Advances in the immunoescape mechanisms exploited by alphaherpesviruses.

Alphaherpesviruses, categorized as viruses with linear DNA composed of two complementary strands, can potentially to induce diseases in both humans and animals as pathogens. Mature viral particles comprise of a core, capsid, tegument, and envelope. While herpesvirus infection can elicit robust immune and inflammatory reactions in the host, its persistence stems from its prolonged interaction with the host, fostering a diverse array of immunoescape mechanisms. In recent years, significant advancements have been achieved in comprehending the immunoescape tactics employed by alphaherpesviruses, including pseudorabies virus (PRV), herpes simplex virus (HSV), varicella-zoster virus (VZV), feline herpesvirus (FeHV), equine herpesvirus (EHV), and caprine herpesvirus type I (CpHV-1). Researchers have unveiled the intricate adaptive mechanisms existing between viruses and their natural hosts. This review endeavors to illuminate the research advancements concerning the immunoescape mechanisms of alphaherpesviruses by delineating the pertinent proteins and genes involved in virus immunity. It aims to furnish valuable insights for further research on related mechanisms and vaccine development, ultimately contributing to virus control and containment efforts.

Consistent Thermal Conductivities of Spring-Like Structured Polydimethylsiloxane Composites under Large Deformation.

Flexible and highly thermally conductive materials with consistent thermal conductivity (λ) during large deformation are urgently required to address the heat accumulation in flexible electronics. In this study, spring-like thermal conduction pathways of silver nanowire (S-AgNW) fabricated by 3D printing are compounded with polydimethylsiloxane (PDMS) to prepare S-AgNW/PDMS composites with excellent and consistent λ during deformation. The S-AgNW/PDMS composites exhibit a λ of 7.63 W m-1 K-1 at an AgNW amount of 20 vol%, which is ≈42 times that of PDMS (0.18 W m-1 K-1) and higher than that of AgNW/PDMS composites with the same amount and random dispersion of AgNW (R-AgNW/PDMS) (5.37 W m-1 K-1). Variations in the λ of 20 vol% S-AgNW/PDMS composites are less than 2% under a deformation of 200% elongation, 50% compression, or 180° bending, which benefits from the large deformation characteristics of S-AgNW. The heat-transfer coefficient (0.29 W cm-2 K-1) of 20 vol% S-AgNW/PDMS composites is ≈1.3 times that of the 20 vol% R-AgNW/PDMS composites, which reduces the temperature of a full-stressed central processing unit by 6.8 °C compared to that using the 20 vol% R-AgNW/PDMS composites as a thermally conductive material in the central processing unit.

How to apply ex-vivo split liver transplantation safely and feasibly: A three-step approach.

BACKGROUND: Given the current organ shortage crisis, split liver transplantation (SLT) has emerged as a promising alternative for select end-stage liver disease patients. AIM: To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT. METHODS: A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1, 2022, and May 31, 2023. The study included 25 SLT cases and 81 whole liver transplantation (WLT) cases. Total ex-vivo liver splitting was employed for SLT graft procurement in three steps. Patient outcomes were determined, including liver function parameters, postoperative complications, and perioperative mortality. Group comparisons for categorical variables were performed using the χ²-test. RESULTS: In the study, postoperative complications in the 25 SLT cases included hepatic artery thrombosis (n = 1) and pulmonary infections (n = 3), with no perioperative mortality. In contrast, among the 81 patients who underwent WLT, complications included perioperative mortality (n = 1), postoperative pulmonary infections (n = 8), abdominal infection (n = 1), hepatic artery thromboses (n = 3), portal vein thrombosis (n = 1), and intra-abdominal bleeding (n = 5). Comparative analysis demonstrated significant differences in alanine aminotransferase (176.0 vs 73.5, P = 0.000) and aspartate aminotransferase (AST) (42.0 vs 29.0, P = 0.004) at 1 wk postoperatively, and in total bilirubin (11.8 vs 20.8, P = 0.003) and AST (41.5 vs 26.0, P = 0.014) at 2 wk postoperatively. However, the overall incidence of complications was comparable between the two groups (P > 0.05). CONCLUSION: Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach, especially under the expertise of an experienced transplant center. The approach developed by our center can serve as a valuable reference for other transplantation centers.

Prospective cohort studies underscore the association of abnormal glycemic measures with all-cause and cause-specific mortalities.

The role of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and triglyceride-glucose index (TyG index) in predicting all-cause and cause-specific mortalities remains elusive. This study included 384,420 adults from the Shanghai cohort and the UK Biobank (UKB) cohort. After multivariable adjustment in the Cox models, FPG ≥7.0 mmol/L or HbA1c ≥ 6.5% increased the risk of all-cause mortality, FPG ≥5.6 mmol/L or HbA1c ≥ 6.5% increased CVD-related mortality, and higher or lower TyG index increased all-cause and CVD-related mortalities in the Shanghai cohort; FPG ≥5.6 mmol/L, HbA1c ≥ 5.7%, TyG index <8.31 or ≥9.08 increased the risks of all-cause, CVD-related, and cancer-related mortalities in the UKB cohort. FPG or HbA1c increased the discrimination of the conventional risk model in predicting all-cause and CVD-related mortalities in both cohorts. Thus, increased levels of FPG and HbA1c and U-shaped TyG index increase the risks of all-cause especially CVD-related mortalities.

Sophora subprostrate polysaccharide targets LncRNA MSTRG.5823.1 to suppress PCV2-mediated immunosuppression via TNF/NF-κB signaling.

Current evidence suggests that porcine circovirus type 2 (PCV2) infection induces immunosuppression in piglets. Sophora subprostrate polysaccharide (SSP) exhibits various pharmacological activities, including immunoregulatory, anti-inflammatory, antiviral, and antioxidant properties. However, the acts of lncRNAs in regulating the therapeutic effects of SSP on PCV2-infected RAW264.7 cells remains poorly understood. This study aimed to investigate the molecular mechanisms by which lncRNAs regulate PCV2-induced immunosuppression during SSP treatment. Our findings revealed that 1699 mRNAs, 373 lncRNAs, and 129 miRNAs were differentially expressed in PCV2-infected RAW264.7 cells. Additionally, 359 mRNAs, 271 lncRNAs, and 79 miRNAs exhibited differential expression in SSP-treated PCV2-infected RAW264.7 cells. GO and KEGG analyses indicated that the candidate genes were enriched in the TNF/NF-κB signaling pathway. Furthermore, based on GO and KEGG pathway analysis, a ceRNA network involving chemokine (C-X-C motif) ligand 2 (CXCL2), miR-217-x, and MSTRG.5823.1 was constructed. We demonstrated that lncRNA MSTRG.5823.1 localized to the cytoplasm. Moreover, we found that silencing or overexpressing lncRNA MSTRG.5823.1 significantly modulated PCV2-induced immunosuppression by regulating the activation of the TNF/NF-κB signaling pathway. Specifically, lncRNA MSTRG.5823.1 overexpression increased the expression of TNF/NF-κB signaling pathway-related genes and proteins in PCV2-infected RAW264.7 cells. Conversely, silencing lncRNA MSTRG.5823.1 decreased their expression. Rescue assays further revealed that the suppressive effects of miR-217-x overexpression on TNF/NF-κB signaling pathway-related genes and proteins could be reversed by MSTRG.5823.1 overexpression. These findings highlight the critical role of lncRNA MSTRG.5823.1 in PCV2 infection progression and suggest a new strategy for the prevention and treatment of PCV2 infection.

[Plankton Community Stability and Drive Factor Identification Guizhou Plateau Reservoir].

In order to understand the stability of the zooplankton and phytoplankton communities in the Guizhou plateau reservoir environment, the process of reservoir water quality change affecting the stability of plankton was studied. The changes in the plankton community and water quality in three different nutrient reservoirs （Huaxi Reservoir, Goupitan Reservoir, and Hailong Reservoir） were studied from October 2020 to August 2021. The stability of the zooplankton and phytoplankton communities was studied using time-lag analysis （TLA）. Variance decomposition analysis （VPA） was used to explore the response of the two communities to environmental changes. The driving factors of plankton community changes in reservoirs were also revealed. The results showed that Huaxi Reservoir and Goupitan Reservoir were mesotrophic reservoirs, and Hailong Reservoir was a eutrophic reservoir. The average comprehensive nutrition indices of the three reservoirs were 44.07, 44.68, and 50.25. A total of 51 species of zooplankton rotifers, 39 species of rotifers, three species of copepods, and nine species of cladocera were identified. Among them, the abundance of rotifers was the highest, accounting for 85.96%. A total of seven phyla and 73 species of phytoplankton were identified, including 16 species in the phylum Cyanophyta, 32 species in the phylum Chlorophyta, 16 species in the phylum Diatoma, three species in the phylum Chlorophyta, four species in the phylum Euglenophyta, and one species each in the phyla Cryptophyta and Chrysophyta. Among them, the abundance of cyanobacteria and diatoms was the highest, accounting for 66.2% and 27.35%, respectively. The median absolute deviation （MAD） of the Bray-Curtis distance of zooplankton and phytoplankton community in the three reservoirs were 0.67 and 0.65 in Huaxi Reservoir, 0.80 and 0.69 in Goupitan Reservoir, and 0.85 and 0.47 in Hailong Reservoir, respectively. The larger the value, the greater the variation in the community. The absolute value of the slope of zooplankton was greater than that of phytoplankton in the TLA results, and the absolute values of the slopes were 0.018 and 0.004, respectively. The larger the absolute value of the slope, the faster the community variability. The zooplankton community in the three reservoirs was less stable than the phytoplankton community and more sensitive to environmental changes, and the degree of variation was greater. The higher the degree of eutrophication of the reservoir, the more obvious this phenomenon. VPA showed that the changes in plankton communities in Huaxi Reservoir and Hailong Reservoir were mainly influenced by water temperature and eutrophication factors. The changes in planktonic community in Goupitan Reservoir were mainly influenced by water temperature and chemical factors. The driving factors of Huaxi Reservoir were water temperature, TP, permanganate index, and SD. The driving factors of Goupitan Reservoir were water temperature, NO3-- N, and pH. The driving factors of Hailong Reservoir were water temperature and TP. Nutrients and water temperature were the main factors affecting the stability of plankton communities in reservoirs.

The antibodies against the A137R protein drive antibody-dependent enhancement of African swine fever virus infection in porcine alveolar macrophages.

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a highly contagious disease that can kill up to 100% of domestic pigs and wild boars. It has been shown that the pigs inoculated with some ASF vaccine candidates display more severe clinical signs and die earlier than do pigs not immunized. We hypothesize that antibody-dependent enhancement (ADE) of ASFV infection may be caused by the presence of some unidentified antibodies. In this study, we found that the ASFV-encoded structural protein A137R (pA137R) can be recognized by the anti-ASFV positive sera, indicating that the anti-pA137R antibodies are induced in the ASFV-infected pigs. Interestingly, our results demonstrated that the anti-pA137R antibodies produced in rabbits or pigs enhanced viral replication of different ASFV strains in primary porcine alveolar macrophages (PAMs), the target cells of ASFV. Mechanistic investigations revealed that anti-pA137R antibodies were able to promote the attachment of ASFV to PAMs and two types of Fc gamma receptors (FcγRs), FcγRII and FcγRIII, mediated the ADE of ASFV infection. Taken together, anti-pA137R antibodies are able to drive ASFV ADE in PAMs. These findings shed new light on the roles of anti-ASFV antibodies and have implications for the pathophysiology of the disease and the development of ASF vaccines.

Genetic Variations of African Swine Fever Virus: Major Challenges and Prospects.

African swine fever (ASF) is a contagious viral disease affecting pigs and wild boars. It typically presents as a hemorrhagic fever but can also manifest in various forms, ranging from acute to asymptomatic. ASF has spread extensively globally, significantly impacting the swine industry. The complex and highly variable character of the ASFV genome makes vaccine development and disease surveillance extremely difficult. The overall trend in ASFV evolution is towards decreased virulence and increased transmissibility. Factors such as gene mutation, viral recombination, and the strain-specificity of virulence-associated genes facilitate viral variations. This review deeply discusses the influence of these factors on viral immune evasion, pathogenicity, and the ensuing complexities encountered in vaccine development, disease detection, and surveillance. The ultimate goal of this review is to thoroughly explore the genetic evolution patterns and variation mechanisms of ASFV, providing a theoretical foundation for advancement in vaccine and diagnostic technologies.

The MGF300-2R Protein of African Swine Fever Virus Promotes IKKß Ubiquitination by Recruiting the E3 Ubiquitin Ligase TRIM21.

African swine fever (ASF) is an acute, hemorrhagic, highly contagious disease in pigs caused by African swine fever virus (ASFV). Our previous study identified that the ASFV MGF300-2R protein functions as a virulence factor and found that MGF300-2R degrades IKKß via selective autophagy. However, the E3 ubiquitin ligase responsible for IKKß ubiquitination during autophagic degradation still remains unknown. In order to solve this problem, we first pulled down 328 proteins interacting with MGF300-2R through immunoprecipitation-mass spectrometry. Next, we analyzed and confirmed the interaction between the E3 ubiquitin ligase TRIM21 and MGF300-2R and demonstrated the catalytic role of TRIM21 in IKKß ubiquitination. Finally, we indicated that the degradation of IKKß by MGF300-2R was dependent on TRIM21. In summary, our results indicate TRIM21 is the E3 ubiquitin ligase involved in the degradation of IKKß by MGF300-2R, thereby augmenting our understanding of the functions of MGF300-2R and offering insights into the rational design of live attenuated vaccines and antiviral strategies against ASF.

Ferritin Nanoparticle Delivery of the E2 Protein of Classical Swine Fever Virus Completely Protects Pigs from Lethal Challenge.

Classical swine fever (CSF), caused by the classical swine fever virus (CSFV), results in significant economic losses to the swine industry in many countries. Vaccination represents the primary strategy to control CSF and the CSFV E2 protein is known as the major protective antigen. However, the E2 protein expressed or presented by different systems elicits distinct immune responses. In this study, we established a stable CHO cell line to express the E2 protein and delivered it using self-assembled ferritin nanoparticles (NPs). Subsequently, we compared the adaptive immune responses induced by the E2-ferritin NPs and the monomeric E2 protein produced by the CHO cells or a baculovirus expression system. The results revealed that the NP-delivered E2 protein elicited higher titers of neutralizing antibodies than did the monomeric E2 protein in pigs. Importantly, only the NP-delivered E2 protein significantly induced CSFV-specific IFN-γ-secreting cells. Furthermore, all the pigs inoculated with the E2-ferritin NPs were completely protected from a lethal CSFV challenge infection. These findings demonstrate the ability of the E2-ferritin NPs to protect pigs against the lethal CSFV challenge by eliciting robust humoral and cellular immune responses.

Labdane-type diterpenoids with cytotoxic and anti-inflammatory activities from the aerial parts of Hypoestes purpurea (L.) R. Br.

Two new ent-labdane diterpenoids, hypoestesins A-B (1-2) and five new labdane diterpenoids, hypopurolides H-L (3-7), were isolated from the aerial parts of Hypoestes purpurea. All of the structures were fully determined based on extensive analysis of 1H, 13C, 2D NMR, and HRESIMS data. The absolute configurations of 1-3 was established through comparing the experimental and calculated ECD curves and the structure of 5 was confirmed by single crystal X-ray diffraction experiment. Compounds 5-7 were unusual C23 labdane diterpenoids having a γ-acetonyl-α, ß-unsaturated γ-lactone unit and each assigned as C-15 epimeric mixture. Furthermore, cytotoxic and anti-inflammatory activities of 3-7 were evaluated. The results showed that 3 had remarkable cytotoxic activity against HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 cancer cell lines with IC50 values ranging from 2.35 to 17.06 µM. Compound 4 showed moderate cytotoxic activity against HL-60 and SMMC-7721 cancer cell lines with IC50 values of 15.12 ± 0.53 and 12.92 ± 0.60 µM, respectively. Furthermore, compound 4 was also found to exhibit inhibitory activity against NO production in RAW 264.7 macrophages with IC50 values of 23.56 ± 0.99 µM, compared to the positive control L-NMMA with an IC50 value of 41.11 ± 1.34 µM.

Bubbling resilient 3D free-standing nanoporous graphene with an encapsulated multicomponent nano-alloy for enhanced electrocatalysis.

The design and synthesis of highly durable and active electrocatalysts are crucial for improving the hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs). In this work, we present a novel dealloyed nanoporous PtCuNiCoMn multicomponent alloy with ligaments/pores ranging from 2-3 nm, which is in situ encapsulated in a three-dimensional, free-standing nanoporous nanotubular graphene network featuring a pore/tube diameter of ∼200 to 300 nm. This method allows precise control over the noble metal loading and alloy composition while preventing noble metal loss throughout the preparation process. The innovative bimodal nanoporous graphene/alloy structure, coupled with an open 3D spongy morphology, and optimized surface Pt electronic structure through multicomponent interaction, significantly enhances the activity for the HER/ORR, outperforming commercial Pt/C. Moreover, this design addresses the issues of Pt nanoparticle aggregation and detachment from carbon supports that typically exist in Pt/C-type catalysts, thereby substantially improving the catalytic durability, even under intense gas bubbling conditions.

Estimation of complete mutual information exploiting nonlinear magnitude-phase dependence: Application to spatial FNC for complex-valued fMRI data.

BACKGROUND: Real-valued mutual information (MI) has been used in spatial functional network connectivity (FNC) to measure high-order and nonlinear dependence between spatial maps extracted from magnitude-only functional magnetic resonance imaging (fMRI). However, real-valued MI cannot fully capture the group differences in spatial FNC from complex-valued fMRI data with magnitude and phase dependence. METHODS: We propose a complete complex-valued MI method according to the chain rule of MI. We fully exploit the dependence among magnitudes and phases of two complex-valued signals using second and fourth-order joint entropies, and propose to use a Gaussian copula transformation with a lower bound property to avoid inaccurate estimation of joint probability density function when computing the joint entropies. RESULTS: The proposed method achieves more accurate MI estimates than the two histogram-based (normal and symbolic approaches) and kernel density estimation methods for simulated signals, and enhances group differences in spatial functional network connectivity for experimental complex-valued fMRI data. COMPARISON WITH EXISTING METHODS: Compared with the simplified complex-valued MI and real-valued MI, the proposed method yields higher MI estimation accuracy, leading to 17.4 % and 145.5 % wider MI ranges, and more significant connectivity differences between healthy controls and schizophrenia patients. A unique connection between executive control network (EC) and right frontal parietal areas, and three additional connections mainly related to EC are detected than the simplified complex-valued MI. CONCLUSIONS: With capability in quantifying MI fully and accurately, the proposed complex-valued MI is promising in providing qualified FNC biomarkers for identifying mental disorders such as schizophrenia.

Relations between near-field enhancements and Purcell factors in hybrid nanostructures of plasmonic antennas and dielectric cavities.

Strong near-field enhancements (NFEs) of nanophotonic structures are believed to be closely related to high Purcell factors (FP). Here, we theoretically show that the correlation is partially correct; the extinction cross section (σ) response is also critical in determining FP. The divergence between NFE and FP is especially pronounced in plasmonic-dielectric hybrid systems, where the plasmonic antenna supports dipolar plasmon modes and the dielectric cavity hosts Mie-like resonances. The cavity's enhanced-field environment can boost the antenna's NFEs, but the FP is not increased concurrently due to the larger effective σ that is intrinsic to the FP calculations. Interestingly, the peak FP for the coupled system can be predicted by using the NFE and σ responses. Furthermore, the limits for FP of coupled systems are considered; they are determined by the sum of the FP of a redshifted (or modified, if applicable) antenna and an individual cavity. This contrasts starkly with the behavior of NFE which is closely associated with the multiplicative effects of the NFEs provided by the antenna and the dielectric cavity. The differing behaviors of NFE and FP in hybrid cavities have varied impacts on relevant nanophotonic applications such as fluorescence, Raman scattering and enhanced light-matter interactions.

Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden.

BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. OBJECTIVE: We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. STUDY DESIGN: A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. RESULTS: The use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99), and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P<.002), and 1.63 additional cases per 10,000 person-years. CONCLUSION: The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It is important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.

A modified drag coefficient model for calculating the terminal settling velocity and horizontal diffusion distance of irregular plume particles in deep-sea mining.

Deep-sea mining inevitably produces plumes, which will pose a serious threat to the marine environment with the continuous movement and diffusion of plumes along with ocean currents. The terminal settling velocity (wt) of irregular particles is one of the crucial factors for determining the plumes' diffusion range. It is generally calculated by drag coefficient (CD), while most existing CD models only consider single shape characteristic parameter or have a smaller range of Reynolds number (Re). In this study, a new shape factor (γ) of irregular particles is proposed by considering the thickness (one-dimension), the projected area (two-dimension), and the surface area (three-dimension) of irregular particles as well as their coupling effect to establish a modified CD model for calculating the wt. A modified Gaussian plume model is proposed to predict the horizontal diffusion distance of the plume particles by considering the settling velocity and diffusion effect of irregular particles. Research results show that the wt increases nearly linearly, with a gradually decreased slope and slightly then greatly with the increasing of γ, dp (diameter) and ρp (density), respectively. The modified CD model is verified to be more valid with a wider application range (Re < 3×105) than five existing CD models by the test results. The larger the ρp or dp, the larger the wt and thus the smaller the Sh. This study could provide a theoretical basis for calculating the plume diffusion range to further study the impact of deep-sea mining on the ocean environment.

MXene@c-MWCNT Adhesive Silica Nanofiber Membranes Enhancing Electromagnetic Interference Shielding and Thermal Insulation Performance in Extreme Environments.

A lightweight flexible thermally stable composite is fabricated by combining silica nanofiber membranes (SNM) with MXene@c-MWCNT hybrid film. The flexible SNM with outstanding thermal insulation are prepared from tetraethyl orthosilicate hydrolysis and condensation by electrospinning and high-temperature calcination; the MXene@c-MWCNTx:y films are prepared by vacuum filtration technology. In particular, the SNM and MXene@c-MWCNT6:4 as one unit layer (SMC1) are bonded together with 5 wt% polyvinyl alcohol (PVA) solution, which exhibits low thermal conductivity (0.066 W m-1 K-1) and good electromagnetic interference (EMI) shielding performance (average EMI SET, 37.8 dB). With the increase in functional unit layer, the overall thermal insulation performance of the whole composite film (SMCx) remains stable, and EMI shielding performance is greatly improved, especially for SMC3 with three unit layers, the average EMI SET is as high as 55.4 dB. In addition, the organic combination of rigid SNM and tough MXene@c-MWCNT6:4 makes SMCx exhibit good mechanical tensile strength. Importantly, SMCx exhibit stable EMI shielding and excellent thermal insulation even in extreme heat and cold environment. Therefore, this work provides a novel design idea and important reference value for EMI shielding and thermal insulation components used in extreme environmental protection equipment in the future.

A p21-ATD mouse model for monitoring and eliminating senescent cells and its application in liver regeneration post injury.

Cellular senescence associates with pathological aging and tissue dysfunctions. Studies utilizing mouse models for cell lineage tracings have emphasized the importance of senescence heterogeneity in different organs and cell types. Here, we constructed a p21- (Akaluc - tdTomato - Diphtheria Toxin Receptor [DTR]) (ATD) mouse model to specifically study the undefined mechanism for p21-expressing senescent cells in the aged and liver injury animals. The successful expressions of these genes enabled in vitro flow cytometric sorting, in vivo tracing, and elimination of p21-expressing senescent cells. During the natural aging process, p21-expressing cells were found in various tissues of p21-ATD mice. Eliminating p21-expressing cells in the aged p21-ATD mice recovered their multiple biological functions. p21-ATD/Fah-/- mice, bred from p21-ATD mice and fumarylacetoacetate hydrolase (Fah)-/- mice of liver injury, showed that the majority of their senescent hepatocytes were the phenotype of p21+ rather than p16+. Furthermore, eliminating the p21-expressing hepatocytes significantly promoted the engraftment of grafted hepatocytes and facilitated liver repopulation, resulting in significant recovery from liver injury. Our p21-ATD mouse model serves as an optimal model for studying the pattern and function of p21-expressing senescent cells under the physical and pathological conditions during aging.

Threonine dehydrogenase regulates neutrophil homeostasis but not H3K4me3 levels in zebrafish.

l-threonine dehydrogenase (Tdh) is an enzyme that links threonine metabolism to epigenetic modifications and mitochondria biogenesis. In vitro studies show that it is critical for the regulation of trimethylation of histone H3 lysine 4 (H3K4me3) levels and cell fate determination of mouse embryonic stem cells (mESCs). However, whether Tdh regulates a developmental process in vivo and, if it does, whether it also primarily regulates H3K4me3 levels in this process as it does in mESCs, remains elusive. Here, we revealed that, in zebrafish hematopoiesis, tdh is preferentially expressed in neutrophils. Knockout of tdh causes a decrease in neutrophil number and slightly suppresses their acute injury-induced migration, but, unlike the mESCs, the level of H3K4me3 is not evidently reduced in neutrophils sorted from the kidney marrow of adult tdh-null zebrafish. These phenotypes are dependent on the enzymatic activity of Tdh. Importantly, a soluble supplement of nutrients that are able to fuel the acetyl-CoA pool, such as pyruvate, glucose and branched-chain amino acids, is sufficient to rescue the reduction in neutrophils caused by tdh deletion. In summary, our study presents evidence for the functional requirement of Tdh-mediated threonine metabolism in a developmental process in vivo. It also provides an animal model for investigating the nutritional regulation of myelopoiesis and immune response, as well as a useful tool for high-throughput drug/nutrition screening.

[Cases Analysis of Hemoglobin H Disease Caused by HBA2:c.2T>C and HBA2:c.2delT Mutations].

OBJECTIVE: To investigate two cases of rare pathogenic genes, initiation codon mutations in HBA2 gene, combined with Southeast Asian deletion and their family members to understand the relationship of HBA2:c.2T>C and HBA2:c.2delT mutations with clinical phenotype. METHODS: The peripheral blood of family members was obtained for blood cell analysis and capillary electrophoresis hemoglobin analysis. Gap-PCR and reverse dot blotting (RDB) were used to detect common types of mutations in ɑ-thalassaemia gene. Sanger sequencing was used to analyze HBA1 and HBA2 gene sequence. RESULTS: Two proband genotypes were identified as --SEA/αα with HBA2:c.2T>C and --SEA/αα with HBA2:c.2delT. HBA2:c.2T>C/WT and HBA2:c.2delT/WT was detected in family members. They all presented with microcytic hypochromic anemia. CONCLUSION: When HBA2:c.2T>C and HBA2:c.2delT are heterozygous that can lead to static α-thalassemia phenotype, and when combined with mild α-thalassemia, they can lead to the clinical manifestations of hemoglobin H disease. This study provides a basis for genetic counseling.