Inhibition of TGF-ß signaling in bone marrow endothelial cells promotes hematopoietic recovery in acute myeloid leukemia patients.

Although it is an effective treatment for acute myeloid leukemia (AML), chemotherapy leads to myelosuppression and poor hematopoietic reconstruction. Hematopoiesis is regulated by bone marrow (BM) endothelial cells (ECs), and BM ECs are dysfunctional in acute leukemia patients with poor hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation. Thus, it is crucial to explore the underlying mechanism of EC impairment and establish strategies for targeted therapy. TGF-ß signaling was found to be upregulated in ECs from AML patients in complete remission (CR ECs) and led to CR EC damage. Administration of a TGF-ß inhibitor rescued the dysfunction of ECs caused by TGF-ß1 expression in vitro, especially their hematopoiesis-supporting ability. Moreover, inhibition of TGF-ß expression repaired the BM EC damage triggered by chemotherapy in both AML patients in vitro and in an AML-CR murine model, and restored normal hematopoiesis without promoting AML progression. Mechanistically, our data reveal alterations in the transcriptomic pattern of damaged BM ECs, accompanied by the overexpression of downstream molecules TGF-ßR1, pSmad2/3, and functional genes related to adhesion, angiogenesis suppression and pro-apoptosis. Collectively, our findings reveal for the first time that the activation of TGF-ß signaling leads to BM EC dysfunction and poor hematopoietic reconstitution. Targeting TGF-ß represents a potential therapeutic strategy to promote multilineage hematopoiesis, thereby benefiting more cancer patients who suffer from myelosuppression after chemotherapy.

A novel hollow flower shaped Cu9S8 antibacterial agent for removing sulfonamide in water environment: effects of composite with magnetic biochar, differential adsorption, and mechanism study.

In this study, hollow nanoflower spherical Cu9S8 and Cu9S8/Fe3O4@BC with adsorption and antibacterial properties was prepared by coprecipitation and solvothermal method, respectively. The adsorption results showed that the Cu9S8 exhibited excellent adsorption performance on sulfonamide antibiotics (SAs), especially for sulfamethoxazole (SMZ). The optimal addition amount of Cu9S8 is 0.2 g, which results in a maximum adsorption capacity of 33.4 mg/g for SMZ within 120 min. The fitting results of adsorption and desorption kinetics and thermodynamics, as well as the conditions such as pH value and ionic strength were compared. It was found that different interactions led to the differential adsorption of SAs by Cu9S8. The desorption experiment further elucidated its adsorption mechanism. The large desorption capacity indicates that SAs on Cu9S8 can be further recovered and treated. The auto-deposition characteristics of Cu9S8 and the hysteresis loop of Cu9S8/Fe3O4@BC were studied to effectively recover Cu9S8 from aquatic environments. Additionally, more than 99% of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were exterminated by Cu9S8 and Cu9S8/Fe3O4@BC within 20 min. The above results suggested that the hollow nanoflower spherical Cu9S8 and Cu9S8/Fe3O4@BC composite materials can provide a new strategy for solving pollution problems and waste treatment.

River Surface Velocity Measurement for Rapid Levee Breach Emergency Response Based on DFP-P-LK Algorithm.

In recent years, the increasing frequency of climate change and extreme weather events has significantly elevated the risk of levee breaches, potentially triggering large-scale floods that threaten surrounding environments and public safety. Rapid and accurate measurement of river surface velocities is crucial for developing effective emergency response plans. Video image velocimetry has emerged as a powerful new approach due to its non-invasive nature, ease of operation, and low cost. This paper introduces the Dynamic Feature Point Pyramid Lucas-Kanade (DFP-P-LK) optical flow algorithm, which employs a feature point dynamic update fusion strategy. The algorithm ensures accurate feature point extraction and reliable tracking through feature point fusion detection and dynamic update mechanisms, enhancing the robustness of optical flow estimation. Based on the DFP-P-LK, we propose a river surface velocity measurement model for rapid levee breach emergency response. This model converts acquired optical flow motion to actual flow velocities using an optical flow-velocity conversion model, providing critical data support for levee breach emergency response. Experimental results show that the method achieves an average measurement error below 15% within the velocity range of 0.43 m/s to 2.06 m/s, demonstrating high practical value and reliability.

Recent Development of Biodegradable Occlusion Devices for Intra-Atrial Shunts.

Atrial septal defect (ASD) is the third most common type of structural congenital heart defect. Patent foramen ovale (PFO) is an anatomical anomaly in up to 25% of the general population. With the innovation of occlusion devices and improvement of transcatheter techniques, percutaneous closure has become a first-line therapeutic alternative for treatment of ASD and PFO. During the past few decades, the development of biodegradable occlusion devices has become a promising direction for transcatheter closure of ASD/PFO due to their biodegradability and improved biocompatibility. The purpose of this review is to comprehensively summarize biodegradable ASD/PFO occlusion devices, regarding device design, materials, biodegradability, and evaluation of animal or clinical experiments (if available). The current challenges and the research direction for the development of biodegradable occluders for congenital heart defects are also discussed.

Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation.

BACKGROUND: Radiation esophagitis (RE) is one of the most common clinical symptoms of regi-onal lymph node radiotherapy for breast cancer. However, there are fewer studies focusing on RE caused by hypofractionated radiotherapy (HFRT). AIM: To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes. METHODS: Between January and December 2022, we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F. RESULTS: Of the 64 patients in this study, 24 (37.5%) did not develop RE, 29 (45.3%) developed grade 1 RE (G1RE), 11 (17.2%) developed grade 2 RE (G2RE), and none developed grade 3 RE or higher. Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose, mean dose, relative volume 20-40, and absolute volume (AV) 20-40. Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE (P < 0.001). The optimal threshold for AV30 was 2.39 mL [area under the curve (AUC): 0.996; sensitivity: 90.9%; specificity: 91.1%]. The optimal threshold for AV35 was 0.71 mL (AUC: 0.932; sensitivity: 90.9%; specificity: 83.9%). CONCLUSION: AV30 and AV35 were significantly associated with G2RE. The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL, respectively.

SIRT6 positively regulates antiviral response in a bony fish, the Chinese perch Siniperca chuatsi.

SIRT6, a key member of the sirtuin family, plays a pivotal role in regulating a number of vital biological processes, including energy metabolism, oxidative stress, and immune system modulation. Nevertheless, the function of SIRT6 in bony fish, particularly in the context of antiviral immune response, remains largely unexplored. In this study, a sirt6 was cloned and characterized in a commercial fish, the Chinese perch (Siniperca chuatsi). The SIRT6 possesses conserved SIR2 domain with catalytic core region when compared with other vertebrates. Tissue distribution analysis indicated that sirt6 was expressed in all detected tissues, and the sirt6 was significantly induced following infection of infectious haemorrhagic syndrome virus (IHSV). The overexpression of SIRT6 resulted in significant upregulation of interferon-stimulated genes (ISGs), such as viperin, mx, isg15, irf3 and ifp35, and inhibited viral replication. It was further found that SIRT6 was located in nucleus and could enhance the expression of ISGs induced by type I and II IFNs. These findings may provide new information in relation with the function of SIRT6 in vertebrates, and with viral prevention strategy development in aquaculture.

Transcription of NOD1 and NOD2 and their interaction with CARD9 and RIPK2 in IFN signaling in a perciform fish, the Chinese perch, Siniperca chuatsi.

NOD1 and NOD2 as two representative members of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family play important roles in antimicrobial immunity. However, transcription mechanism of nod1 and nod2 and their signal circle are less understood in teleost fish. In this study, with the cloning of card9 and ripk2 in Chinese perch, the interaction between NOD1, NOD2, and CARD9 and RIPK2 were revealed through coimmunoprecipitation and immunofluorescence assays. The overexpression of NOD1, NOD2, RIPK2 and CARD9 induced significantly the promoter activity of NF-κB, IFNh and IFNc. Furthermore, it was found that nod1 and nod2 were induced by poly(I:C), type I IFNs, RLR and even NOD1/NOD2 themselves through the ISRE site of their proximal promoters. It is thus indicated that nod1 and nod2 can be classified also as ISGs due to the presence of ISRE in their proximal promoter, and their expression can be mechanistically controlled through PRR pathway as well as through IFN signaling in antiviral immune response.

Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment.

Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.

Trx4, a novel thioredoxin protein, is important for Toxoplasma gondii fitness.

BACKGROUND: To successfully replicate within the host cell, Toxoplasma gondii employs several mechanisms to overcome the host cell defenses and mitigate the harmful effects of the free radicals resulting from its own metabolic processes using effectors such as thioredoxin proteins. In this study, we characterize the location and functions of a newly identified thioredoxin in T. gondii, which was named Trx4. METHODS: We characterized the functional role of Trx4 in T. gondii Type I RH and Type II Pru strains by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The enzyme-catalyzed proximity labeling technique, the TurboID system, was employed to identify the proteins in proximity to Trx4. RESULTS: Trx4 was identified as a dense granule protein of T. gondii predominantly expressed in the parasitophorous vacuole (PV) and was partially co-localized with GRA1 and GRA5. Functional analysis showed that deletion of trx4 markedly influenced the parasite lytic cycle, resulting in impaired host cell invasion capacity in both RH and Pru strains. Mutation of Trx domains in Trx4 in RH strain revealed that two Trx domains were important for the parasite invasion. By utilizing the TurboID system to biotinylate proteins in proximity to Trx4, we identified a substantial number of proteins, some of which are novel, and others are previously characterized, predominantly distributed in the dense granules. In addition, we uncovered three novel proteins co-localized with Trx4. Intriguingly, deletion of trx4 did not affect the localization of these three proteins. Finally, a virulence assay demonstrated that knockout of trx4 resulted in a significant attenuation of virulence and a significant reduction in brain cyst loads in mice. CONCLUSIONS: Trx4 plays an important role in T. gondii invasion and virulence in Type I RH strain and Type II Pru strain. Combining the TurboID system with CRISPR-Cas9 technique revealed many PV-localized proximity proteins associated with Trx4. These findings suggest a versatile role of Trx4 in mediating the processes that occur in this distinctive intracellular membrane-bound vacuolar compartment.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Immunization with Live-Attenuated RHΔhad2a Strain Confers Partial Protective Immunity against Acute and Chronic Infection of Toxoplasma gondii in Mice.

Toxoplasmosis caused by Toxoplasma gondii is an important zoonosis of human and animal health significance. Current chemical therapeutics have side effects, and no commercially available vaccine is licensed for the prevention of toxoplasmosis in humans and most animals. Developing a safe and effective vaccine with long-term protection against T. gondii infection is necessary to control toxoplasmosis. HAD2a is a key member of the haloacid dehalogenase (HAD) phosphatase family, which is essential for T. gondii daughter budding. However, the role of HAD2a in T. gondii virulence remains unknown. In this study, we successfully constructed the had2a gene knockout strain in the T. gondii-type I RH strain (RHΔhad2a) and determined its role in virulence and vaccination. These results demonstrate that HAD2a played an important role in parasite daughter budding and in vitro replication. Knockout of the had2a gene attenuated the virulence of the T. gondii-type I RH strain. Vaccination with RHΔhad2a tachyzoites induced a Th1-biased immune response, provided partial protection against acute T. gondii infection in mice by highly virulent tachyzoites of RH and PYS (ToxoDB#9, Chinese I) strains, and conferred strong protection against challenge infection by cysts and oocysts of the less virulent type II Pru strain. These results demonstrate that T. gondii had2a is important for its in vitro proliferation and virulence in mice and that RHΔhad2a may be used as a candidate strain to generate a multiple gene knockout live-attenuated strain or be collaboratively applied with other live-attenuated strains to confer more effective protection against T. gondii infection.

Electrocardiographic characteristics of bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy.

OBJECTIVE: Patients treated with preoperative chemotherapy and immunotherapy for bladder cancer may be at increased risk of cardiotoxicity and electrophysiological abnormalities. This study aimed to analyze their electrocardiographic (ECG) alterations. METHODS: Patients with bladder cancer who were hospitalized and receiving tislelizumab plus nab-paclitaxel (TnP) were enrolled prospectively. ECG, cardiac biomarkers, and echocardiography were performed at baseline and the end of TnP. RESULTS: A total of 60 patients (76.7% males), including 30 muscle-invasive and 30 non-muscle-invasive bladder cancer, received three or four cycles of TnP, respectively. Hypertension was the commonest comorbidity (41.7%), and 25 patients (41.7%) were prescribed cardiovascular drugs. In comparison with baseline characteristics, cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were within normal ranges after TnP. However, echocardiographic parameter of left ventricular ejection fraction slightly decreased after TnP (62.81 ± 3.81% to 61.10 ± 4.37%, p = .011). The incidence of abnormal ECG increased from 65.0% at baseline to 76.7%, of which only a higher prevalence of fragmented QRS (fQRS) was observed (33.3% to 50.0%, p = .013; mainly in inferior leads). ECG parameters of QT dispersion (QTd) were prolonged significantly after the regimen (39.50 ± 11.37 to 44.20 ± 15.85 ms, p = .019). CONCLUSION: In bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy, the main ECG abnormality was fQRS and QTd, with relatively normal cardiac biomarkers and echocardiographic parameters. Regular ECG screening should be carried out carefully to detect potential cardiotoxicity in the long-term follow-up.

The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony.

Sexual development in Toxoplasma gondii is a multistep process that culminates in the production of oocysts, constituting approximately 50% of human infections. However, the molecular mechanisms governing sexual commitment in this parasite remain poorly understood. Here, we demonstrate that the transcription factors AP2XI-2 and AP2XII-1 act as negative regulators, suppressing merozoite-primed pre-sexual commitment during asexual development. Depletion of AP2XI-2 in type II Pru strain induces merogony and production of mature merozoites in an alkaline medium but not in a neutral medium. In contrast, AP2XII-1-depleted Pru strain undergoes several rounds of merogony and produces merozoites in a neutral medium, with more pronounced effects observed under alkaline conditions. Additionally, we identified two additional AP2XI-2-interacting proteins involved in repressing merozoite programming. These findings underscore the intricate regulation of pre-sexual commitment by a network of factors and suggest that AP2XI-2 or AP2XII-1-depleted Pru parasites can serve as a model for studying merogony in vitro.

Circ_0068481 Affects the Human Pulmonary Artery Smooth Muscle Cells' Progression by miR-361-3p/KLF5 Axis.

BACKGROUND: Uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). In this work, we defined the precise part of circ_0068481 in PASMC proliferation and migration induced by hypoxia. We hypothesized that circ_0068481 enhanced hypoxia-induced PASMC proliferation, invasion, and migration through the microRNA (miR)-361-3p/Krüppel-like factor 5 (KLF5) pathway. METHODS: Human PASMCs (hPASMCs) were exposed to hypoxic (3% O2) conditions. Circ_0068481, miR-361-3p, and KLF5 levels were gauged by qRT-PCR and western blot. Cell viability, proliferation, invasion, and migration were detected by XTT, EdU incorporation, transwell, and wound-healing assays, respectively. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were performed to confirm the direct relationship between miR-361-3p and circ_0068481 or KLF5. RESULTS: Circ_0068481 expression was increased in the serum of PAH patients and hypoxia-induced hPASMCs. Downregulation of circ_0068481 attenuated hypoxia-induced promotion in hPASMC proliferation, invasion, and migration. Circ_0068481 directly targeted miR-361-3p, and miR-361-3p downregulation reversed the inhibitory effects of circ_0068481 silencing on hypoxia-induced hPASMC proliferation, invasion, and migration. KLF5 was a direct miR-361-3p target, and miR-361-3p upregulation mitigated hypoxia-induced hPASMC proliferation, invasion, and migration by inhibiting KLF5 expression. Moreover, circ_0068481-induced KLF5 expression by binding to miR-361-3p in hypoxic hPASMCs. CONCLUSIONS: Circ_0068481 knockdown ameliorated hypoxia-induced hPASMC proliferation, invasion, and migration at least in part through the miR-361-3p/KLF5 axis.

A newly characterized dense granule protein (GRA76) is important for the growth and virulence of Toxoplasma gondii.

Pathogenicity of the zoonotic pathogen Toxoplasma gondii largely depends on the secretion of effector proteins into the extracellular milieu and host cell cytosol, including the dense granule proteins (GRAs). The protein-encoding gene TGME49_299780 was previously identified as a contributor to parasite fitness. However, its involvement in parasite growth, virulence and infectivity in vitro and in vivo remains unknown. Here, we comprehensively examined the role of this new protein, termed GRA76, in parasite pathogenicity. Subcellular localization revealed high expression of GRA76 in tachyzoites inside the parasitophorous vacuole (PV). However, its expression was significantly decreased in bradyzoites. A CRISPR-Cas9 approach was used to knock out the gra76 gene in the T. gondii type I RH strain and type II Pru strain. The in vitro plaque assays and intracellular replication showed the involvement of GRA76 in replication of RH and Pru strains. Deletion of the gra76 gene significantly decreased parasite virulence, and reduced the brain cyst burden in mice. Using RNA sequencing, we detected a significant increase in the expression of bradyzoite-associated genes such as BAG1 and LDH2 in the PruΔgra76 strain compared with the wild-type Pru strain. Using an in vitro bradyzoite differentiation assay, we showed that loss of GRA76 significantly increased the propensity for parasites to form bradyzoites. Immunization with PruΔgra76 conferred partial protection against acute and chronic infection in mice. These findings show the important role of GRA76 in the pathogenesis of T. gondii and highlight the potential of PruΔgra76 as a candidate for a live-attenuated vaccine.

Portal vein velocity predicts portal vein system thrombosis after splenectomy with esophagogastric devascularization.

BACKGROUND: Portal vein system thrombosis (PVST) is a potentially fatal complication after splenectomy with esophagogastric devascularization (SED) in cirrhotic patients with portal hypertension. However, the impact of portal vein velocity (PVV) on PVST after SED remains unclear. Therefore, this study aims to explore this issue. METHODS: Consecutive cirrhotic patients with portal hypertension who underwent SED at Tongji Hospital between January 2010 and June 2022 were enrolled. The patients were divided into two groups based on the presence or absence of PVST, which was assessed using ultrasound or computed tomography after the operation. PVV was measured by duplex Doppler ultrasound within one week before surgery. The independent risk factors for PVST were analyzed using univariate and multivariate logistic regression analysis. A nomogram based on these variables was developed and internally validated using 1000 bootstrap resamples. RESULTS: A total of 562 cirrhotic patients with portal hypertension who underwent SED were included, and PVST occurred in 185 patients (32.9%). Multivariate logistic regression analysis showed that PVV was the strongest independent risk factor for PVST. The incidence of PVST was significantly higher in patients with PVV ≤ 16.5 cm/s than in those with PVV > 16.5 cm/s (76.2% vs. 8.5%, p < 0.0001). The PVV-based nomogram was internally validated and showed good performance (optimism-corrected c-statistic = 0.907). Decision curve and clinical impact curve analyses indicated that the nomogram provided a high clinical benefit. CONCLUSION: A nomogram based on PVV provided an excellent preoperative prediction of PVST after splenectomy with esophagogastric devascularization.

The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence.

Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T. gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite's daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T. gondii.

Comparison of clinical outcomes following delivery of budesonide by both vibrating mesh nebulizer and jet nebulizer in premature infants with bronchopulmonary dysplasia.

Background: This study aimed to compare the efficacy of budesonide inhalation suspension administered via a vibrating mesh nebulizer vs. a jet nebulizer in the treatment of premature infants with bronchopulmonary dysplasia (BPD) undergoing high-frequency oscillatory ventilation (HFOV). Methods: Between July 2020 and July 2022, we retrospectively analyzed the medical records of 36 preterm infants diagnosed with BPD who underwent HFOV. Based on the nebulizer type used, infants were categorized into the vibrating mesh nebulizer group (VMN group) or the jet nebulizer group (JN group). Post-nebulization outcomes, such as the duration of mechanical ventilation, length of stay in the neonatal intensive care unit (NICU), ventilator-associated parameters, and arterial blood gas metrics, were compared between the two groups. Treatment-associated complications were also documented. Results: No significant differences were noted between the VMN and JN groups in terms of mechanical ventilation duration (p = 0.519), NICU length of stay (p = 0.112), ventilator-associated parameters, or complications (p = 0.700). However, after 2 weeks of treatment, the oxygenation index (p = 0.012) and arterial partial pressure of carbon dioxide (p = 0.006) were more favorable in the VMN group compared to the JN group. Conclusion: Among premature infants with BPD on HFOV, for administration of budesonide inhalation suspension resulted in an improved oxygenation index and reduced arterial partial pressure of carbon dioxide when compared to a jet nebulizer, indicating superior therapeutic efficacy.

Single-Frequency GNSS Integer Ambiguity Solving Based on Adaptive Genetic Particle Swarm Optimization Algorithm.

Carrier phase measurements currently play a crucial role in achieving rapid and highly accurate positioning of global navigation satellite systems (GNSS). Resolving the integer ambiguity correctly is one of the key steps in this process. To address the inefficiency and slow search problem during ambiguity solving, we propose a single-frequency GNSS integer ambiguity solving based on an adaptive genetic particle swarm optimization (AGPSO) algorithm. Initially, we solve for the floating-point solution and its corresponding covariance matrix using the carrier-phase double difference equation. Subsequently, we decorrelate it using the inverse integer Cholesky algorithm. Furthermore, we introduce an improved fitness function to enhance convergence and search performance. Finally, we combine a particle swarm optimization algorithm with adaptive weights to conduct an integer ambiguity search, where each generation selectively undergoes half-random crossover and mutation operations to facilitate escaping local optima. Comparative studies against traditional algorithms and other intelligent algorithms demonstrate that the AGPSO algorithm exhibits faster convergence rates, improved stability in integer ambiguity search results, and in practical experiments the baseline accuracy of the solution is within 0.02 m, which has some application value in the practical situation of short baselines.

Species diversity and related ecology of chiggers on small mammals in a unique geographical area of Yunnan Province, southwest China.

Chiggers are common ectoparasites and the exclusive vector of scrub typhus. Based on previous investigations from a unique geographical area in Yunnan Province of southwest China, the Three Parallel Rivers Area, we retrospectively studied the species diversity and related ecology of chiggers on rodents and other small mammals. A very high species diversity of 120 chigger species was identified. Five dominant chigger species accounted for 59.4% (5238/8965) of total chiggers, and among them Leptotrombidium scutellare is the second major vector of scrub typhus in China. Species diversity of the chigger community fluctuates greatly in different altitudinal and latitudinal gradients. There are significant differences in species composition, species diversity and dominant species of chiggers among hosts with apparent community heterogeneity. Based on the species abundance distribution, the expected total number of chigger species was estimated to be 170, 50 more than the number of actually collected species; this further indicates a very high chigger species diversity in this area. The bipartite ecological network analysis revealed the intricate relationships between chigger and host species-positive and negative correlations existed among some species of dominant and vector chiggers.