Exploring the preventive effects of Jie Geng Tang on pulmonary fibrosis induced in vitro and in vivo: a network pharmacology approach.

Pulmonary fibrosis is a debilitating lung disease marked by excessive fibrotic tissue accumulation, which significantly impairs respiratory function. Given the limitations of current therapies, there is an increasing interest in exploring traditional herbal formulations like Jie Geng Tang (JGT) for treatment. This study examines the potential of JGT and its bioactive component, quercetin, in reversing bleomycin (BLM)-induced pulmonary fibrosis in mice. We employed a BLM-induced MLE-12 cell damage model for in vitro studies and a bleomycin-induced fibrosis model in C57BL/6 mice for in vivo experiments. In vitro assessments showed that JGT significantly enhanced cell viability and reduced apoptosis in MLE-12 cells treated with BLM. These findings underscore JGT's potential for cytoprotection against fibrotic agents. In vivo, JGT was effective in modulating the expression of E-cadherin and vimentin, key markers of the epithelial-mesenchymal transition (EMT) pathway, indicating its role in mitigating EMT-associated fibrotic changes in lung tissue. Quercetin, identified through network pharmacology analysis as a potential key bioactive component of JGT, was highlighted for its role in the regulatory mechanisms underlying fibrosis progression, particularly through the modulation of the IL-17 pathway and Il6 expression. By targeting inflammatory pathways and key processes like EMT, JGT and quercetin offer a potent alternative to conventional therapies, meriting further clinical exploration to harness their full therapeutic potential in fibrotic diseases.

SlWRKY37 targets SlLEA2 and SlABI5-like7 to regulate seed germination vigor in tomato.

Seed germination is a critical phase for the life cycle and propagation of higher plants. This study explores the role of SlWRKY37, a WRKY transcription factor in tomato, in modulating seed germination. We discovered that SlWRKY37 expression is markedly downregulated during tomato seed germination. Through CRISPR/Cas9-mediated editing, we demonstrate that SlWRKY37 knockout enhances germination, while its overexpression results in a delay compared to the wild type. Transcriptome analysis revealed 679 up-regulated and 627 down-regulated genes in Slwrky37-CRISPR deletion mutants relative to the wild type. Gene ontology (GO) enrichment analysis indicated these differentially expressed genes are linked to seed dormancy, abscisic acid homeostasis, and protein phosphorylation pathways. Bioinformatics and biochemical assays identified SlABI5-like7 and SlLEA2 as key transcriptional targets of SlWRKY37, integral to tomato seed dormancy regulation. Additionally, SlWRKY37 was found to be post-translationally phosphorylated at Ser65, a modification crucial for its transcriptional activation. Our findings elucidate the regulatory role of SlWRKY37 in seed dormancy, suggesting its potential as a target for gene editing to reduce seed dormancy in tomato breeding programs.

Stable gullies provide a suitable habitat for functional insects and reduce the threat of pests on crops in farmland of Northeast China.

Gullies with lower altitudes compared to the surrounding environment are widely distributed in farmland of the watershed and their numbers are still expanding. However, it is still unclear how these gullies regulate the functional insects in farmland. In this study, land use types combined with the herbaceous plant, herbicide application, soil moisture, topography and climatic factors during crop growth were considered to understand how gullies influence the dynamics of functional insects in farmland from a watershed (240 ha) of Northeast China. The primary findings demonstrate that the richness and abundance of functional insects are generally greatest in gullies, particularly in stable gullies, and decrease in the following order: forest belts, grasslands, and farmlands within the watershed. Notably, the ratios of beneficial insects to pests (BI/Pest) in terms of richness and abundance were lower in gullies before July but reversed after July, in comparison to farmland. Stable gullies exhibited higher BI/Pest abundance and diversity ratios than developing gullies. The richness and abundance of functional insects were higher in the middle sections of gullies compared to their heads and tails. Furthermore, the ratios of BI/Pest were generally lower in farmlands than in any gully position. Functional insect dynamics were mainly determined by season, followed by plant abundance and biomass in the gullies, and rarely by soil moisture in the both watershed and single gullies scales. Generally, the richness and abundance of functional insects in farmland were mainly influenced by gullies, especially influenced by the gully middle position. Insect composition in farmland influenced by stable gullies was stronger than by developing gullies, and stable gullies were more beneficial in reducing the threat of pests to crops in the farmland of the watershed.

Selenium restored mitophagic flux to alleviate cadmium-induced hepatotoxicity by inhibiting excessive GPER1-mediated mitophagy activation.

Cadmium (Cd) is a common environmental pollutant, while selenium (Se) can ameliorate heavy metal toxicity. Consequently, this study aimed to investigate the protective effects of Se against Cd-induced hepatocyte injury and its underlying mechanisms. To achieve this, we utilized the Dongdagou-Xinglong cohort, BRL3A cell models, and a rat model exposed to Cd and/or Se. The results showed that Se counteracted liver function injury and the decrease in GPER1 levels caused by environmental Cd exposure, and various methods confirmed that Se could protect against Cd-induced hepatotoxicity both in vivo and in vitro. Mechanistically, Cd caused excessive mitophagy activation, evidenced by the colocalization of LC3B, PINK1, Parkin, P62, and TOMM20. Transfection of BRL3A cells with mt-keima adenovirus indicated that Cd inhibited autophagosome-lysosome fusion, thereby impeding mitophagic flux. Importantly, G1, a specific agonist of GPER1, mitigated Cd-induced mitophagy overactivation and hepatocyte toxicity, whereas G15 exacerbates these effects. Notably, Se supplementation attenuated Cd-induced GPER1 protein reduction and excessive mitophagy activation while facilitating autophagosome-lysosome fusion, thereby restoring mitophagic flux. In conclusion, this study proposed a novel mechanism whereby Se alleviated GPER1-mediated mitophagy and promoted autophagosome-lysosome fusion, thus restoring Cd-induced mitophagic flux damage, and preventing hepatocyte injury.

Modular Access to Functionalized Oxetanes as Benzoyl Bioisosteres.

Bioisosterism is a valuable principle exploited in drug discovery to fine-tune physicochemical properties of bioactive compounds. Functionalized 3-aryl oxetanes, as an important class of bioisosteres for benzoyl groups (highly prevalent structures in approved drugs), have been rarely utilized in agrochemicals and pharmaceuticals due to significant synthetic challenges. Here, we present a modular synthetic strategy based on the unexplored yet readily available reagents, oxetanyl trichloroacetimidates, inspired by Schmidt glycosylation, enabling easy access to a library of functionalized oxetanes. This operationally simple protocol leverages the vast existing libraries of aryl halides and various nucleophiles. The power and generality of this approach is demonstrated by late-stage functionalization of complex molecules, as well as the rapid synthesis of oxetane analogues of bioactive molecules and marketed drugs. Preliminary mechanistic study suggests that the oxygen atom in the oxetane ring plays a crucial role in stabilizing the carbocation intermediates.

Gastrodin relieves Parkinson's disease-related motor deficits by facilitating the MEK-dependent VMAT2 to maintain dopamine homeostasis.

BACKGROUND: Dysfunction of dopamine homeostasis (DAH), which is regulated by vesicular monoamine transporter 2 (VMAT2), is a vital cause of dopamine (DA) neurotoxicity and motor deficits in Parkinson's disease (PD). Gastrodin (4-hydroxybenzyl alcohol 4-O-ß-D-glucoside; GTD), a natural active compound derived from Gastrodia elata Blume, can be used to treat multiple neurological disorders, including PD. However, whether GTD regulates VMAT2-mediated DAH dysfunction in PD models remains unclear. PURPOSE: To explore whether GTD confers dopaminergic neuroprotection by facilitating DA vesicle storage and maintaining DAH in PD models. METHODS: Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and PC12 cells with 1-methyl-4-phenyl-pyridinium (MPP+) to induce PD characteristics. Multiple behavioural tests were performed to evaluate the motor functions of the mice. HPLC was used to measure DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. Transmission electron microscopy was used to observe synaptic vesicles. Molecular docking and molecular dynamics were used to determine the binding affinity of GTD to the target protein. Reserpine (Res, a VMAT2 inhibitor) and PD0325901 (901, a MEK inhibitor) were employed to investigate the mechanism of GTD. Western blotting and immunohistochemistry were used to assess the expression of the target proteins. RESULTS: GTD attenuated motor deficits and dopaminergic neuronal injury, reversed the imbalance of DAH, and increased VMAT2 levels and vesicle volume in MPTP-induced mice. GTD ameliorated cell damage, ROS release, and dysfunction of DAH in MPP+-induced PC12 cells. Moreover, the neuroprotective effects of GTD were reversed by Res in vitro and in vivo. Furthermore, GTD can activate the MEK/ERK/CREB pathway to upregulate VMAT2 in vitro and in vivo. Interestingly, 901 reversed the effects of GTD on VMAT2 and dopaminergic neuronal impairment. CONCLUSION: GTD relieved PD-related motor deficits and dopaminergic neuronal impairment by facilitating MEK-depended VMAT2 to regulate DAH, which offers new insights into its therapeutic potential.

Knowledge and attitude toward postoperative antithrombotic management and prevention in patients with coronary revascularization: a cross-sectional study.

Background: This study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization. Methods: This cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire. Results: This study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0-26) and 43.68 ± 6.01 (range: 21-50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P = 0.035), high school or technical school education (OR = 2.356, P = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P = 0.002), BMI ≥ 24.0 kg/m2 (OR = 0.372, P = 0.011), junior high school (OR = 3.699, P = 0.002), high school or technical school (OR = 2.903, P = 0.028), high associate degree or above education (OR = 6.068, P = 0.014), monthly average income 3,000-5,000 RMB (OR = 0.296, P = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P = 0.021), with hypertension (OR = 0.333, P = 0.003), blood tests every 2-3 weeks (OR = 10.811, P = 0.011), blood tests every month (OR = 4.221, P = 0.024), and blood tests every 2-3 months (OR = 3.342, P = 0.033) were independently associated with attitude. Conclusion: CAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes.

N-Carbamylglutamate in ovo feeding improves carcass yield, muscle fiber development, and meat quality in broiler chickens.

BACKGROUND: Insufficient endogenous nutrients in the broiler embryo can lead to muscle gluconeogenesis, which ultimately affects the post-hatching performance of chicks. This study investigated the effects of in ovo feeding (IOF) of N-carbamylglutamate (NCG) on the growth hormones, carcass yield, and meat quality in broilers. Fertile eggs from a 30-week-old Ross 308 breeder flock were divided into three treatment groups: NC (non-injection), SC (100 µL saline-injection), and NCG (2 mg NCG injection). Each group had six replicates, with 70 eggs per replicate during incubation. Injections were administered on the 17.5th day of embryonic development. After hatching, 270 chicks were selected for 42-day rearing for further sampling. RESULTS: Chicks in the NCG group had significantly higher body weight (BW) and average daily gain (ADG) at the growing phase, increased growth and testosterone hormone in both feeding phases (21 and 42 days), and improved average daily gain (ADG) and food conversion ratio (FCR) in both grower and entire feeding phases (P < 0.05). Triiodothyronine (T3) and tetraiodothyronine (T4) levels, carcass yield, dressing, drum weight, breast muscle weight, drumstick weights, thighs, pectoralis major, and their part percentage of carcass were improved in the NCG group (P < 0.05), these effects were varied along feeding phases. Moreover, IOF of the NCG also improved pectoralis breast muscle color values at 24 h post mortem (P < 0.05). CONCLUSION: These results suggest that NCG injection at the late embryonic age of broiler enhances growth performance and meat quality throughout the lifespan and this can probably be attributed to an increase in thyroid and testosterone hormones, indicating potential involvement in metabolic and nutrient partitioning pathway regulation. © 2024 Society of Chemical Industry.

Laser Additive Manufacturing of Three-Dimensional Ti/TiN Nanotube Arrays with Hierarchical Pore Structures and Promoted Supercapacitor Performances.

Titanium-based composites hold great promise in versatile functional application fields, including supercapacitors. However, conventional subtractive methods for preparing complex-shaped titanium-based composites generally suffer from several significant shortcomings, including low efficiency, strictly simple geometry, low specific surface area, and poor electrochemical performance of the products. Herein, three-dimensional composites of Ti/TiN nanotube arrays with hierarchically porous structures were prepared using the additive manufacturing method of selective laser melting combined with anodic oxidation and nitridation. The resultant Ti/TiN nanotube array composites exhibit good electrical conductivity, ultrahigh specific surface areas, and outstanding supercapacitor performances featuring the unique combination of a large specific capacitance of 134.4 mF/cm2 and a high power density of 4.1 mW/cm2, which was remarkably superior to that of their counterparts. This work is anticipated to provide new insights into the facile and efficient preparation of high-performance structural and functional devices with arbitrarily complex geometries and good overall performances.

DeforT: Deformable transformer for visual tracking.

Most trackers formulate visual tracking as common classification and regression (i.e., bounding box regression) tasks. Correlation features that are computed through depth-wise convolution or channel-wise multiplication operations are input into both the classification and regression branches for inference. However, this matching computation with the linear correlation method tends to lose semantic features and obtain only a local optimum. Moreover, these trackers use an unreliable ranking based on the classification score and the intersection over union (IoU) loss for the regression training, thus degrading the tracking performance. In this paper, we introduce a deformable transformer model, which effectively computes the correlation features of the training and search sets. A new loss called the quality-aware focal loss (QAFL) is used to train the classification network; it efficiently alleviates the inconsistency between the classification and localization quality predictions. We use a new regression loss called α-GIoU to train the regression network, and it effectively improves localization accuracy. To further improve the tracker's robustness, the candidate object location is predicted by using a combination of online learning scores with a transformer-assisted framework and classification scores. An extensive experiment on six testing datasets demonstrates the effectiveness of our method. In particular, the proposed method attains a success score of 71.7% on the OTB-2015 dataset and an AUC score of 67.3% on the NFS30 dataset, respectively.

Mental health problems of front-line medical staff in the early stage of public health emergencies.

In the face of the unprecedented public health crisis caused by the novel coronavirus pneumonia epidemic, front-line health workers are under enormous mental pressure. This paper aims to explore the mental health challenges faced by front-line health workers in the early stages of a public health emergency, such as stress, anxiety, and depression. At the same time, the factors that increase their mental stress are analyzed, and practical measures are put forward to prevent and manage mental health problems, aiming at improving the quality of medical treatment during public health emergencies. This paper has some reference value for people engaged in mental health prevention.

Light-induced giant enhancement of nonreciprocal transport at KTaO3-based interfaces.

Nonlinear transport is a unique functionality of noncentrosymmetric systems, which reflects profound physics, such as spin-orbit interaction, superconductivity and band geometry. However, it remains highly challenging to enhance the nonreciprocal transport for promising rectification devices. Here, we observe a light-induced giant enhancement of nonreciprocal transport at the superconducting and epitaxial CaZrO3/KTaO3 (111) interfaces. The nonreciprocal transport coefficient undergoes a giant increase with three orders of magnitude up to 105 A-1 T-1. Furthermore, a strong Rashba spin-orbit coupling effective field of 14.7 T is achieved with abundant high-mobility photocarriers under ultraviolet illumination, which accounts for the giant enhancement of nonreciprocal transport coefficient. Our first-principles calculations further disclose the stronger Rashba spin-orbit coupling strength and the longer relaxation time in the photocarrier excitation process, bridging the light-property quantitative relationship. Our work provides an alternative pathway to boost nonreciprocal transport in noncentrosymmetric systems and facilitates the promising applications in opto-rectification devices and spin-orbitronic devices.

Nationwide distribution of perfluoroalkyl ether carboxylic acids in Chinese diets: An emerging concern.

With the phase-out of perfluorooctanoic acid (PFOA) and its replacement by perfluoroalkyl ether carboxylic acids (PFECAs), there is a potential for increased exposure to various new PFECAs among the general population in China. While there are existing studies on dietary exposure to legacy perfluoroalkyl and polyfluoroalkyl substances (PFASs), research on dietary exposure to PFECAs, especially among the general Chinese populace, remains scarce. In the present study, we investigated the distribution of PFECAs in dietary sources from 33 cities across five major regions in China, along with the associated dietary intake. Analysis indicated that aquatic animal samples contained higher concentrations of legacy PFASs compared to those from terrestrial animals and plants. In contrast, PFECAs were found in higher concentrations in plant and terrestrial animal samples. Notably, hexafluoropropylene oxide dimer (HFPO-DA) was identified as the dominant compound in vegetables, cereals, pork, and mutton across the five regions, suggesting widespread dietary exposure. PFECAs constituted the majority of PFAS intake (57 %), with the estimated daily intake (EDI) of HFPO-DA ranging from 2.33 to 3.96 ng/kg bw/day, which corresponds to 0.78-1.32 times the reference dose (RfD) (3.0 ng/kg bw/day) set by the United States Environmental Protection Agency. Given the ubiquity of HFPO-DA and many other PFECAs in the nationwide diet of China, there is an urgent need for further research into these chemicals to establish relevant safety benchmarks or consumption advisory values for the diet.

Histological and molecular difference in albumen quality between post-adolescent hens and aged hens.

The decline in albumen quality resulting from aging hens poses a threat to the financial benefits of the egg industry. Exploring the underlying mechanisms from the perspective of cell molecules of albumen formation is significant for the efficient regulation of albumen quality. Two individual groups of Hy-Line Brown layers with ages of 40 (W40) and 100 (W100) wk old were used in the present study. Each group contained over 2,000 birds. This study assessed the egg quality, biochemical indicators and physiological status of hens between W40 and W100. Subsequently, a quantitative proteomic analysis was conducted to identify differences in protein abundance in magnum tissues between W40 and W100. In the W40 group, significant increases (P < 0.05) were notable for albumen quality (thick albumen solid content, albumen height, Haugh unit), serum indices (calcium, estrogen, and progesterone levels), magnum histomorphology (myosin light-chain kinase content, secretory capacity, mucosal fold, goblet cell count and proportion) as well as the total antioxidant capacity of the liver. However, the luminal diameter of the magnum, albumen gel properties and random coil of the albumen were increased (P < 0.05) in the W100 group. The activity of glutathione, superoxidase dismutase, and malondialdehyde in the liver, magnum, and serum did not vary (P > 0.05) among the groups. Proteomic analysis revealed the identification of 118 differentially expressed proteins between the groups, which comprised proteins associated with protein secretion, DNA damage and repair, cell proliferation, growth, antioxidants, and apoptosis. Furthermore, Kyoto Encyclopedia of Genes pathway analysis revealed that BRCA2 and FBN1 were significantly downregulated in Fanconi anemia (FA) and TGF-ß signaling pathways in W100, validated through quantitative real-time PCR (qRT-PCR). In conclusion, significant age-related variations in albumen quality, and magnum morphology are regulated by proteins involved in antioxidant capacity.

Global vaccine coverage and childhood survival estimates: 1990-2019.

Objective: To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019. Methods: We used child mortality and vaccine coverage data from the Global Burden of Disease Study. We used a modified child survival framework and applied a mixed-effects regression model to estimate the reduction in deaths in children younger than 5 years associated with eight vaccines. Findings: Between 1990 and 2019, the diphtheria-tetanus-pertussis (DTP), measles, rotavirus and Haemophilus influenzae type b vaccines were significantly associated with an estimated 86.9 (95% confidence interval, CI: 57.2 to 132.4) million fewer deaths in children younger than 5 years worldwide. This decrease represented a 24.2% (95% CI: 19.8 to 28.9) reduction in deaths relative to a scenario without vaccines. The DTP and measles vaccines averted 46.7 (95% CI: 30.0 to 72.7) million and 37.9 (95% CI: 25.4 to 56.8) million deaths, respectively. Of the total reduction in child mortality associated with vaccines, 84.2% (95% CI: 83.0 to 85.1) occurred in 73 countries supported by Gavi, the Vaccine Alliance, with an estimated 45.4 (95% CI: 29.8 to 69.2) million fewer deaths from 2000 to 2019. The largest reductions in deaths associated with these four vaccines were in India, China, Ethiopia, Pakistan and Bangladesh (in order of the size of reduction). Conclusion: Vaccines continue to reduce childhood mortality significantly, especially in Gavi-supported countries, emphasizing the need for increased investment in routine immunization programmes.

Quantifying Contributions of Different Repulsion to Film Drainage Time during the Bubble-Solid Surface Attachment and Implications for the Flotation of Fine Particles.

The flotation recovery of fine particles faces serious challenges due to the lack of kinetic energy required for supporting their radial displacement and attachment with bubbles. Generally, the hydrodynamic resistance and repulsive disjoining pressure successively inhibit the liquid outflow intervening between the bubble and solid surfaces. To quantitatively characterize the influence of the main repulsion on film thinning time, experiments have been designed in three different aqueous systems. Bubble surface mobility closely associated with hydrodynamic resistance was determined by the rising bubble technique, and the DLVO theory was employed to confirm the evolution of electrostatic repulsion. The film drainage process was then measured based on the high-speed microscopic interferometry. Furthermore, the influence of the main repulsion on bubble-solid surface interactions was examined by flotation recovery. Results show that the earlier buildup of hydrodynamic force ran through the whole film thinning process, and under immobile conditions, the central region gradually became dominant in film thinning due to the very limited fluid flow at the thinnest rim position. Therefore, to achieve the identical film thickness (∼100 nm), the large hydrodynamic resistance could prolong the film thinning time by about 1 order of magnitude, compared with that induced by electrostatic repulsion, which accounts for the increased flotation recovery by 10% using mobile bubbles. This study not only enhances the understanding of how typical repulsive forces work in film drainage dynamics but also opens up an avenue for enhancing flotation and avoiding wasting resources by modulating bubble surface mobility and thus micro/nanoscale fluid flow.

Concentrations and influencing factors of 17 elements in placenta, cord blood, and maternal blood of women from an e-waste recycling area.

BACKGROUND: The effects of prenatal element exposure on mothers and fetuses have generated concern. Profiles of trace and toxic elements in biological material are urgently desired, especially for women who reside near e-waste recycling facilities. The aim of this study was to investigate elements concentrations in placenta, cord blood, and maternal blood of women and to evaluate the influencing factors. METHODS: A group of 48 women from an e-waste recycling site and a group of 31 women from a non-e-waste recycling site were recruited. Basic characteristics were collected by questionnaire and the concentrations of 17 elements in placenta, cord blood, and maternal blood samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Finally, the generalized linear model regression analysis (GLM) was used to test the association between element concentrations and possible factors. RESULTS: Compared to the control group, the exposed group had significantly elevated cadmium (Cd), zinc (Zn), nickel (Ni), and antimony (Sb) in placenta, and higher lead (Pb) in maternal blood and cord blood (P<0.05). Sb concentration in maternal blood was significantly lower than in the control group (P<0.05). GLM analysis showed that element concentrations were mainly associated with maternal age [chromium (Cr), iron (Fe), selenium (Se), cobalt (Co), mercury (Hg) in placenta, copper (Cu) in maternal blood], education (Se, Sb in placenta), family income (Cu in maternal blood and Ni in placenta), passive smoking [Cu and Zn in placenta, Pb in maternal blood], and e-waste contact history (Hg in cord blood, Cu, Zn, and Cd in maternal blood). CONCLUSIONS: Women in the e-waste recycling area had higher toxic element levels in the placenta and blood samples. More preventive measures were needed to reduce the risk of element exposure for mothers and fetuses in these areas.

The Impact of SARS-CoV-2 Infection on the Length of Stay in the Neuro-ICU:A Prospective Multicenter Cohort Study in Eight Neuro-ICU, China Between February and April 2023.

Purpose: The SARS-CoV-2 infection cases are increasing rapidly in neuro-intensive care units (neuro-ICUs) at the beginning of 2023 in China. We aimed to characterize the prevalence, risk factors, and prognosis of critically ill patients treated in neuro-ICUs. Materials and Methods: In the prospective, multicenter, observational registry study, critically ill patients with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and traumatic brain injury (TBI) admitted to eight Chinese neuro-ICUs between Feb 16, 2023, to Apr 30, 2023 were enrolled for the study. Mortality and ICU stay day were used as the primary outcomes. Results: 131 patients were finally included and analyzed (mean age 60.36 years [SD 13.81], 64.12% male, 39.69% SARS-CoV-2 infected). The mortality is higher in the SARS-CoV-2 infection group without statistical signification (7.69% vs 5.06%, p>0.05). The length of stay (LOS) in neuro-ICUs was significantly longer among the SARS-CoV-2 infection patients (7(1-12) vs 4(1-8), p<0.01), with increased viral pneumonia occurrence (58.54% vs 7.32%, p<0.01). SARS-CoV-2 infection, surgery, and low GCS scores were independent risk factors for prolonged LOS, and respiratory/renal failure were independent risk factors for death. Conclusion: Based on the present neuro-ICU cohort, SARS-CoV-2 infection was a significant risk for the prolonged LOS of neuro-critically ill patients. Trial Registration: Registered with Chictr.org.cn (ChiCTR2300068355) at 16 February 2023, Prospective registration. https://www.chictr.org.cn/showproj.html?proj=188252.

Decreased eggshell strength caused by impairment of uterine calcium transport coincide with higher bone minerals and quality in aged laying hens.

BACKGROUND: Deteriorations in eggshell and bone quality are major challenges in aged laying hens. This study compared the differences of eggshell quality, bone parameters and their correlations as well as uterine physiological characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction. A total of 240 74-week-old Hy-line Brown laying hens were selected and allocated to a high (HBS, 44.83 ± 1.31 N) or low (LBS, 24.43 ± 0.57 N) eggshell breaking strength group. RESULTS: A decreased thickness, weight and weight ratio of eggshells were observed in the LBS, accompanied with ultrastructural deterioration and total Ca reduction. Bone quality was negatively correlated with eggshell quality, marked with enhanced structures and increased components in the LBS. In the LBS, the mammillary knobs and effective layer grew slowly. At the initiation stage of eggshell calcification, a total of 130 differentially expressed genes (DEGs, 122 upregulated and 8 downregulated) were identified in the uterus of hens in the LBS relative to those in the HBS. These DEGs were relevant to apoptosis due to the cellular Ca overload. Higher values of p62 protein level, caspase-8 activity, Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the LBS. TUNEL assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the LBS. Although few DEGs were identified at the growth stage, similar uterine tissue damages were also observed in the LBS. The expressions of runt-related transcription factor 2 and osteocalcin were upregulated in humeri of the LBS. Enlarged diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the HBS. CONCLUSION: The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages, which could affect eggshell calcification and lead to a weak ultrastructure. Impaired uterine Ca transport may result in reduced femoral bone resorption and increased humeral bone formation to maintain a higher mineral and bone quality in the LBS.

Influenza A Virus PB1-F2 Induces Affective Disorder by Interfering Synaptic Plasticity in Hippocampal Dentate Gyrus.

Influenza A virus (IAV) infection, which leads to millions of new cases annually, affects many tissues and organs of the human body, including the central nervous system (CNS). The incidence of affective disorders has increased after the flu pandemic; however, the potential mechanism has not been elucidated. PB1-F2, a key virulence molecule of various influenza virus strains, has been shown to inhibit cell proliferation and induce host inflammation; however, its role in the CNS has not been studied. In this study, we constructed and injected PB1-F2 into the hippocampal dentate gyrus (DG), a region closely associated with newborn neurons and neural development, to evaluate its influence on negative affective behaviors and learning performance in mice. We observed anxiety- and depression-like behaviors, but not learning impairment, in mice injected with PB1-F2. Furthermore, pull-down and mass spectrometry analyses identified several potential PB1-F2 binding proteins, and enrichment analysis suggested that the most affected function was neural development. Morphological and western blot studies revealed that PB1-F2 inhibited cell proliferation and oligodendrocyte development, impaired myelin formation, and interfered with synaptic plasticity in DG. Taken together, our results demonstrated that PB1-F2 induces affective disorders by inhibiting oligodendrocyte development and regulating synaptic plasticity in the DG after IAV infection, which lays the foundation for developing future cures of affective disorders after IAV infection.