The I7L protein of African swine fever virus is involved in viral pathogenicity by antagonizing the IFN-γ-triggered JAK-STAT signaling pathway through inhibiting the phosphorylation of STAT1.

Cell-passage-adapted strains of African swine fever virus (ASFV) typically exhibit substantial genomic alterations and attenuated virulence in pigs. We have indicated that the human embryonic kidney (HEK293T) cells-adapted ASFV strain underwent genetic alterations and the I7L gene in the right variable region was deleted compared with the ASFV HLJ/2018 strain (ASFV-WT). A recent study has revealed that the deletion of the I7L-I11L genes results in attenuation of virulent ASFV in vivo, but the underlying mechanism remains largely unknown. Therefore, we hypothesized that the deletion of the I7L gene may be related to the pathogenicity of ASFV in pigs. We generated the I7L gene-deleted ASFV mutant (ASFV-ΔI7L) and found that the I7L gene deletion does not influence the replication of ASFV in primary porcine alveolar macrophages (PAMs). Using transcriptome sequencing analysis, we identified that the differentially expressed genes in the PAMs infected with ASFV-ΔI7L were mainly involved in antiviral immune responses induced by interferon gamma (IFN-γ) compared with those in the ASFV-WT-infected PAMs. Meanwhile, we further confirmed that the I7L protein (pI7L) suppressed the IFN-γ-triggered JAK-STAT signaling pathway. Mechanistically, pI7L interacts with STAT1 and inhibits its phosphorylation and homodimerization, which depends on the tyrosine at position 98 (Y98) of pI7L, thereby preventing the nuclear translocation of STAT1 and leading to the decreased production of IFN-γ-stimulated genes. Importantly, ASFV-ΔI7L exhibited reduced replication and virulence compared with ASFV-WT in pigs, likely due to the increased production of IFN-γ-stimulated genes, indicating that pI7L is involved in the virulence of ASFV. Taken together, our findings demonstrate that pI7L is associated with pathogenicity and antagonizes the IFN-γ-triggered JAK-STAT signaling pathway via inhibiting the phosphorylation and homodimerization of STAT1 depending on the Y98 residue of pI7L and the Src homology 2 domain of STAT1, which provides more information for understanding the immunoevasion strategies and designing the live attenuated vaccines against ASFV infection.

Impairments in endogenous AMPA receptor dynamics correlates with learning deficits in Alzheimer's disease model mice.

AMPA receptors (AMPARs) play a critical role in synaptic plasticity and learning and memory, and dysfunction or dysregulation of AMPARs could lead to various neurological and psychiatric disorders, such as Alzheimer's disease (AD). However, the dynamics and/or longitudinal changes of AMPARs in vivo during AD pathogenesis remain elusive. Here, employing 5xFAD SEP-GluA1 KI mice, we investigated endogenous AMPA receptor dynamics in a whisker deflection-associated Go/No-go learning paradigm. We found a significant increase in synaptosomal AMPA receptor subunits GluA1 in WT mice after learning, while no such changes were detected in 7-mo-old 5xFAD mice. Daily training led to an increase in endogenous spine surface GluA1 in Control mice, while this increase was absent in 5xFAD-KI mice which correlates with its learning defects in Go/No-go paradigm. Furthermore, we demonstrated that the onset of abnormal AMPAR dynamics corresponds temporally with microglia and astrocyte overactivation. Our results have shown that impairments in endogenous AMPA receptor dynamics play an important role in learning deficits in 5xFAD mice and AD pathogenesis.

17ß-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17ß-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17ß-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7's miRNAs into EVs. In multiple patient cohorts, we observed increased levels of let-7a-5p and let-7d-5p in EVs derived from the blood of premenopausal ER+ BC patients, and elevated EV levels in patients with high BMI, both conditions associated with higher levels of 17ß-estradiol. In brief, we identified a unique estrogen-driven mechanism by which ER+ BC cells eliminate tumor suppressor miRNAs in EVs, with effects on modulating tumor-associated macrophages in the microenvironment.

NLRP1 restricts porcine deltacoronavirus infection via IL-11 inhibiting the phosphorylation of the ERK signaling pathway.

Continuously emerging highly pathogenic coronaviruses remain a major threat to human and animal health. Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes large-scale outbreaks of severe diarrhea disease in piglets. Unlike other porcine coronaviruses, PDCoV has a wide range of species tissue tropism, including primary human cells, which poses a significant risk of cross-species transmission. Nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) has a key role in linking host innate immunity to microbes and the regulation of inflammatory pathways. We now report a role for NLRP1 in the control of PDCoV infection. Overexpression of NLRP1 remarkably suppressed PDCoV infection, whereas knockout of NLRP1 led to a significant increase in PDCoV replication. A mechanistic study revealed that NLRP1 suppressed PDCoV replication in cells by upregulating IL-11 expression, which in turn inhibited the phosphorylation of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor U0126 effectively hindered PDCoV replication in pigs. Together, our results demonstrated that NLRP1 exerted an anti-PDCoV effect by IL-11-mediated inhibition of the phosphorylation of the ERK signaling pathway, providing a novel antiviral signal axis of NLRP1-IL-11-ERK. This study expands our understanding of the regulatory network of NLRP1 in the host defense against virus infection and provides a new insight into the treatment of coronaviruses and the development of corresponding drugs.IMPORTANCECoronavirus, which mainly infects gastrointestinal and respiratory epithelial cells in vivo, poses a huge threat to both humans and animals. Although porcine deltacoronavirus (PDCoV) is known to primarily cause fatal diarrhea in piglets, reports detected in plasma samples from Haitian children emphasize the potential risk of animal-to-human spillover. Finding effective therapeutics against coronaviruses is crucial for controlling viral infection. Nucleotide-binding oligomerization-like receptor (NLR) family pyrin domain-containing 1 (NLRP1), a key regulatory factor in the innate immune system, is highly expressed in epithelial cells and associated with the pathogenesis of viruses. We demonstrate here that NLRP1 inhibits the infection of the intestinal coronavirus PDCoV through IL-11-mediated phosphorylation inhibition of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor can control the infection of PDCoV in pigs. Our study emphasizes the importance of NLRP1 as an immune regulatory factor and may open up new avenues for the treatment of coronavirus infection.

Processing bulk natural wood into a high-performance structural material.

Synthetic structural materials with exceptional mechanical performance suffer from either large weight and adverse environmental impact (for example, steels and alloys) or complex manufacturing processes and thus high cost (for example, polymer-based and biomimetic composites). Natural wood is a low-cost and abundant material and has been used for millennia as a structural material for building and furniture construction. However, the mechanical performance of natural wood (its strength and toughness) is unsatisfactory for many advanced engineering structures and applications. Pre-treatment with steam, heat, ammonia or cold rolling followed by densification has led to the enhanced mechanical performance of natural wood. However, the existing methods result in incomplete densification and lack dimensional stability, particularly in response to humid environments, and wood treated in these ways can expand and weaken. Here we report a simple and effective strategy to transform bulk natural wood directly into a high-performance structural material with a more than tenfold increase in strength, toughness and ballistic resistance and with greater dimensional stability. Our two-step process involves the partial removal of lignin and hemicellulose from the natural wood via a boiling process in an aqueous mixture of NaOH and Na2SO3 followed by hot-pressing, leading to the total collapse of cell walls and the complete densification of the natural wood with highly aligned cellulose nanofibres. This strategy is shown to be universally effective for various species of wood. Our processed wood has a specific strength higher than that of most structural metals and alloys, making it a low-cost, high-performance, lightweight alternative.

Comparison of knee joint and temporomandibular joint development in pig embryos.

Although the knee joint (KNJ) and temporomandibular joint (TMJ) all belong to the synovial joint, there are many differences in developmental origin, joint structure and articular cartilage type. Studies of joint development in embryos have been performed, mainly using poultry and rodents. However, KNJ and TMJ in poultry and rodents differ from those in humans in several ways. Very little work has been done on the embryonic development of KNJ and TMJ in large mammals. Several studies have shown that pigs are ideal animals for embryonic development research. Embryonic day 30 (E30), E35, E45, E55, E75, E90, Postnatal day 0 (P0) and Postnatal day 30 (P30) embryos/fetuses from the pigs were used for this study. The results showed that KNJ develops earlier than TMJ. Only one mesenchymal condensate of KNJ is formed on E30, while two mesenchymal condensates of TMJ are present on E35. All structures of KNJ and TMJ were formed on E45. The growth plate of KNJ begins to develop on E45 and becomes more pronounced from E55 to P30. From E75 to E90, more and more vascular-rich cartilage canals form in the cartilage regions of both joints. The cartilaginous canal of the TMJ divides the condyle into sections along the longitudinal axis of the condyle. This arrangement of cartilaginous canal was not found in the KNJ. The chondrification of KNJ precedes that of TMJ. Ossification of the knee condyle occurs gradually from the middle to the periphery, while that of the TMJ occurs gradually from the base of the mandibular condyle. In the KNJ, the ossification of the articular condyle is evident from P0 to P30, and the growth plate is completely formed on P30. In the TMJ, the cartilage layer of condyle becomes thinner from P0 to P30. There is no growth plate formation in TMJ during its entire development. There is no growth plate formation in the TMJ throughout its development. The condyle may be the developmental center of the TMJ. The chondrocytes and hypertrophic chondrocytes of the growth plate are densely arranged. The condylar chondrocytes of TMJ are scattered, while the hypertrophic chondrocytes are arranged. Embryonic development of KNJ and TMJ in pigs is an important bridge for translating the results of rodent studies to medical applications.

Quinclorac-resistant Echinochloa spp. promoted growth and reproduction of Laodelphax striatellus (Hemiptera: Delphacidae) probably by providing more nutrients and stable environment.

Rice is an important agricultural crop that faces serious challenges from pathogens, pests, and weeds during growth stages. Meanwhile, these organisms would interact with each other to increase the level of destruction. The previous studies showed that barnyard grass (Echinochloa spp) could be used as a temporary host to increase infestation of small brown planthopper (SBPH, Laodelphax striatellus), which is one of the main polyphagous pests. Herbicides are widely used to control weeds that induce resistance development. However, little is known about the effects of increased weed resistance on insect species. In this study, we investigated the effect of quinclorac-resistant and sensitive biotypes of barnyard grass (Echinochloa crus-galli var. zelayensis; Echinochloa crus-pavonis Schult) and rice plants (Wuyujing 3) on the ecological fitness of SBPH and examined physiological indicators of plants and SBPH to explore the mechanism. Our results showed that the growth and reproduction of SBPH promoted significantly reared on quinclorac-resistant barnyard grass. From the perspectives of oxidative stress response, the activities of peroxidase (POD) increased and the activities of catalase (CAT), mixed-functional oxidase (MFO), and carboxylesterase (CarE) decreased in SBPH reared on resistant barnyard grass. Combined with the increased amino acid contents (threonine, serine, methionine, and alanine) of resistant barnyard grass E. crus-pavonis, we speculate that quinclorac-resistant barnyard grass probably provides SBPH with a more suitable environment, thus increasing the risk of SBPH.

Novel CaMKII-δ Inhibitor Hesperadin Exerts Dual Functions to Ameliorate Cardiac Ischemia/Reperfusion Injury and Inhibit Tumor Growth.

BACKGROUND: Cardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease, the leading cause of morbidity and mortality worldwide. At present, there is no effective therapy for reducing cardiac I/R injury. CaMKII (Ca2+/calmodulin-dependent kinase II) plays a pivotal role in the pathogenesis of severe heart conditions, including I/R injury. Pharmacological inhibition of CaMKII is an important strategy in the protection against myocardial damage and cardiac diseases. To date, there is no drug targeting CaMKII for the clinical therapy of heart disease. Furthermore, at present, there is no selective inhibitor of CaMKII-δ, the major CaMKII isoform in the heart. METHODS: A small-molecule kinase inhibitor library and a high-throughput screening system for the kinase activity assay of CaMKII-δ9 (the most abundant CaMKII-δ splice variant in human heart) were used to screen for CaMKII-δ inhibitors. Using cultured neonatal rat ventricular myocytes, human embryonic stem cell-derived cardiomyocytes, and in vivo mouse models, in conjunction with myocardial injury induced by I/R (or hypoxia/reoxygenation) and CaMKII-δ9 overexpression, we sought to investigate the protection of hesperadin against cardiomyocyte death and cardiac diseases. BALB/c nude mice with xenografted tumors of human cancer cells were used to evaluate the in vivo antitumor effect of hesperadin. RESULTS: Based on the small-molecule kinase inhibitor library and screening system, we found that hesperadin, an Aurora B kinase inhibitor with antitumor activity in vitro, directly bound to CaMKII-δ and specifically blocked its activation in an ATP-competitive manner. Hesperadin functionally ameliorated both I/R- and overexpressed CaMKII-δ9-induced cardiomyocyte death, myocardial damage, and heart failure in both rodents and human embryonic stem cell-derived cardiomyocytes. In addition, in an in vivo BALB/c nude mouse model with xenografted tumors of human cancer cells, hesperadin delayed tumor growth without inducing cardiomyocyte death or cardiac injury. CONCLUSIONS: Here, we identified hesperadin as a specific small-molecule inhibitor of CaMKII-δ with dual functions of cardioprotective and antitumor effects. These findings not only suggest that hesperadin is a promising leading compound for clinical therapy of cardiac I/R injury and heart failure, but also provide a strategy for the joint therapy of cancer and cardiovascular disease caused by anticancer treatment.

Novel Bismuth Nanoflowers Encapsulated in N-Doped Carbon Frameworks as Superb Composite Anodes for High-Performance Sodium-Ion Batteries.

Bismuth (Bi) has attracted attention as a promising anode for sodium-ion batteries (SIBs) owing to its suitable potential and high theoretical capacity. However, the large volumetric changes during cycling leads to severe degradation of electrochemical performance and limits its practical application. Herein, Bi nanoflowers are encapsulated in N-doped carbon frameworks to construct a novel Bi@NC composite via a facile solvothermal method and carbonization strategy. The well-designed composite structure endows the Bi@NC with uniformly dispersed Bi nanoflowers to alleviate the attenuation while the N-doped carbon frameworks improve the conductivity and ion transport of the whole electrode. As for sodium-ion half-cell, the electrode exhibits a high specific capacity (384.8 mAh g-1 at 0.1 A g-1 ) and excellent rate performance (341.5 mAh g-1 at 10 A g-1 ), and the capacity retention rate still remains at 94.9% after 5000 cycles at 10 A g-1 . Furthermore, the assembled full-cell with Na3 V2 (PO4 )3 cathode and Bi@NC anode can deliver a high capacity of 251.5 mAh g-1 at 0.1 A g-1 , and its capacity attenuates only 0.009% in each cycle after 2000 times at 5.0 A g-1 . This work offers a convenient, low-cost, and eco-friendliness approach for high-performance electrodes in the field of sodium ion electrochemical storage technology.

The Unique Glycosylation at Position 986 on the E2 Glycoprotein of Classical Swine Fever Virus Is Responsible for Viral Attenuation and Protection against Lethal Challenge.

Classical swine fever (CSF) is an economically important disease of pigs caused by classical swine fever virus (CSFV). The live attenuated vaccine C-strain (also called HCLV strain) against CSF was produced by multiple passages of a highly virulent strain in rabbits. However, the molecular determinants for its attenuation and protection remain unclear. In this study, we identified a unique glycosylation at position 986 (986NYT988) on the E2 glycoprotein Domain IV of C-strain but not (986NYA988) the highly virulent CSFV Shimen strain. We evaluated the infectivity, virulence, and protective efficacy of the C-strain-based mutant rHCLV-T988A lacking the glycosylation and Shimen strain mutant rShimen-A988T acquiring an additional glycosylation at position 986. rShimen-A988T showed a significantly decreased viral replication ability in SK6 cells, while rHCLV-T988A exhibited a growth kinetics indistinguishable from that of C-strain. Removal of the C-strain glycosylation site does not affect viral replication in rabbits and the attenuated phenotype in pigs. However, rShimen-A988T was attenuated and protected the pigs from a lethal challenge at 14 days postinoculation. In contrast, the rHCLV-T988A-inoculated pigs showed transient fever, a few clinical signs, and pathological changes in the spleens upon challenge with the Shimen strain. Mechanistic investigations revealed that the unique glycosylation at position 986 influences viral spreading, alters the formation of E2 homodimers, and leads to increased production of neutralizing antibodies. Collectively, our data for the first time demonstrate that the unique glycosylation at position 986 on the E2 glycoprotein is responsible for viral attenuation and protection. IMPORTANCE Viral glycoproteins involve in infectivity, virulence, and host immune responses. Deglycosylation on the Erns, E1, or E2 glycoprotein of highly virulent classical swine fever virus (CSFV) attenuated viral virulence in pigs, indicating that the glycosylation contributes to the pathogenicity of the highly virulent strain. However, the effects of the glycosylation on the C-strain E2 glycoprotein on viral infectivity in cells, viral attenuation, and protection in pigs have not been elucidated. This study demonstrates the unique glycosylation at position 986 on the C-strain E2 glycoprotein. C-strain mutant removing the glycosylation at the site provides only partial protection against CSFV challenge. Remarkably, the addition of the glycan to E2 of the highly virulent Shimen strain attenuates the viral virulence and confers complete protection against the lethal challenge in pigs. Our findings provide a new insight into the contribution of the glycosylation to the virus attenuation and protection.

The A137R Protein of African Swine Fever Virus Inhibits Type I Interferon Production via the Autophagy-Mediated Lysosomal Degradation of TBK1.

African swine fever is a lethal hemorrhagic disease of pigs caused by African swine fever virus (ASFV), which greatly threatens the pig industry in many countries. Deletion of virulence-associated genes to develop live attenuated ASF vaccines is considered to be a promising strategy. A recent study has revealed that the A137R gene deletion results in ASFV attenuation, but the underlying mechanism remains unknown. To elucidate the mechanism of the A137R gene regulating ASFV virulence, an ASFV mutant with the A137R gene deleted (ASFV-ΔA137R) was generated based on the wild-type ASFV HLJ/2018 strain (ASFV-WT). Using transcriptome sequencing analysis, we found that ASFV-ΔA137R induced higher type I interferon (IFN) production in primary porcine alveolar macrophages (PAMs) than did ASFV-WT. Overexpression of the A137R protein (pA137R) inhibited the activation of IFN-ß or IFN-stimulated response element. Mechanistically, pA137R interacts with TANK-binding kinase 1 (TBK1) and promotes the autophagy-mediated lysosomal degradation of TBK1, which blocks the nuclear translocation of interferon regulator factor 3, leading to decreased type I IFN production. Taken together, our findings clarify that pA137R negatively regulates the cGAS-STING-mediated IFN-ß signaling pathway via the autophagy-mediated lysosomal degradation of TBK1, which highlights the involvement of pA137R regulating ASFV virulence. IMPORTANCE African swine fever (ASF) is a lethal viral disease of pigs caused by African swine fever virus (ASFV). No commercial vaccines and antiviral treatments are available for the prevention and control of the disease. Several virulence-associated genes of ASFV have been identified, but the underlying attenuation mechanisms are not clear. Compared with the virulent parental ASFV, the A137R gene-deleted ASFV mutant promoted the expression of type I interferon (IFN) in primary porcine alveolar macrophages. Further analysis indicated that the A137R protein negatively regulated the cGAS-STING-mediated IFN-ß signaling pathway through targeting TANK-binding kinase 1 (TBK1) for autophagy-mediated lysosomal degradation. This study not only facilitates the understanding of ASFV immunoevasion strategies, but also provides new clues to the development of live attenuated ASF vaccines.

Mooring Stone-Like Arg114 Pulls Diverse Bulged Peptides: First Insight into African Swine Fever Virus-Derived T Cell Epitopes Presented by Swine Major Histocompatibility Complex Class I.

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), which is a devastating pig disease threatening the global pork industry. However, currently, no commercial vaccines are available. During the pig immune response, major histocompatibility complex class I (MHC-I) molecules select viral peptide epitopes and present them to host cytotoxic T lymphocytes, thereby playing critical roles in eliminating viral infections. Here, we screened peptides derived from ASFV and determined the molecular basis of ASFV-derived peptides presented by the swine leukocyte antigen 1*0101 (SLA-1*0101). We found that peptide binding in SLA-1*0101 differs from the traditional mammalian binding patterns. Unlike the typical B and F pockets used by the common MHC-I molecule, SLA-1*0101 uses the D and F pockets as major peptide anchor pockets. Furthermore, the conformationally stable Arg114 residue located in the peptide-binding groove (PBG) was highly selective for the peptides. Arg114 draws negatively charged residues at positions P5 to P7 of the peptides, which led to multiple bulged conformations of different peptides binding to SLA-1*0101 and creating diversity for T cell receptor (TCR) docking. Thus, the solid Arg114 residue acts as a "mooring stone" and pulls the peptides into the PBG of SLA-1*0101. Notably, the T cell recognition and activation of p72-derived peptides were verified by SLA-1*0101 tetramer-based flow cytometry in peripheral blood mononuclear cells (PBMCs) of the donor pigs. These results refresh our understanding of MHC-I molecular anchor peptides and provide new insights into vaccine development for the prevention and control of ASF. IMPORTANCE The spread of African swine fever virus (ASFV) has caused enormous losses to the pork industry worldwide. Here, a series of ASFV-derived peptides were identified, which could bind to swine leukocyte antigen 1*0101 (SLA-1*0101), a prevalent SLA allele among Yorkshire pigs. The crystal structure of four ASFV-derived peptides and one foot-and-mouth disease virus (FMDV)-derived peptide complexed with SLA-1*0101 revealed an unusual peptide anchoring mode of SLA-1*0101 with D and F pockets as anchoring pockets. Negatively charged residues are preferred within the middle portion of SLA-1*0101-binding peptides. Notably, we determined an unexpected role of Arg114 of SLA-1*0101 as a "mooring stone" which pulls the peptide anchoring into the PBG in diverse "M"- or "n"-shaped conformation. Furthermore, T cells from donor pigs could activate through the recognition of ASFV-derived peptides. Our study sheds light on the uncommon presentation of ASFV peptides by swine MHC-I and benefits the development of ASF vaccines.

Dispersion-boosting wideband electromagnetic transparency under extreme angles for TE-polarized waves.

Half-wave wall is the most common method of achieving electromagnetic (EM) transparency. Transmission windows can be formed when reflected waves are out of phase. Due to the interference mechanism, these windows are dependent on the frequency and incident angle of EM waves, leading to limited bandwidth, especially under extreme angles. In this letter, we propose to extend the bandwidth of the transmission window under extreme angles by utilizing dispersion. To this end, long metallic wires are embedded into the half-wave wall matrix, without increasing the physical thickness. Due to the plasma-like behavior of metallic wires under TE-polarization, the effective permittivity of the half-wave wall, rather than keeping constant, increases with frequency nonlinearly. Such a dispersion will boost wideband transparency in two aspects. On one hand, an additional transmission window will be generated where the effective permittivity equals that of the air; on the other hand, the 1st- and 2nd-order half-wave windows will be made quite closer. By tailoring the dispersion, the three windows can be merged to enable wideband transparency under extreme incident angles. A proof-of-principle prototype was designed, fabricated, and measured to verify this strategy. Both simulated and measured results show that the prototype can operate in the whole Ku-band under incident angle [70°, 85°] for TE-polarized waves. This work provides an effective method of achieving wideband EM transparency under extreme angles and may find applications in radar, communications, and others.

Risk factors for the development of severe breast cancer-related lymphedema: a retrospective cohort study.

BACKGROUND: Severe lymphedema presents a challenge in terms of treatment due to the significant formation of scar tissue that accompanies it. The aim of this study was to identify intraoperative and preoperative risk factors of severe lymphedema and to develop a nomogram for estimating the risk of severe lymphedema within 3 years of surgery. METHOD: Data was collected from a retrospective cohort of 326 patients with BCRL at the Zhejiang Cancer Hospital from November 2015 to November 2018. Univariate and multivariate logistic regression analysis was conducted to identify predictive indicators of severe lymphedema. A nomogram was developed to further improve the clinical applicability. RESULTS: In the retrospective cohort, the ratio of severe/non-severe lymphedema within 3 years of surgery was 1:3. Independent risk factors for severe lymphedema were determined to be age, positive lymph nodes, interpectoral (Rotter's) lymph nodes (IPNs) dissection, and educational level. IPNs dissection was found to contribute greatly to the development of severe lymphedema with a higher odds ratio (7.76; 95% CI: 3.87-15.54) than other risk factors. A nomogram was developed by integrating age, positive lymph nodes, IPNs dissection, and educational level, which yielded a C-index of 0.810 and 0.681 in the training and validation cohort, respectively. This suggested a moderate performance of the nomogram in predicting the risk of severe lymphedema within 3 years of surgery. The cut-off values of the low-, medium- and high-risk probabilities were 0.0876 and 0.3498, and the severe lymphedema exhibited a significantly higher risk probability as compared with the non-severe lymphedema. CONCLUSION: This study identified the risk factors of severe lymphedema and highlighted the substantial contribution of IPNs dissection to the severity of lymphedema.

Urinary orosomucoid and retinol binding protein levels as early diagnostic markers for diabetic kidney Disease.

BACKGROUND: Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes, which has been a major cause of end-stage renal failure. Diagnosing diabetic kidney disease is important to prevent long-term kidney damage and determine the prognosis of patients with diabetes. In this study, we investigated the clinical significance of combined detection of urine orosomucoid and retinol-binding protein for early diagnosis of diabetic kidney disease. METHODS: We recruited 72 newly diagnosed patients with type 2 diabetes and 34 healthy persons from August 2016 to July 2018 at the First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital). Using the Mogensen grading criteria, participants were classified as having diabetes or diabetic kidney disease, and healthy persons constituted the control group. Urine orosomucoid and retinol-binding protein levels were measured and correlated with other variables. RESULTS: With the aggravation of renal damage, the level of urinary mucoid protein gradually increased. Urinary retinol-binding protein and microalbumin levels were significantly higher in the diabetes group than in control and nephropathy groups. Orosomucoid and retinol-binding protein might be independent risk factors for diabetes and diabetic kidney disease. Urinary orosomucoid significantly correlated with retinol-binding protein and microalbumin levels in the diabetic kidney disease group. CONCLUSION: Elevated urine orosomucoid and retinol-binding protein levels can be detected in the early stages of type 2 diabetic kidney disease. Both of these markers are important for diabetic kidney disease detection and early treatment.

Edge-Nitrogen Enriched Porous Carbon Nanosheets Anodes with Enlarged Interlayer Distance for Fast Charging Sodium-Ion Batteries.

The application of nitrogen-doped porous carbon for sodium-ion batteries (SIBs) has attracted tremendous attention. Herein, a series of edge-nitrogen enriched porous carbon nanosheets (ENPCNs) are synthesized by annealing g-C3 N4 and glucose in a sealed graphite crucible at different temperatures (T = 700, 800, and 900 °C). Surprisingly, under the closed thermal treatment condition, the ENPCNs-T possess a high N-doping level (>12.62 at%) and different carbon interlayer distance ranging from 0.429 to 0.487 nm. By correlating the carbon interlayer distance with the N configurations of ENPCNs-T materials, a reasonable perception of the important influence of pyrrolic N on the increase of carbon interlayer distance is proposed. When applied as anode materials for SIBs, the ENPCNs-800 exhibits a remarkable capacity (294.1 mAh g-1 at 0.1 A g-1 ), excellent rate performance (132.8 mAh g-1 at 10 A g-1 ), and outstanding cycle life (180.6 mAh g-1 at 1 A g-1 after 1000 cycles with a capacity retention of 104.7%). Meanwhile, the characterizations of cyclic voltammetry, galvanostatic intermittent titration technique, and electrochemical impedance spectroscopy demonstrate that the edge-nitrogen doping and enlarged carbon interlayer distance improve the capacity and fast charging performance of ENPCNs-800. Considering the detailed investigation of the Na+ storage mechanism and excellent electrochemical performance of ENPCNs-800, this work can pave a new avenue for the research of SIBs.

Ultra-wideband RCS reduction based on coupling effects between beam diffuse and absorptive structures.

A hybrid design method for broadband radar cross section (RCS) reduction is proposed and successfully demonstrated based on the coupling effects between diffuse and absorptive structures. The reflection energy is distributed into more directions away from the source direction by the one-bit diffuse coding metasurface (CM). The two-layer resistive frequency selective surface (RFSS) is employed in the one-bit CM structure, reducing the amplitude of the co- and cross-polarized reflected waves under circularly polarized wave incidence by converting it into ohmic loss. In addition, the bandwidth of RCS reduction is further broadened through the coupling effects between the metallic patterns and the two-layer RFSS. The coupling effect shows that the absorption rate of the composite structure is significantly improved compared to the only RFSS structure. A lightweight CM loaded with RFSS (the area density is 597 g/m2) was fabricated, analyzed, simulated, and measured. The results show that the proposed mechanism can effectively break the bandwidth constraints of traditional diffusion and absorption methods. Furthermore, the proposed mechanism significantly expands the bandwidth of RCS reduction. The proposed metasurface can achieve a 10 dB RCS reduction in an ultra-wideband from 7.3 to 44.2 GHz with about 143.3% fractional bandwidth. Moreover, the metasurface also has good performances under wide-angle oblique incidences. Under the condition of maintaining lightweight, the design provides an idea for broadening the frequency band.

Tailoring transmission window in a dynamic way with a multi-degree-of-freedom.

With the rapid development of wireless technology, the revolution of tailoring transmission window in dynamic way for the next generation communication systems is urgently required. However, the degree-of-freedom for switching transmission spectra of an effective medium still needs further investigation. Here, we propose a paradigm of solving this difficult academic issue via the method of bias-voltage-driven. Leveraging PIN diodes and varactor diodes into the predesigned positions of plasmonic meta-structures, the macro-control of transmission windows switch and the detailed dispersion manipulation can be separately achieved by synergy modulation of feed networks. Both the numerical simulations and experimental verifications are conducted to support the effectiveness of the proposed method. Significantly, the proposed paradigm presents great potential for applications in intelligent radome, adaptive communication systems, and other EM scenarios with multi-degree-of-freedom.

Polarization meta-converter for dynamic polarization states shifting with broadband characteristic.

Polarization, as an important property of light, has been widely discussed in modern detecting and radar systems. A polarization converter that can be used to achieve dynamic control is regarded as an excellent alternative for implementing the integrated functionalities of communication and stealth. In this work, we propose a paradigm of meta-converter for dynamic polarization states shifting from linear-to-linear (LTL) to linear-to-circular (LTC) polarization. The strategy is achieved by loading voltage-controlled PIN diodes on the double-arrows metallic meta-resonators. The operation modes can be switched by changing the bias voltage. When the PIN diodes are turned on, the polarization meta-converter (PMC) will reflect and convert a linearly polarized electromagnetic (EM) wave into a circularly polarized one in 5.6-15.5 GHz with an axial ratio (AR) below 3dB. When the PIN diodes are turned off, the PMC will reflect and convert a linearly polarized EM wave into the orthogonal counterpart in 7.6-15.5 GHz with a polarization conversion ratio (PCR) over 88%. Simulations and experimental results show a good agreement, which manifests the feasibility of our proposed meta-converter. Moreover, the proposed PMC has great potential for polarization-dependent communication and stealth systems.

Transmission enhancement of a half-wave wall under extreme angles by synergy of double lorentz resonances.

The a half-wave wall is usually adopted as the transparent window for electromagnetic (EM) waves ranging from microwave to optical regimes. Due to the interference nature, the bandwidth of the half-wave wall is usually quite narrow, especially under extreme angles for TE-polarized waves. It is usually contradictory to expand the bandwidth and to keep high transmission. To overcome this contradiction, we propose to extend the transmission bandwidth of half-wave walls under extreme angles by introducing Lorentz-type resonances using metasurfaces. The impedance of the half-wave wall is firstly analyzed. To improve the impedance matching, the impedance below and above the half-wave frequency should be increased. To this end, metallic wires and I-shaped structures are incorporated into the half-wave wall as the mid-layer. Due to the Lorentz-type resonance of the metallic wire, effective permittivity below the half-wave frequency can be reduced while that above the half-wave frequency can be increased due to Lorentz-type resonance of the I-shaped structures, both under large incident angles. In this way, the impedance matching, and thus the transmission, can be improved within an extended band. A proof-of-principle prototype was designed, fabricated, and measured to verify this strategy. Both simulated and measured results show that the prototype can operate in 14.0-19.0GHZ under incident angle [70°, 85°] with significant transmission enhancement for TE-polarized waves. This work provides an effective method of enhancing the transmission of EM waves and may find applications in radomes, IR windows, and others.