Foot-and-mouth disease (FMD) is a highly contagious disease that affects cloven-hoofed animals such as pigs, cattle, and sheep. The disease is caused by the foot-and-mouth disease virus (FMDV) which ...has a non-enveloped virion with icosahedral symmetry that encapsulates a positive-sense, single-stranded RNA genome of ∼8.4 kb. FMDV infection causes obvious immunosuppressive effects on the host. In recent years, studies on the immunosuppressive mechanism of FMDV have become a popular topic. In addition, studies have shown that many FMDV proteins are involved in the regulation of host innate immunity and have revealed mechanisms by which FMDV proteins mediate host innate immunity. In this review, advances in studies on the mechanisms of interaction between FMDV proteins and host innate immunity are summarized to provide a comprehensive understanding of FMDV pathogenesis and the theoretical basis for FMD prevention and control.
African swine fever virus (ASFV) causes acute hemorrhagic infectious disease in pigs. The ASFV genome encodes various proteins that enable the virus to escape innate immunity; however, the underlying ...mechanisms are poorly understood. The present study found that ASFV MGF-360-10L significantly inhibits interferon (IFN)-β-triggered STAT1/2 promoter activation and the production of downstream IFN-stimulated genes (ISGs). ASFV MGF-360-10L deletion (ASFV-Δ10L) replication was impaired compared with the parental ASFV CN/GS/2018 strain, and more ISGs were induced by the ASFV-Δ10L in porcine alveolar macrophages
. We found that MGF-360-10L mainly targets JAK1 and mediates its degradation in a dose-dependent manner. Meanwhile, MGF-360-10L also mediates the K48-linked ubiquitination of JAK1 at lysine residues 245 and 269 by recruiting the E3 ubiquitin ligase HERC5 (HECT and RLD domain-containing E3 ubiquitin protein ligase 5). The virulence of ASFV-Δ10L was significantly lower than that of the parental strain
, which indicates that MGF-360-10L is a novel virulence factor of ASFV. Our findings elaborate the novel mechanism of MGF-360-10L on the STAT1/2 signaling pathway, expanding our understanding of the inhibition of host innate immunity by ASFV-encoded proteins and providing novel insights that could contribute to the development of African swine fever vaccines. IMPORTANCE African swine fever outbreaks remain a concern in some areas. There is no effective drug or commercial vaccine to prevent African swine fever virus (ASFV) infection. In the present study, we found that overexpression of MGF-360-10L strongly inhibited the interferon (IFN)-β-induced STAT1/2 signaling pathway and the production of IFN-stimulated genes (ISGs). Furthermore, we demonstrated that MGF-360-10L mediates the degradation and K48-linked ubiquitination of JAK1 by recruiting the E3 ubiquitin ligase HERC5. The virulence of ASFV with MGF-360-10L deletion was significantly less than parental ASFV CN/GS/2018. Our study identified a new virulence factor and revealed a novel mechanism by which MGF-360-10L inhibits the immune response, thus providing new insights into the vaccination strategies against ASFV.
Foot-and-mouth disease (FMD), induced by the foot-and-mouth disease virus (FMDV), is a highly contagious disease of cloven-hoofed animals. Previous studies have reported that FMDV 3C protease could ...degrade multiple host proteins; however, the degradation mechanism mediated by FMDV 3C is still unclear. Here, we found that transient expression of FMDV 3C degraded various molecules in NF-κB signaling in a dose-dependent manner, and the proteolytic activity of FMDV 3C is important for inducing degradation. Additionally, 3C-overexpression was associated with the induction of apoptosis. In this study, we showed that an apoptosis inhibitor CrmA abolished the ability of 3C to degrade molecules in NF-κB signaling. Further experiments using specific caspase inhibitors confirmed the irrelevance of caspase3, caspase8, and caspase9 activity for degradation induced by 3C. Altogether, these results suggest that FMDV 3C induces the widespread degradation of host proteins through its proteolytic activity and that the apoptosis pathway might be an important strategy to mediate this process. Further exploration of the relationship between apoptosis and degradation induced by 3C could provide novel insights into the pathogenic mechanisms of FMDV.
Knee osteoarthritis (KOA) is a degenerative joint disease which can result in chronic pain and disability. The current interventions available for KOA often fail to provide long-lasting effects, ...highlighting the need for new treatment options that can offer durable benefits. Previous studies have suggested the efficacy of acupuncture for knee osteoarthritis (KOA) with its durability remaining uncertain. In this review, we aimed to investigate the durability of the efficacy after completion of treatment.
We performed thorough searches of PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials from inception to November 4, 2023. The outcomes were assessed at all available time points after completion of treatment. Primary outcomes were changes from baseline in pain and function measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function subscales. Secondary outcomes included response rate, overall pain, the WOMAC stiffness subscale, total WOMAC index, and physical and mental health components of 12/36-item Short-Form Health Survey. A total of 10 randomized controlled trials (RCTs) involving 3221 participants were included. Pooled estimates suggested that acupuncture may offer potential improvements in function and overall pain for 4.5 months post-treatment versus sham acupuncture (SA). Acupuncture may provide durable clinically important pain relief and functional improvement up to 5 months post-treatment versus usual care, and up to 6 months post-treatment versus diclofenac. For acupuncture versus no treatment, one trial with large sample size indicated that improvements in pain and function persisted for 3 months post-treatment, while the other trial reported that significant pain reduction and functional improvement were only observed at the end of the treatment, not at 9 months post-treatment. However, acupuncture as adjunct to exercise-based physical therapy (EPT) showed no superiority to SA as an adjunct to EPT or EPT alone up to 11.25 months after completion of treatment. Acupuncture may provide pain alleviation and functional improvements in KOA patients for 3 to 6 months after completion of treatment with a good safety profile.
Understanding of the evolution of metazoans from their unicellular ancestors is a fundamental question in biology. In contrast to fungi which utilize the Mon1-Ccz1 dimeric complex to activate the ...small GTPase RAB7A, metazoans rely on the Mon1-Ccz1-RMC1 trimeric complex. Here, we report a near-atomic resolution cryogenic-electron microscopy structure of the
Mon1-Ccz1-RMC1 complex. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1 on the surface opposite to the RAB7A-binding site, with many of the RMC1-contacting residues from Mon1 and Ccz1 unique to metazoans, explaining the binding specificity. Significantly, the assembly of RMC1 with Mon1-Ccz1 is required for cellular RAB7A activation, autophagic functions and organismal development in zebrafish. Our studies offer a molecular explanation for the different degree of subunit conservation across species, and provide an excellent example of how metazoan-specific proteins take over existing functions in unicellular organisms.
Time–temperature indicators (TTIs) are cost‐efficient tools that may be used to predict food quality. In this paper, a diffusion TTI was used to predict fruit quality during storage. Both the color ...changing characters of TTI and the quality parameters, including weight loss, soluble solids content, vitamin C content, titratable acidity, and antioxidant capacity of three kinds of fruits (kiwifruit, strawberry, and mango), were investigated for storage temperatures (5, 10, 15, and 20 °C). The relationships between the color changing properties and fruit quality parameters have been built based on the activation energy (Ea). The results showed that the storage temperature and time had significant effects on the color changing of TTI and fruit quality. The RGB value of TTI decreased with time, and the higher the storage temperature, the faster the RGB value reduced. Also, the higher the storage temperature, the faster the fruit quality changed and the poorer they were. Furthermore, all of the differences of Ea between TTI color response and fruit quality change are less than 25 kJ/mol, which indicates that the TTI can be used to predict these fruit quality. Finally, prediction models were built and validated based on the RGB values of TTI. It provides the possibility for low‐cost quality monitoring and has more application potential in food quality predicting.
Practical Application
By monitoring the color change of diffuse time–temperature indicator (TTI) and the quality change of fruit, the feasibility of TTI for fruit quality monitoring was determined and the quality prediction model was established. The diffusion TTI and fruit quality prediction model can realize the monitoring and predicting of fruit quality based on the TTI, which provides a basis for the combination of TTI Quick Response Code and fruit quality monitoring, with a view to achieving fruit quality status by scanning the Quick Response Code of TTI with mobile phones in the future. This method may provide a new solution to monitor the fruit quality during storage and distribution based on visualization technology that can simplify the methods of detecting fruit quality and achieve fast quality detection. It provides the possibility for low‐cost quality monitoring and has more application potential in food quality predicting. Further studies on diffusion TTI are needed to develop its application in more field of food and make the diffusion TTI an intelligent mean for food quality monitoring and predicting.
When a more viscous fluid displaces a less viscous one in porous media, viscous pressure drop stabilizes the displacement front against capillary pressure fluctuation. For this favorable viscous ...ratio conditions, previous studies focused on the front instability under slow flow conditions but did not address competing effects of wettability and flow rate. Here we study how this competition controls displacement patterns. We propose a theoretical model that describes the crossover from fingering to stable flow as a function of invading fluid contact angle θ and capillary number Ca. The phase diagram predicted by the model shows that decreasing θ stabilizes the displacement for θ≥45° and the critical contact angle θc increases with Ca. The boundary between corner flow and cooperative filling for θ < 45° is also described. This work extends the classic phase diagram and has potential applications in predicting CO2 capillary trapping and manipulating wettability to enhance gas/oil displacement efficiency.
Key Points
A theoretical model is proposed to describe the crossover from fingering to stable flow as a function of contact angle and capillary number
The phase diagram predicted by the model shows that decreasing contact angle theta stabilizes the displacement for θ≥45°
The extended phase diagram also captures the boundary between corner flow and cooperative filling for contact angle smaller than 45°
Background
Decellularized extracellular matrixs (dECMs) derived from organs and tissues have emerged as a promising tool, as they encompass the characteristics of an ideal tissue scaffold: complex ...composition, vascular networks and unique tissue‐specific architecture. Consequently, their use has propagated throughout tissue engineering and regenerative medicine. dECM can be easily obtained from various tissues/organs by appropriate decellularization protocolsand is entitled to provide necessary cues to cells homing.
Methods
In this review, we describe the decellularization and sterilization methods that are commonly used in recent research, the effects of these methods upon biologic scaffold material are discussed. Also, we summarize the recent developments of recellularization and vascularization techniques in regeneration medicine. Additionally, dECM preservation methods is mentioned, which provides the basis for the establishment of organ bank.
Results
Biomedical applications and the status of current research developments relating to dECM biomaterials are outlined, including transplantation in vivo, disease models and drug screening, organoid, 3D bioprinting, tissue reconstruction and rehabilitation and cell transplantation and culture. Finally, critical challenges and future developing technologies are discussed.
Conclusions
With the development of tissue engineering and regenerative medicine, dECM will have broader applications in the field of biomedicine in the near future.
To determine the tissue engineering and biomedical application of Decellularized extracellular matrix (dECM), we summarize the acquisition methods, preservation methods, sterilization methods, recellularization and vascularization methods of dECM, and then we further discuss the emerging applications of dECM biomaterials in tissue engineering and regeneration medicine, including in vivo transplantation, disease models construction and drug screening, 3D printing, tissue burns and repair and cell transplantation and culture. Finally, the current bottlenecks of dECM biomaterials and the development technologies that needed to be broken through in the future are discussed. We believe that with the development of tissue engineering and regenerative medicine, dECM will have broader applications in the field of biomedicine in the near future.
It has been reported that the triglyceride-glucose (TyG) index may serve as a simple and credible surrogate marker of insulin resistance (IR). However, its association with macrovascular and ...microvascular damage is unclear. Accordingly, the objective of the present study is to investigate the association of macrovascular and microvascular damage with the TyG index.
A total of 2830 elderly participants from the Northern Shanghai Study (NSS) were enrolled. The TyG index was calculated as lnfasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2. Parameters of vascular damage, including carotid-femoral pulse wave velocity (cf-PWV), brachial-ankle pulse wave velocity (ba-PWV), ankle-brachial index (ABI), carotid intima-media thickness (CMT), carotid plaque, estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR), were measured and calculated.
In univariate logistic regression, an increased TyG index was associated with a higher risk of cf-PWV > 10 m/s, ba-PWV > 1800 cm/s, ABI < 0.9, microalbuminuria (MAU) and chronic kidney disease (CKD). In multivariable logistic regression, there was a significant increase in the risk of cf-PWV > 10 m/s (OR = 1.86, 95% confidence interval 95% CI 1.37-2.53, P
< 0.001), ba-PWV > 1800 cm/s (OR = 1.39, 95% CI 1.05-1.84, P
= 0.02), MAU (OR = 1.61, 95% CI 1.22-2.13, P
< 0.001) and CKD (OR = 1.67, 95% CI 1.10-1.50, P
= 0.02) after adjustment for age, sex, BMI, waist circumference, smoking habit, hypertension, family history of premature CVD, diabetes, HDL-C, LDL-C, insulin therapy and statin therapy. However, no significant relationship was observed between the TyG index and lower extremity atherosclerosis, carotid hypertrophy or carotid plaque.
An elevated TyG index was significantly associated with a higher risk of arterial stiffness and nephric microvascular damage. This conclusion lends support to the clinical significance of the TyG index for the assessment of vascular damage.
Development of high‐performance organic thermoelectric (TE) materials is of vital importance for flexible power generation and solid‐cooling applications. Demonstrated here is the significant ...enhancement in TE performance of selenium‐substituted diketopyrrolopyrrole (DPP) derivatives. Along with strong intermolecular interactions and high Hall mobilities of 1.0–2.3 cm2 V−1 s−1 in doping‐states for polymers, PDPPSe‐12 exhibits a maximum power factor and ZT of up to 364 μW m−1 K−2 and 0.25, respectively. The performance is more than twice that of the sulfur‐based DPP derivative and represents the highest value for p‐type organic thermoelectric materials based on high‐mobility polymers. These results reveal that selenium substitution can serve as a powerful strategy towards rationally designed thermoelectric polymers with state‐of‐the‐art performances.
Packed in: A high‐performance p‐type organic thermoelectric material based on a selenium‐substituted diketopyrrolopyrrole (DPP) polymer was developed. With strong intermolecular interactions and ordered molecular packing, PDPPSe‐12 exhibits high Hall mobilities of 1.0–2.3 cm2 V−1 s−1 in doped states, yielding a maximum PF and ZT value of 364 μW m−1 K−2 and 0.25, respectively.
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