Influenza A virus infection disrupts the function of syncytiotrophoblast cells and contributes to adverse pregnancy outcomes.

Pregnancy heightens susceptibility to influenza A virus (IAV) infection, thereby increasing the risk of severe pneumonia and maternal mortality. It also raises the chances of adverse outcomes in offspring, such as fetal growth restriction, preterm birth, miscarriage, and stillbirth in offsprings. However, the underlying mechanisms behind these effects remain largely unknown. Syncytiotrophoblast cells, crucial in forming the placental barrier, nutrient exchange and hormone secretion, have not been extensively studied for their responses to IAV. In our experiment, we used Forskolin-treated BeWo cells to mimic syncytiotrophoblast cells in vitro, and infected them with H1N1, H5N1 and H7N9 virus stains. Our results showed that syncytiotrophoblast cells, with their higher intensity of sialic acid receptors, strongly support IAV infection and replication. Notably, high-dose viral infection and prolonged exposure resulted in a significant decrease in fusion index, as well as gene and protein expression levels associated with trophoblast differentiation, ß-human chorionic gonadotropin secretion, estrogen and progesterone biosynthesis, and nutrient transport. In pregnant BALB/c mice infected with the H1N1 virus, we observed significant decreases in trophoblast differentiation and hormone secretion gene expression levels. IAV infection also resulted in preterm labor, fetal growth restriction, and increased maternal and fetal morbidity and mortality. Our findings indicate that IAV infection in syncytiotrophoblastic cells can result in adverse pregnancy outcomes by altering trophoblast differentiation, suppressing of ß-hCG secretion, and disrupting placental barrier function.

Deoxygenating Reduction of CO2 by [Cp*Al]4 to Form a (Al3O2C)2 Cluster Featuring Two Ketene Moieties.

Herein we report that the reaction of the low-valent aluminum(I) species [Cp*Al]4 (Cp* = pentamethylcyclopentadienyl) with CO2 exhibits complete cleavages of the C═O bonds. The deoxygenating reduction reaction of [Cp*Al]4 with CO2 at 120 °C afforded [(Cp*)3Al3O2C(CO)]2 (1), which featured two stacked (Al3O2C)2 units and two C═C═O ketene moieties. Moreover, the isoelectronic analogues of diimine and isothiocyanate with CO2 were also investigated, and the reactions of [Cp*Al]4 with Dipp*-N═C═N-Dipp* and Dipp-C═N═S [Dipp* = 2,6-bis(diphenylmethyl)-4-tert-butylphenyl; Dipp = 2,6-diisopropylphenyl] afforded dialuminylimine (2) and tetrameric [Cp*AlS]4 (3), respectively.

[Effect of Pien Tze Huang against EV71].

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.

The M2 Protein of the Influenza A Virus Interacts with PEX19 to Facilitate Virus Replication by Disrupting the Function of Peroxisome.

The peroxisomal biogenesis factor 19 (PEX19) is necessary for early peroxisomal biogenesis. PEX19 has been implicated in the replication of a variety of viruses, but the details pertaining to the mechanisms of how PEX19 engages in the life cycle of these viruses still need to be elucidated. Here, we demonstrated that the C terminus of PEX19 interacted with the cytoplasmic tail region of the M2 protein of the influenza A virus (IAV) and inhibited the viral growth titers. IAV infection or PEX19 knockdown triggered a reduction in the peroxisome pool and led to the accumulation of ROS and cell damage, thereby creating favorable conditions for IAV replication. Moreover, a reduction in the peroxisome pool led to the attenuation of early antiviral response mediated by peroxisome MAVS and downstream type III interferons. This study also showed that the interaction between IAV M2 and PEX19 affected the binding of PEX19 to the peroxisome-associated protein PEX14 and peroxisome membrane protein 24 (PMP24). Collectively, our data demonstrate that host factor PEX19 suppresses the replication of the IAV, and the IAV employs its M2 protein to mitigate the restricting role of PEX19.

Does pasteurization inactivate bird flu virus in milk?

Recently, an outbreak of highly pathogenic avian influenza A (H5N1), which carries the clade 2.3.4.4b hemagglutinin (HA) gene and has been prevalent among North American bird populations since the winter of 2021, was reported in dairy cows in the United States. As of 24 May 2024, the virus has affected 63 dairy herds across nine states and has resulted in two human infections. The virus causes unusual symptoms in dairy cows, including an unexpected drop in milk production, and thick colostrum-like milk. Notably, The US Food and Drug Administration reported that around 20% of tested retail milk samples contained H5N1 viruses, with a higher percentage of positive results from regions with infected cattle herds. Data are scant regarding how effectively pasteurization inactivates the H5N1 virus in milk. Therefore, in this study, we evaluated the thermal stability of the H5 clade 2.3.4.4b viruses, along with one human H3N2 virus and other influenza subtype viruses, including H1, H3, H7, H9, and H10 subtype viruses. We also assessed the effectiveness of pasteurization in inactivating these viruses. We found that the avian H3 virus exhibits the highest thermal stability, whereas the H5N1 viruses that belong to clade 2.3.4.4b display moderate thermal stability. Importantly, our data provide direct evidence that the standard pasteurization methods used by dairy companies are effective in inactivating all tested subtypes of influenza viruses in raw milk. Our findings indicate that thermally pasteurized milk products do not pose a safety risk to consumers.

Tailoring a Hybrid Functional Layer for Mg Metal Anodes in Conventional Electrolytes with a Low Overpotential.

The development of high-voltage Mg metal batteries is hampered by the incompatibility between a Mg metal anode and conventional electrolyte, leading to a high overpotential for Mg plating/stripping processes. In this work, we tailored a hybrid functional layer consisting of Bi/MgCl2/polytetrahydrofuran (PTHF) by an in situ THF polyreaction during the reaction of the Mg anode with BiCl3 solution. The introduction of PTHF inhibits the growth of Bi particles and fills the layer interstice with MgCl2-containing PTHF, improving the structural integrity of the functional layer and insulation between the electrolyte and Mg anode. As a result, compared to a simply modified Bi/MgCl2 layer, the Bi/MgCl2/PTHF functional layer exhibits a lower polarization voltage of 0.25 V and longer cycling life of more than 2000 h at 0.1 mA cm-2. Mechanism analysis shows that Mg is plated on the surface of Bi particles within the layer. The Mo6S8/Mg full battery with the hybrid functional layer achieved a low voltage hysteresis of ∼0.25 V and long cycling life over 500 cycles at 50 mA g-1. This work provides a facile and effective hybrid functional layer strategy to realize Mg metal batteries in conventional electrolytes.

Modification of a Cu Mesh with Nanowires and Magnesiophilic Ag Sites to Induce Uniform Magnesium Deposition.

The nature of dendrite-free magnesium (Mg) metal anodes is an important advantage in rechargeable magnesium batteries (RMBs). However, this traditional cognition needs to be reconsidered due to inhomogeneous Mg deposits under extreme electrochemical conditions. Herein, we report a three-dimensional (3D) Cu-based host with magnesiophilic Ag sites (denoted as "Ag@3D Cu mesh") to regulate Mg deposition behaviors and achieve uniform Mg electrodeposition. Mg deposition/stripping behaviors are obviously improved under the cooperative effect of nanowire structures and Ag sites. The test results indicate that nucleation overpotentials are reduced distinctly and cycling performances are prolonged, suggesting that the general rules of 3D structures and affinity sites improve the durability and reversibility of Mg deposition/stripping. Besides, a unique concave surface structure can induce Mg to deposit into the interior of the interspace, which utilizes Mg more efficiently and leads to improved electrochemical performances with limited Mg content. Furthermore, in situ optical microscopic images show that the Ag@3D Cu mesh can attain a smooth surface, nearly without Mg protrusions, under 8.0 mA cm-2, which prevents premature short circuits. This report is a pioneering work to demonstrate the feasibility of modification of Cu-based current collectors and the necessity of functional current collectors to improve the possibility of practical applications for RMBs.

Ultralong-Lifespan Magnesium Batteries Enabled by the Synergetic Manipulation of Oxygen Vacancies and Electronic Conduction.

As a potential next-generation energy storage system, rechargeable magnesium batteries (RMBs) have been receiving increasing attention due to their excellent safety performance and high energy density. However, the sluggish kinetics of Mg2+ in the cathode has become one of the main bottlenecks restricting the development of RMBs. Here, we introduce oxygen vacancies to spherical NaV6O15 cross-linked with carbon nanotubes (CNTs) (denoted as SNVOX-CNT) as a cathode material to achieve an impressive long-term cycle life of RMBs. The introduction of oxygen vacancies can improve the electrochemical performance of the NaV6O15-X cathode material. Besides, owing to the introduction of CNTs, excellent internal/external electronic conduction paths can be built inside the whole electrode, which further achieves excellent electrochemical performance. Moreover, such a unique structure can efficiently improve the diffusion kinetics of Mg2+ (ranging from 1.28 × 10-12 to 7.21 × 10-12 cm2·s-1). Simulation calculations further prove that oxygen vacancies can cause Mg2+ to be inserted in NaV6O15-X. Our work proposes a strategy for the synergistic effect of oxygen vacancies and CNTs to improve the diffusion coefficient of Mg2+ in NaV6O15 and enhance the electrochemical performance of RMBs.

Pien Tze Huang accelerated wound healing by inhibition of abnormal fibroblast apoptosis in Streptozotocin induced diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic foot ulcer is one of the most serious complications of diabetes. Effective medical treatment regarding improvement of ulcer healing in patients is essential. Pien Tze Huang (PZH), a valuable Chinese traditional medicine, has been found significant efficacy on the curing of diabetic wound in clinic recently. AIM OF THE STUDY: This work was conducted to confirm the efficacy, and compare the therapeutic effect through the oral administration and local delivery route, providing a rationale for the new PZH form development; besides, the mechanisms through which PZH promoted the wound healing was also discussed. MATERIALS AND METHODS: First, the chemical composition of PZH was characterized by 1H-NMR and HPLC. The anti-apoptosis effects of PZH on high concentration glucose injured epidermal fibroblast (HFF-1) was investigated in a dose dependent way. Then, the effects of the systematical administration of PZH, and the topical used route on excisional wounds of Streptozotocin (STZ) induced diabetic mice were compared. RESULTS: The results illustrated that PZH decreased the reactive oxygen species (ROS) levels in cells, preventing cell damage/apoptosis through an ROS/Bcl-2/Bax/Caspase-3 pathway. The in vivo study proved that topical use of PZH exceeded the systematical route both in accelerating the wound closure and improving the healing quality. Meanwhile, PZH promoted wound closure through stimulating the secretion of Col-I, decreasing fibroblast apoptosis, and enhancing myo-fibroblast differentiation, in consistent with the mechanism study in vitro. CONCLUSIONS: Local used PZH improves wound healing by inhibiting the abnormal HFF-1 apoptosis and senescence. The study held a great promise for development of a topical dosage form of PZH for diabetic wound healing.