high capacity and reversible conversion reaction, which was attributed to the synergistic effect of CMK-3 and SnO2/SnS heterojunction. To further investigate the influence of the heterojunction on the reversibility of the conversion reaction, the Gibbs free energy (ΔG) was calculated using density functional theory. The results show that SnO2/SnS heterojunction has a closer to zero ΔGfor lithium/sodium ion batteries compared to SnO2, indicating that the heterojunction enhances the reversibility of the conversion reaction in chemical reaction thermodynamics. Our work provides insights into the reversibility of the conversion reaction of SnO2-based materials, which is essential for improving their electrochemical performance.

Fluorescent Probes Based on Ag NPs@N/GQDs and Molecularly Imprinted Polymer for Sensitive Detection of Noradrenaline in Bananas.

Fluorescence intensity and selective recognition ability are crucial factors in determining the analytical techniques for fluorescent probes. In this study, a core-shell fluorescent material, composed of silver nanoparticles@nitrogen-doped graphene quantum dots (Ag NPs@N/GQDs), was synthesised using mango leaves as the raw material through a thermal cracking method, resulting in strong fluorescence luminescence intensity. By employing noradrenaline as a template molecule and using a surface molecular imprinting technique, a molecularly imprinted membrane (MIP) was formed on the surface of the fluorescent material, that was subsequently eluted to obtain a highly specific, fluorescent probe capable of recognising noradrenaline. The probe captured various concentrations of noradrenaline using the MIP, which decreased the fluorescence intensity. Then a method for detecting trace amounts of noradrenaline was established. This method exhibited a linear range from 0.5 -700 pM with a detection limit of 0.154 pM. The proposed method was implemented in banana samples. Satisfactory recoveries were confirmed at four different concentrations. The method presented a relative standard deviation (RSD) of less than 5.0%.

Diagnostic strategy of metagenomic next-generation sequencing for gram negative bacteria in respiratory infections.

OBJECTIVE: This study aims to identify the most effective diagnostic method for distinguishing pathogenic and non-pathogenic Gram-negative bacteria (GNB) in suspected pneumonia cases using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples. METHODS: The effectiveness of mNGS was assessed on BALF samples collected from 583 patients, and the results were compared with those from microbiological culture and final clinical diagnosis. Three interpretational approaches were evaluated for diagnostic accuracy. RESULTS: mNGS outperformed culture significantly. Among the interpretational approaches, Clinical Interpretation (CI) demonstrated the best diagnostic performance with a sensitivity of 87.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 98.3%. CI's specificity was significantly higher than Simple Interpretation (SI) at 37.9%. Additionally, CI excluded some microorganisms identified as putative pathogens by SI, including Haemophilus parainfluenzae, Haemophilus parahaemolyticus, and Klebsiella aerogenes. CONCLUSION: Proper interpretation of mNGS data is crucial for accurately diagnosing respiratory infections caused by GNB. CI is recommended for this purpose.

Clinical Features of Paediatric Inflammatory Epidermolysis Bullosa Acquisita: A Case Series Study.

Epidermolysis bullosa acquisita (EBA) rarely develops in childhood. This study retrospectively recruited paediatric patients with EBA (age ≤ 16 years), diagnosed by clinical and histopathological features and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA), and reviews their clinical manifestations, histopathology, immunological features, and responses to various treatments. All 7 included patients presented with inflammatory EBA. Among them, 3 had a bullous pemphigoid-like phenotype. Pathologically, in addition to dermal-epidermal blistering, in all patients, the distribution of neutrophils was superficial perivascular or interstitial, or in the dermal papilla. Mixed neutrophils and eosinophils were detected in 2 of the 3 patients with bullous pemphigoid-like phenotypes. In addition to treatment with glucocorticoids, dapsone was administered in 4 patients, while thalidomide and sulfasalazine were administered in 1 patient. All patients responded to the these therapies. Relapse was mainly due to reduction and cessation of glucocorticoids. In conclusion, EBA in childhood may be unique, and thus distinct from its adult counterpart. Specific treatment and follow-up protocols are required for therapy of this rare autoimmune skin disease in children.

High-Flow Nasal Oxygen versus Conventional Nasal Cannula in Preventing Hypoxemia in Elderly Patients Undergoing Gastroscopy with Sedation: A Randomized Controlled Trial.

Background: We aimed to compare the prevention of hypoxemia using High-flow nasal oxygen (HFNO) or regular nasal tubing (CNC) in elderly patients undergoing gastroscopy with sedation. Methods: This study was a prospective, randomized, controlled trial conducted at a single center. We included elective patients aged 65 and above who were undergoing gastroscopy with sedation. In the intervention group (HFNO), we set the oxygen flow rate to 60 liters per minute with an oxygen fraction (FiO2) of 0.6, while in the control group (CNC), it was 6 liters per minute. The primary outcome was the occurrence of hypoxemia (defined as Spo2 < 90%). Results: A total of 125 participants were enrolled (HFNO group: n = 63; CNC group: n = 62). The occurrence of hypoxemia was found to be significantly lower in the HFNO group compared to the CNC group (3.2% vs. 22.6%, p = 0.001). Additionally, a significantly shorter duration of low oxygen levels was observed in the HFNO group [0.0 seconds (0.0-13.0)] compared to the CNC group [0.0 seconds (0.0-124.0), p<0.001]. Moreover, a higher minimum Spo2 value was achieved in the HFNO group [99.0% (98.0-100.0) vs. 96.5% (91.0-99.0), p < 0.001], and a shorter recovery time was recorded [0.5 minutes (0.0-0.5) vs. 0.5 minutes (0.0-1.0), p = 0.016] in comparison to the CNC group. There were no differences in terms of comfort level [0 (0-4) vs. 0 (0-5), p = 0.268] between the two groups. Conclusions: The HFNO system was determined to be a safe and highly effective method for oxygen delivery, leading to a reduction in the occurrence of hypoxemia in elderly patients undergoing gastroscopy with sedation. It is recommended that HFNO be considered as the standard approach for management in this population.

α-Ketoglutarate alleviates osteoarthritis by inhibiting ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway.

Osteoarthritis (OA) is the most common degenerative joint disorder that causes disability in aged individuals, caused by functional and structural alterations of the knee joint. To investigate whether metabolic drivers might be harnessed to promote cartilage repair, a liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics approach was carried out to screen serum biomarkers in osteoarthritic rats. Based on the correlation analyses, α-ketoglutarate (α-KG) has been demonstrated to have antioxidant and anti-inflammatory properties in various diseases. These properties make α-KG a prime candidate for further investigation of OA. Experimental results indicate that α-KG significantly inhibited H2O2-induced cartilage cell matrix degradation and apoptosis, reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione (GSH)/glutathione disulfide (GSSG) levels, and upregulated the expression of ETV4, SLC7A11 and GPX4. Further mechanistic studies observed that α-KG, like Ferrostatin-1 (Fer-1), effectively alleviated Erastin-induced apoptosis and ECM degradation. α-KG and Fer-1 upregulated ETV4, SLC7A11, and GPX4 at the mRNA and protein levels, decreased ferrous ion (Fe2+) accumulation, and preserved mitochondrial membrane potential (MMP) in ATDC5 cells. In vivo, α-KG treatment inhibited ferroptosis in OA rats by activating the ETV4/SLC7A11/GPX4 pathway. Thus, these findings indicate that α-KG inhibits ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway, thereby alleviating OA. These observations suggest that α-KG exhibits potential therapeutic properties for the treatment and prevention of OA, thereby having potential clinical applications in the future.

The imaging findings of migraine with visual aura in a CADASIL patient.

Head MRI images of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients during migraine attacks are rare.

Polyhexamethylene guanidine accelerates the macrophage foamy formation mediated pulmonary fibrosis.

Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-ß1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.

A General Strategy Based on Hetero-Charge Coupling Effect for Constructing Single-Atom Sites.

Single-atom catalysts have emerged as cutting-edge hotspots in the field of material science owing to their excellent catalytic performance brought about by well-defined metal single-atom sites (M SASs). Herein, we report a novel synthesis strategy based on the hetero-charge coupling effect (HCCE) to prepare M SASs loaded on N and S co-doped porous carbon (M1/NSC). The proposed strategy was widely applied to prepare 17 types of M1/NSC composed of single or multi-metal with the integrated regulation of the coordination environment and electronic structure, exhibiting good universality and flexible adjustability. Furthermore, this strategy provided a low-cost method of efficiently synthesizing M1/NSC with high yields, that can produce more than 50 g catalyst at one time, which is key to large-scale production. Among various as-prepared unary M1/NSC catalysts, Fe1/NSC delivered excellent performance for electrocatalytic nitrate reduction to NH3 with high NH3 Faradaic efficiency of 86.6% and high NH3 yield rate of 1.50 mg h-1 mgcat.-1 at -0.6 V vs. RHE. Even using Fe1/NSC as a cathode in a Zn-nitrate battery, it exhibited a high open circuit voltage of 1.756 V and high energy density of 4.42 mW cm-2 with good cycling stability.

Lateral Offset Single-Mode Fiber-Based Fabry-Perot Interferometers with Vernier Effect for Hydrogen Sensing.

A high-sensitive optical fiber hydrogen (H2) sensor with Vernier effect by cascading three Fabry-Perot interferometers (FPIs) has been proposed. It is prepared by welding three sections of a single-mode fiber with a lateral offset structure and coating polydimethylsiloxane (PDMS) at the offset part to form three cascaded FPIs and generate a Vernier envelope spectrum. To realize H2 sensing, the hydrogen-sensitive material Pd/WO3 is fabricated and coated on the outside of the PDMS. Pd/WO3 will generate local heat when in contact with H2, which will cause the thermal expansion and refractive index change of PDMS and finally lead to the Vernier envelope wavelength shifting with the change of H2 concentration. Due to the Vernier effect, the H2 sensor can achieve a linear measurement sensitivity of 6.214 nm/% in the concentration range of 0-1%, which is 16.11 times that of a single FPI. The proposed H2 sensor possesses advantages of high sensitivity, easy preparation, compact structure, low cost, and easy long-distance transmission.

Haemonchus contortus HcL6 promoted the Th9 immune response in goat PBMCs by activating the STAT6/PU.1/NF-κB pathway.

Th9 cells play a crucial role in parasite immunity. The development of Th9 cells is facilitated by several cytokines. Key transcription factors, such as STAT6, STAT5, and PU.1, are known to enhance IL-9 expression during the Th9 immune response. NF-κB-mediated transduction pathways participate in the induction of IL-9. In a previous study, we unveiled a unique ribosomal protein derived from Haemonchus contortus excretory-secretory proteins (HcESPs) that interact with host Th9 cells. In the present study, the effects of the Haemonchus contortus ribosomal protein L6 domain DE-containing protein (HcL6) on IL-9 secretion, Th9 differentiation, and IL-9 transcription were assessed by employing ELISA, flow cytometry, and qPCR methodologies. The observations revealed the transcriptional upregulation of several key genes within the Th9 immune response pathway. Moreover, silencing STAT6, PU.1, and NF-κB was found to attenuate the Th9 immune response. In this study, we unveiled the Th9 immune response-inducing capabilities of HcL6 and elucidated some of its underlying mechanisms. These findings suggest that HcL6 is an immunostimulatory antigen capable of inducing the Th9 immune response. These insights could prove instrumental in identifying potential candidate antigens for the development of immunoprophylactic strategies against H. contortus infections.

Ni-catalyzed C-F activation to construct C-P bond with P-P(O) and P(O)OR mediation.

Here we developed an efficient Ni-catalyzed C-F bond phosphorylation of aryl fluorides via the crucial intermediates of P-P(O) and P(O)OR. P-P(O) mediated organophosphorus generation is observed for active aryl fluorides, whereas inactive aryl fluorides can also be activated and phosphorylated via a P(O)OR-mediated pathway, which is barely reported yet. Facile scale-up to the gram level and the upgrading of the bioactive molecule make this protocol to have promising applications in synthetic chemistry.