Disruption of pulmonary microvascular endothelial barrier by dysregulated claudin-8 and claudin-4: uncovered mechanisms in porcine reproductive and respiratory syndrome virus infection.

The pulmonary endothelium is a dynamic and metabolically active monolayer of endothelial cells. Dysfunction of the pulmonary endothelial barrier plays a crucial role in the acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), frequently observed in the context of viral pneumonia. Dysregulation of tight junction proteins can lead to the disruption of the endothelial barrier and subsequent leakage. Here, the highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) served as an ideal model for studying ALI and ARDS. The alveolar lavage fluid of pigs infected with HP-PRRSV, and the supernatant of HP-PRRSV infected pulmonary alveolar macrophages were respectively collected to treat the pulmonary microvascular endothelial cells (PMVECs) in Transwell culture system to explore the mechanism of pulmonary microvascular endothelial barrier leakage caused by viral infection. Cytokine screening, addition and blocking experiments revealed that proinflammatory cytokines IL-1ß and TNF-α, secreted by HP-PRRSV-infected macrophages, disrupt the pulmonary microvascular endothelial barrier by downregulating claudin-8 and upregulating claudin-4 synergistically. Additionally, three transcription factors interleukin enhancer binding factor 2 (ILF2), general transcription factor III C subunit 2 (GTF3C2), and thyroid hormone receptor-associated protein 3 (THRAP3), were identified to accumulate in the nucleus of PMVECs, regulating the transcription of claudin-8 and claudin-4. Meanwhile, the upregulation of ssc-miR-185 was found to suppress claudin-8 expression via post-transcriptional inhibition. This study not only reveals the molecular mechanisms by which HP-PRRSV infection causes endothelial barrier leakage in acute lung injury, but also provides novel insights into the function and regulation of tight junctions in vascular homeostasis.

Synthesis of MPEG-b-PLLA Diblock Copolymers and Their Crystallization Performance with PDLA and PLLA Composite Films.

Methoxy poly(ethylene glycol)-block-poly(L-lactide) (MPEG-b-PLLA) has a wide range of applications in pharmaceuticals and biology, and its structure and morphology have been thoroughly studied. In the experiment, we synthesized MPEG-b-PLLA with different block lengths using the principle of ring-opening polymerization by controlling the amount of lactic acid added. The thermodynamic properties of copolymers and the crystallization properties of blends were studied separately. The crystallization kinetics of PDLA/MPEG-b-PLA and PLLA/MPEG-b-PLA composite films were studied using differential scanning calorimetry (DSC). The results indicate that the crystallization kinetics of composite films are closely related to the amount of block addition. The crystallinity of the sample first increases and then decreases with an increase in MPEG-b-PLLA content. These results were also confirmed in polarized optical microscope (POM) and wide-angle X-ray diffraction (WAXD) tests. When 3% MPEG-b-PLLA was added to the PDLA matrix, the blend exhibited the strongest crystallization performance.

Illness perception profile among cancer patients and its influencing factors: A cross-sectional study.

PURPOSE: The purpose of this study was to explore latent profiles of illness perception among cancer patients and its influencing factors. METHODS: This study was a cross-sectional study adopting convenience sampling to select cancer patients from two hospitals in China. A total of 286 patients completed Brief Illness Perception Questionnaire, Post-traumatic Growth Inventory, Fear of Disease Progression Questionnaire and Psychosocial Adjustment to Illness Scale. Latent profile analysis and multiple linear regression were performed to explore the subgroups and factors influencing classification. RESULTS: Three subgroups were identified, which were labelled as "Moderate Illness Perception Group" (16.8%; C1), "High Illness Perception with Heightened Concerns Group" (68.5%; C2) and "High Resilience and Low Symptomatic Impact Group" (14.7%; C3). Specifically, "Normal", "Mild symptom" and "Bed time during the day <50%" of "Functional Status" were more associated with C3. "Worker", "Farmer" and "Self-employed" were more associated with C1 and C2. Patients who had more "knowledge of the disease" were more associated with C2 and C3, who had less "post-traumatic growth" were more associated with C1, and who had less "fear of disease progression" and more "psychosocial adjustment" were more associated with C3 (all P < 0.05). CONCLUSIONS: There was significant variability of illness perception among three subgroups of cancer patients, which emphasized the complexity of psychological condition. The insights derived from these distinct profiles enables tailored interventions and patient-centered communication strategies. However, integrating objective measures or biomarkers is needed to complement self-reported data.

Ferroelectric Resistance Switching in Epitaxial BiFeO3/La0.7Sr0.3MnO3 Heterostructures.

BiFeO3/La0.7Sr0.3MnO3 (BFO/LSMO) epitaxial heterostructures were successfully synthesized by pulsed laser deposition on (001)-oriented SrTiO3 single-crystal substrates with Au top electrodes. Stable bipolar resistive switching characteristics regulated by ferroelectric polarization reversal was observed in the Au/BFO/LSMO heterostructures. The conduction mechanism was revealed to follow the Schottky emission model, and the Schottky barriers in high-resistance and low-resistance states were estimated based on temperature-dependent current-voltage curves. Further, the observed memristive behavior was interpreted via the modulation effect on the depletion region width and the Schottky barrier height caused by ferroelectric polarization reversal, combining with the oxygen vacancies migration near the BFO/LSMO interface.

Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells.

The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by the boundaries of topologically associating domains (TADs), demonstrating the role of the 3D genome structure in modulating the spatial distribution of RNA. Conversely, stopping transcription or acute depletion of RNA induces thousands of chromatin loops genome-wide. Activation or suppression of the transcription of specific genes suppresses or creates chromatin loops straddling these genes. Deletion of a specific caRNA-producing genomic sequence promotes chromatin loops that straddle the interchromosomal target sequences of this caRNA. These data suggest a feedback loop where the 3D genome modulates the spatial distribution of RNA, which in turn affects the dynamic 3D genome organization.

A novel strategy to attenuate porcine reproductive and respiratory syndrome virus by inhibiting viral replication in the target pulmonary alveolar macrophages via hematopoietic-specific miR-142.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen for the global pork industry. Although modified live virus (MLV) vaccines are commonly used for PRRSV prevention and control,  they still carry a risk of infecting the host and replicating in target cells, thereby increasing the likehood of virus recombination and reversion to virulence. In this study, we inserted the target sequence of miR-142 into the nsp2 hypervariable region of PRRSV to inhibit viral replication in its host cells of pigs, with the aim of achieving virus attenuation. The chimeric virus RvJX-miR-142t was successfully rescued and retained its growth characteristics in MARC-145 cells. Furthermore, it did not replicate in MARC-145 cells transfected with miRNA-142 mimic. We also observed limited replication ability of RvJX-miR-142t in pulmonary alveolar macrophages, which are the main cell types that PRRSV infects. Our animal inoculation study showed that pigs infected with RvJX-miR-142t displayed less severe clinical symptoms, lower viremia titers, lighter lung lesions, and significantly lower mortality rates during the first 7 days post-inoculation, in comparison to pigs infected with the backbone virus RvJXwn. We detected a partially deletion of the miR-142 target sequence in the RvJX-miR-142t genome at 14 dpi. It is highly possible that the reversion of viral virulence observed in the later timepoints of our animal experiment was caused by that. Our study provided a new strategy for attenuating PRRSV and confirmed its effectiveness. However, further studies are necessary to increase the stability of this virus under host selection pressure.

Recent advances in enhancing stereocomplexation between poly(lactide) enantiomeric chains.

Over the past three decades, its excellent biodegradability and biocompatibility have enabled poly(lactide) (PLA) to be extensively explored as a replacement for oil-based thermoplastics in biomedical and industrial applications. However, PLA homopolymers have "facilitative" limitations such as low mechanical properties, low processing temperatures, slow recrystallization, and insufficient crystallinity, which have usually hindered commercial PLA in industrial and biomedical applications. The formation of stereo-complexation between enantiomeric poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) chains offers an effective approach to PLA-based engineering materials with improved properties. In this review, we have understandably summarized recent progress in improving the SC crystallization of PLA-based plastics into two aspects, i.e., enantiomeric PLA homopolymers, and enantiomeric PLA-based copolymers. One important point to be noted is that much emphasis is focused on improving SC crystallization by enhancing interactions in the enantiomeric PLA-based copolymers. There is an insightful discussion about the effect of enhanced SC crystallization as well as intermolecular interactions between PLLA and PDLA chains in various stereocomplexable systems. Most importantly, this review starts with the basic understanding of SC crystallization and further elaborates on the rational mechanism of enhanced SC crystallization to provide a broad idea for broadening the road toward PLA-based materials.

The characteristics and clinical relevance of tumor fusion burden in non-EBV (+) gastric cancer with MSS.

BACKGROUND: Next-generation sequencing (NGS) is maturely applied for gene fusion detection. Although tumor fusion burden (TFB) has been identified as an immune marker for cancer, the relationship between these fusions and the immunogenicity and molecular characteristics of gastric cancer (GC) patients remains unclear. GCs have different clinical significance depending on their subtypes, and thus, this study aimed to investigate the characteristics and clinical relevance of TFB in non-Epstein-Barr-virus-positive (EBV+) GC with microsatellite stability (MSS). METHODS: A total of 319 GC patients from The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and a cohort of 45-case from ENA (PRJEB25780) were included. The cohort characteristics and distribution of TFB among the patients were analyzed. Additionally, the correlations of TFB with mutation characteristics, pathway differences, relative abundance of immune cells, and prognosis were examined in the TCGA-STAD cohort of MSS and non-EBV (+) patients. RESULTS: We observed that in the MSS and non-EBV (+) cohort, the TFB-low group exhibited significantly lower gene mutation frequency, gene copy number, loss of heterozygosity score, and tumor mutation burden than in the TFB-high group. Additionally, the TFB-low group exhibited a higher abundance of immune cells. Furthermore, the immune gene signatures were significantly upregulated in the TFB-low group, 2-year disease-specific survival was markedly increased in the TFB-low group compared with to the TFB-high group. The rates of TFB-low cases were significantly higher TFB-than high cases in durable clinical benefit (DCB) and response groups with pembrolizumab treatment. Low TFB may serve as a predictor of GC prognosis, and the TFB-low group exhibits higher immunogenicity. CONCLUSION: In conclusion, this study reveals that the TFB-based classification of GC patient may be instructive for individualized immunotherapy regimens.

Evaluating anti-viral effect of Tylvalosin tartrate on porcine reproductive and respiratory syndrome virus and analyzing the related gene regulation by transcriptomics.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen, characterized by its genetic and antigenic variation. The PRRSV vaccine is widely used, however, the unsatisfied heterologic protection and the risk of reverse virulence raise the requirement to find some new anti-PRRSV strategies for disease control. Tylvalosin tartrate is used to inhibit PRRSV in the field non-specifically, however, the mechanism is still less known. METHODS: The antiviral effects of Tylvalosin tartrates from three producers were evaluated in a cell inoculation model. Their safety and efficacy concentrations, and effecting stage during PRRSV infection were analyzed. And, the Tylvalosin tartrates regulated genes and pathways which are potentially related to the anti-viral effect were further explored by using transcriptomics analysis. Last, the transcription level of six anti-virus-related DEGs was selected to confirm by qPCR, and the expression level of HMOX1, a reported anti-PRRSV gene, was proved by western blot. RESULTS: The safety concentrations of Tylvalosin tartrates from three different producers were 40 µg/mL (Tyl A, Tyl B, and Tyl C) in MARC-145 cells and 20 µg/mL (Tyl A) or 40 µg/mL (Tyl B and Tyl C) in primary pulmonary alveolar macrophages (PAMs) respectively. Tylvalosin tartrate can inhibit PRRSV proliferation in a dose-dependent manner, causing more than 90% proliferation reduction at 40 µg/mL. But it shows no virucidal effect, and only achieves the antiviral effect via long-term action on the cells during the PRRSV proliferation. Furthermore, GO terms and KEGG pathway analysis was carried out based on the RNA sequencing and transcriptomic data. It was found that the Tylvalosin tartrates can regulate the signal transduction, proteolysis, and oxidation-reduction process, as well as some pathways such as protein digestion and absorption, PI3K-Akt signaling, FoxO signaling, and Ferroptosis pathways, which might relate to PRRSV proliferation or host innate immune response, but further studies still need to confirm it. Among them, six antivirus-related genes HMOX1, ATF3, FTH1, FTL, NR4A1, and CDKN1A were identified to be regulated by Tylvalosin tartrate, and the increased expression level of HMOX1 was further confirmed by western blot. CONCLUSIONS: Tylvalosin tartrate can inhibit PRRSV proliferation in vitro in a dose-dependent manner. The identified DEGs and pathways in transcriptomic data will provide valuable clues for further exploring the host cell restriction factors or anti-PRRSV target.

Robustness of calibration model for prediction of lignin content in different batches of snow pears based on NIR spectroscopy.

Snow pear is very popular in southwest China thanks to its fruit texture and potential medicinal value. Lignin content (LC) plays a direct and negative role (higher concentration and larger size of stone cells lead to thicker pulp and deterioration of the taste) in determining the fruit texture of snow pears as well as consumer purchasing decisions of fresh pears. In this study, we assessed the robustness of a calibration model for predicting LC in different batches of snow pears using a portable near-infrared (NIR) spectrometer, with the range of 1033-2300 nm. The average NIR spectra at nine different measurement positions of snow pear samples purchased at four different periods (batch A, B, C and D) were collected. We developed a standard normal variate transformation (SNV)-genetic algorithm (GA) -the partial least square regression (PLSR) model (master model A) - to predict LC in batch A of snow pear samples based on 80 selected effective wavelengths, with a higher correlation coefficient of prediction set (Rp) of 0.854 and a lower root mean square error of prediction set (RMSEP) of 0.624, which we used as the prediction model to detect LC in three other batches of snow pear samples. The performance of detecting the LC of batch B, C, and D samples by the master model A directly was poor, with lower Rp and higher RMSEP. The independent semi-supervision free parameter model enhancement (SS-FPME) method and the sequential SS-FPME method were used and compared to update master model A to predict the LC of snow pears. For the batch B samples, the predictive ability of the updated model (Ind-model AB) was improved, with an Rp of 0.837 and an RMSEP of 0.614. For the batch C samples, the performance of the Seq-model ABC was improved greatly, with an Rp of 0.952 and an RMSEP of 0.383. For the batch D samples, the performance of the Seq-model ABCD was also improved, with an Rp of 0.831 and an RMSEP of 0.309. Therefore, the updated model based on supervision and learning of new batch samples by the sequential SS-FPME method could improve the robustness and migration ability of the model used to detect the LC of snow pears and provide technical support for the development and practical application of portable detection device.

The Oral PI3Kδ Inhibitor Linperlisib for the Treatment of Relapsed and/or Refractory Follicular Lymphoma: A Phase II, Single-Arm, Open-Label Clinical Trial.

PURPOSE: To investigate the efficacy and safety of the novel orally active PI3Kδ inhibitor in relapsed and/or refractory patients with follicular lymphoma (FL) who had received at least two prior systemic treatments. PATIENTS AND METHODS: Histologically confirmed relapsed and/or refractory patients with FL with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate, and drug safety profile. RESULTS: Of 114 screened relapsed and/or refractory patients with FL, 84 were enrolled in the full analysis set (FAS). The ORR of the 84 FAS patients was 79.8% [95% confidence interval (CI), 69.6-87.8, 67 patients], with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (95% CI, 9.3-15.9). The median PFS was 13.4 months (95% CI, 11.1-16.7). The 12-month OS rate was 91.4% (95% CI, 82.7-95.8) and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events Grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%), and interstitial lung disease (3.6%). CONCLUSIONS: Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory patients with FL who had received at least two prior systemic therapies.

Sphingosine 1-phosphate receptor 2 promotes the onset and progression of non-alcoholic fatty liver disease-related hepatocellular carcinoma through the PI3K/AKT/mTOR pathway.

PURPOSE: Recent studies have revealed an increase in the incidence rate of non-alcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC). Furthermore, the association of Sphingosine 1-phosphate receptor 2 (S1PR2) with various types of tumours is identified, and the metabolism of conjugated bile acids (CBAs) performs an essential function in the onset and development of HCC. However, the association of CBA and S1PR2 with NAFLD-HCC is unclear. METHODS: The relationship between the expression of S1PR2 and the prognosis of patients suffering from NAFLD-HCC was investigated by bioinformatics techniques. Subsequently, the relationship between S1PR2 and the biological behaviours of HCC cell lines Huh 7 and HepG2 was explored by conducting molecular biology assays. Additionally, several in vivo animal experiments were carried out for the elucidation of the biological impacts of S1PR2 inhibitors on HCC cells. Finally, We used Glycodeoxycholic acid (GCDA) of CBA to explore the biological effects of CBA on HCC cell and its potential mechanism. RESULTS: High S1PR2 expression was linked to poor prognosis of the NAFLD-HCC patients. According to cellular assay results, S1PR2 expression could affect the proliferation, invasion, migration, and apoptosis of Huh 7 and HepG2 cells, and was closely associated with the G1/G2 phase of the cell cycle. The experiments conducted in the In vivo conditions revealed that the overexpression of S1PR2 accelerated the growth of subcutaneous tumours. In addition, JTE-013, an antagonist of S1PR2, effectively inhibited the migration and proliferation of HCC cells. Furthermore, the bioinformatics analysis highlighted a correlation between S1PR2 and the PI3K/AKT/mTOR pathway. GCDA administration further enhanced the expression levels of p-AKT, p-mTOR, VEGF, SGK1, and PKCα. Moreover, both the presence and absence of GCDA did not reveal any significant change in the levels of S1PR2, p-AKT, p-mTOR, VEGF, SGK1, and PKCα proteins under S1PR2 knockdown, indicating that CBA may regulates the PI3K/AKT/mTOR pathway by mediating S1PR2 expression. CONCLUSION: S1PR2 is a potential prognostic biomarker in NAFLD-HCC. In addition, We used GCDA in CBAs to treat HCC cell and found that the expression of S1PR2 was significantly increased, and the expression of PI3K/AKT/mTOR signalling pathway-related signal molecules was also significantly enhanced, indicating that GCDA may activate PI3K/AKT/mTOR signalling pathway by up-regulating the expression of S1PR2, and finally affect the activity of hepatocellular carcinoma cells. S1PR2 can be a candidate therapeutic target for NAFLD-HCC. Collectively, the findings of this research offer novel perspectives on the prevention and treatment of NAFLD-HCC.

Role of the Branched PEG-b-PLLA Block Chain in Stereocomplex Crystallization and Crystallization Kinetics for PDLA/MPEG-b-PLLA-g-glucose Blends with Different Architectures.

The isothermal crystallization behavior and corresponding morphology evolution of poly(d-lactic acid) (PDLA) blends with PLLA6.7k or MPEG-b-PLLA6.7k-g-glucose with different architectures and different PLLA-grafted copolymer contents were investigated. The formation of stereocomplexes (SCs) in between the chain branched structure of MPEG-b-PLLA6.7k-g-glucose and PDLA chains acting as the physical crosslinking points slows down the motion of PDLA chains, but the SCs could act as a heterogeneous nucleating agent for the late formation of homocrystals (HCs) in the blend system, accelerating the crystallization kinetics of HCs through enhancing the nucleation density. For PDLA/MPEG-b-PLLA6.7k-g-glucose blends, the mobility of SCs in the blend system and the nucleation density of SCs in the blends exhibit oppositional behavior during the isothermal crystallization at a Tc of 130 °C. The evolution of the crystal growth and structure during the isothermal crystallization process by rheometry has revealed the interesting role of the branched chains of MPEG-b-PLLA6.7k-g-glucose in the mechanism of the crystallization in PDLA blends.

Self-Adhesive and Conductive Dual-Network Polyacrylamide Hydrogels Reinforced by Aminated Lignin, Dopamine, and Biomass Carbon Aerogel for Ultrasensitive Pressure Sensor.

Conductive hydrogels have attracted extensive interest owing to its potential in soft robotics, electronic skin, and human monitoring. However, insufficient mechanical properties, lower adhesivity, and unsatisfactory conductivity seriously hinder potential applications in this emerging field. Herein, a highly elastic conductive hydrogel with a combination of favorable mechanical properties, self-adhesiveness, and excellent electrical performance was achieved by the synergistic effect of aminated lignin (AL), polydopamine (PDA), polyacrylamide (PAM) chains, and biomass carbon aerogel (C-SPF). In detail, AL was applied to induce slow oxidative polymerization of DA for preparing the sticky hydrogel containing PDA. Then, C-SPF carbon aerogel was used as a matrix to construct a dual-network structured composite hydrogel by combining with the hydrogels derived from PDA, AL, and PAM. The as-prepared conductive hydrogel displayed excellent mechanical performance, strong adhesive strength, and repeatable adhesivity. The prepared hydrogel-based pressure sensor possessed fast response (0.6 s loading and 0.8 s unloading stress time), high response (maximum RCR = 1.8 × 104), wide working pressure range (from 0 to 240.0 kPa), and excellent durability (stable 500 compression cycles with 30% deformation). In addition, the prepared sensor also displayed ultrahigh sensitivity (170 kPa-1), which was near 4 orders of magnitude higher than the conventional lignin-modified PAM hydrogels. The multiple interactions between hydrogel components and the mechanical properties of hydrogel were also verified by molecular dynamics investigation. Moreover, the excellent cytocompatibility and antibacterial activity of this composite hydrogel ensured high potential in various applications such as human/machine interaction, artificial intelligence, personal healthcare, and wearable devices.

Competitive Mechanism of Stereocomplexes and Homocrystals in High-Performance Symmetric and Asymmetric Poly(lactic acid) Enantiomers: Qualitative Methods.

To systematically explore the critical contributions of both molecular weights and crystallization temperature and chain length and molar ratios to the formation of stereocomplexes (SCs), our group quantitatively prepared a wide MW range of symmetric and asymmetric poly(lactic acid) (PLA) racemic blends, which contains L-MW PLLA with M n > 6k g/mol. The crystallinity and relative fraction of SCs increase with T c, and the SCs are exclusively formed at T c > 180 °C in M/H-MW racemic blends. When MWs of one of the enantiomers are over 6k and less than 41k, multiple stereocomplexation is clear in the asymmetric racemic blends and more ordered SCs form with less entanglement or the amorphous region compared to those for the MW of the enantiomers over 41k in the symmetric/asymmetric enantiomers. When the MW of the blends is more than 41k, SCs and homocrystals (HCs) coexist in the symmetric enantiomers and the multicomplexation can restrict the asymmetric enantiomers. This study provides a deep comprehensive insight into the stereocomplex crystallization mechanism of polymers and provides a reference value for future research attempting to prepare stereocomplex materials.

Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells.

The porcine reproductive and respiratory syndrome virus (PRRSV), especially the highly pathogenic strains, can cause serious acute lung injury (ALI), characterized by extensive hemorrhage, inflammatory cells and serous fluid infiltration in the lung vascular system. Meanwhile, the pulmonary microvascular endothelial cells (PMVECs) are essential for forming the air-blood barrier and keeping the water-salt balance to prevent leakage of circulating nutrients, solutes, and fluid into the underlying tissues. As well, they tightly regulate the influx of immune cells. To determine the possible relationship between the PMVECs' function changes and lung vascular permeability during PRRSV infection, the PMVECs were co-cultured with HP-PRRSV-inoculated primary pulmonary alveolar macrophages (PAMs) in transwell model, and then the RNA sequencing (RNA-seq) and comprehensive bioinformatics analysis were carried out to characterize the dynamic transcriptome landscapes of PMVECs. In total, 16,489 annotated genes were identified, with 275 upregulated and 270 downregulated differentially expressed genes (DEGs) were characterized at both 18 and 24 h post PRRSV inoculation. The GO terms and KEGG pathways analysis indicated that the immune response, metabolic pathways, cell death, cytokine-cytokine receptor interaction, viral responses, and apoptotic process are significantly regulated upon co-culture with PRRSV-infected PAMs. Moreover, according to the TERR and dextran flux assay results, dysregulation of TJ proteins, including CLDN1, CLDN4, CLDN8, and OCLN, is further confirmed to correlate with the increased permeability of PMVECs. These transcriptome profiles and DEGs will provide valuable clues for further exploring the roles of PMVECs in PRRSV-induced ALI in the future.

Evolutionary Patterns of Codon Usage in Major Lineages of Porcine Reproductive and Respiratory Syndrome Virus in China.

Porcine reproductive and respiratory syndrome virus (PRRSV) is economically important and characterized by its extensive variation. The codon usage patterns and their influence on viral evolution and host adaptation among different PRRSV strains remain largely unknown. Here, the codon usage of ORF5 genes from lineages 1, 3, 5, and 8, and MLV strains of type 2 PRRSV in China was analyzed. A compositional property analysis of ORF5 genes revealed that nucleotide C is most frequently used at the third position of codons, accompanied by rich GC3s. The effective number of codon (ENC) and codon pair bias (CPB) values indicate that all ORF5 genes have low codon bias and the differences in CPB scores among four lineages are almost not significant. When compared with host codon usage patterns, lineage 1 strains show higher CAI and SiD values, with a high similarity to pig, which might relate to its predominant epidemic propensity in the field. The CAI, RCDI, and SiD values of ORF5 genes from different passages of MLV JXA1R indicate no relation between attenuation and CPB or codon adaptation decrease during serial passage on non-host cells. These findings provide a novel way of understanding the PRRSV's evolution, related to viral survival, host adaptation, and virulence.

Low crystalline 1T-MoS2@S-doped carbon hollow spheres as an anode material for Lithium-ion battery.

A low crystalline 1T-MoS2@S-doped carbon (MoS2@SC) composite was successfully synthesized via a facile hydrothermal process. The composite is comprised by few-layer 1T-MoS2 nanosheets covered by an amorphous carbon layer with an expanded interlayer d-spacing of 1.01 nm. This structure is conducive to the fast transport of lithium-ions and volume accommodation during the charge-discharge process when the composite is applied as an anode material for LIBs. Additionally, the high conductivity and layered structure of 1T-MoS2 also facilitate fast of ion/electron transport, contributing to the improvement of the electrochemical properties. Therefore, this material demonstrated a high rate performance and excellent cycling stability, with the capacities of 847 and 622 mA h g-1 achieved at the current densities of 0.2 A g-1 and 2 A g-1, respectively. Even at a larger current density of 2 A g-1, MoS2@SC delivered a high reversible capacity of 659 mA h g-1 with an average capacity loss of 0.006% per cycle after 500 cycles.

The periodic traveling waves in a diffusive periodic SIR epidemic model with nonlinear incidence.

In this paper, a reaction-diffusion SIR epidemic model is proposed. It takes into account the individuals mobility, the time periodicity of the infection rate and recovery rate, and the general nonlinear incidence function, which contains a number of classical incidence functions. In our model, due to the introduction of the general nonlinear incidence function, the boundedness of the infected individuals can not be obtained, so we study the existence and nonexistence of periodic traveling wave solutions of original system with the aid of auxiliary system. The basic reproduction number R 0 and the critical wave speed c * are given. We obtained the existence and uniqueness of periodic traveling waves for each wave speed c > c * using the Schauder's fixed points theorem when R 0 > 1 . The nonexistence of periodic traveling waves for two cases (i) R 0 > 1 and 0 < c < c * , (ii) R 0 ≤ 1 and c ≥ 0 are also obtained. These results generalize and improve the existing conclusions. Finally, the numerical experiments support the theoretical results. The differences of traveling wave solution between periodic system and general aperiodic coefficient system are analyzed by numerical simulations.

Nanocomposite of ultra-small MoO2 embedded in nitrogen-doped carbon: In situ derivation from an organic molybdenum complex and its superior Li-Ion storage performance.

MoO2 is a promising anode material for lithium-ion batteries, however, the lithiation of bulk MoO2 is usually limited to addition-type reaction at room temperature, and the conversion reaction is hindered because of the sluggish kinetics. Herein, a nanocomposite of MoO2 embedded in nitrogen-doped carbon (MoO2/NC) is synthesized through the in situ thermolysis of an organic molybdenum complex MoO2(acac)(phen) (acac = acetylacetone, phen = 1,10-Phenanthroline). Owing to the fact that [MoO2]2+ can be strongly chelated by phen, the molybdenum source in the MoO2(acac)(phen) precursor is highly dispersed, leading to the formation of ultra-small MoO2 nanoparticles in the nanocomposite, which can facilitate the conversion reaction. Moreover, the NC matrix can guarantee a high electrical conductivity and effectively accommodate the volume changes triggered by the conversion reaction. Consequently, the MoO2/NC nanocomposite exhibits outstanding electrochemical properties, including large reversible capacity of 950 mA h g-1 at 0.1 A g-1, high-rate capability of 605 mA h g-1 at 2 A g-1, and excellent cycling stability over 500 cycles as an anode material for lithium-ion batteries.