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Abstract The immune system undergoes progressive functional remodeling from neonatal stages to old age. Therefore, understanding how aging shapes immune cell function is vital for precise treatment of patients at different life stages. Here, we constructed the first transcriptomic atlas of immune cells encompassing human lifespan, ranging from newborns to supercentenarians, and comprehensively examined gene expression signatures involving cell signaling, metabolism, differentiation, and functions in all cell types to investigate immune aging changes. By comparing immune cell composition among different age groups, HLA highly expressing NK cells and CD83 positive B cells were identified with high percentages exclusively in the teenager (Tg) group, whereas unknown_T cells were exclusively enriched in the supercentenarian (Sc) group. Notably, we found that the biological age (BA) of pediatric COVID-19 patients with multisystem inflammatory syndrome accelerated aging according to their chronological age (CA). Besides, we proved that inflammatory shift- myeloid abundance and signature correlate with the progression of complications in Kawasaki disease (KD). The shift- myeloid signature was also found to be associated with KD treatment resistance, and effective therapies improve treatment outcomes by reducing this signaling. Finally, based on those age-related immune cell compositions, we developed a novel BA prediction model PHARE ( https://xiazlab.org/phare/ ), which can apply to both scRNA-seq and bulk RNA-seq data. Using this model, we found patients with coronary artery disease (CAD) also exhibit accelerated aging compared to healthy individuals. Overall, our study revealed changes in immune cell proportions and function associated with aging, both in health and disease, and provided a novel tool for successfully capturing features that accelerate or delay aging.

Abstract The application of nanoscale scaffolds has become a promising strategy in vaccine design, with protein-based nanoparticles offering desirable avenues for the biocompatible and efficient delivery of antigens. Here, we presented a novel endogenous capsid-forming protein, activated-regulated cytoskeleton-associated protein (ARC), which could be engineered through the plug-and-play strategy (SpyCatcher3/SpyTag3) for multivalent display of antigens. Combined with the self-assembly capacity and flexible modularity of ARC, ARC-based vaccines elicited robust immune responses against Mpox or SARS-CoV-2, comparable to those induced by ferritin-based vaccines. Additionally, ARC-based nanoparticles functioned as immunostimulants, efficiently stimulating dendritic cells and facilitating germinal center responses. Even without adjuvants, ARC-based vaccines generated protective immune responses in a lethal challenge model. Hence, this study showed the feasibility of ARC as a novel protein-based nanocarrier for multivalent surface display of pathogenic antigens and demonstrated the potential of exploiting recombinant mammalian retrovirus-like protein as a delivery vehicle for bioactive molecules. Graphic Abstract

Previous studies have focused on the impact of individual factors on lane departure warning (LDW) utility during driving. However, comprehensive analysis has not been considered based on multiple variables, such as driver characteristics. This paper aims to propose a methodology in exploring the utility of LDW under varied warning timing situations, focusing on changes in driving style and distraction level to obtain the optimal warning timing matching relationship. A driving simulator experiment with a mixed 4 × 3 factor design was conducted. The design matrix includes four level of secondary task (ST) conditions and three warning timings situations for drivers with various driving styles. To estimate the utility of the LDW system, lane departure duration (LDD) was selected as a time-based measure of utility. Both the Kaplan-Meier method and COX model were applied and compared. Combined with questionnaire results, the results indicate that both driving style and distraction state are significant influence factors. Generally, the results suggest that the more aggressive drivers lead to the more severe lane departure behavior and they preferred late warning. In terms of distraction state, the LDD increases with the level of ST remarkably. This implies that the earlier warning timing should be given for the higher-level distraction state condition. It was also observed that adaptive warning timing is needed based on the analysis of the interactive effect among multiple variables. The results provide empirical data for the optimization of LDW system design.

Abstract Rift Valley fever virus (RVFV) is listed as a priority pathogen by the World Health Organization (WHO) because it causes serious and fatal disease in humans, and there are currently no effective countermeasures. Therefore, it is urgent to develop a safe and efficacious vaccine. Here, we developed six nucleotide-modified mRNA vaccines encoding different regions of the Gn and Gc proteins of RVFV encapsulated in lipid nanoparticles, compared their ability to induce immune responses in mice and found that mRNA vaccine encoding the full-length Gn and Gc proteins had the strongest ability to induce cellular and humoral immune responses. IFNAR(−/−) mice vaccinated with mRNA-GnGc were protected from lethal RVFV challenge. In addition, mRNA-GnGc induced high levels of neutralizing antibodies and cellular responses in rhesus macaques, as well as antigen-specific memory B cells. These data demonstrated that mRNA-GnGc is a potent and promising vaccine candidate for RVFV.

Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

Abstract Lizards cannot naturally regenerate limbs but are the closest known relatives of mammals capable of epimorphic tail regrowth. However, the mechanisms regulating lizard blastema formation and chondrogenesis remain unclear. Here, single-cell RNA sequencing analysis of regenerating lizard tails identifies fibroblast and phagocyte populations linked to cartilage formation. Pseudotime trajectory analyses suggest spp1 +-activated fibroblasts as blastema cell sources, with subsets exhibiting sulf1 expression and chondrogenic potential. Tail blastema, but not limb, fibroblasts express sulf1 and form cartilage under Hedgehog signaling regulation. Depletion of phagocytes inhibits blastema formation, but treatment with pericytic phagocyte-conditioned media rescues blastema chondrogenesis and cartilage formation in amputated limbs. The results indicate a hierarchy of phagocyte-induced fibroblast gene activations during lizard blastema formation, culminating in sulf1 + pro-chondrogenic populations singularly responsive to Hedgehog signaling. These properties distinguish lizard blastema cells from homeostatic and injury-stimulated fibroblasts and indicate potential actionable targets for inducing regeneration in other species, including humans.

Household waste contributes significantly to global greenhouse gas (GHG) emissions, and waste classification is crucial for reducing emissions. This study focuses on Beijing and utilizes life cycle assessment (LCA) and material flow analysis (MFA) to calculate GHG emissions in waste management systems and quantify emission reduction potential of different measures. The results show that net emissions from the classification system in 2021 are 116.77 kg CO2-eq/t waste, reducing 61.82 % compared to the traditional mixed collection and transportation system. Waste volume, classification efficiency, and treatment strategies are the primary factors affecting emissions in classification systems. Recycling is identified as effective treatment methods. Three scenarios are designed to explore emission pathway of the system toward 2060. In the business-as-usual (BAU) Scenario, emissions will continue to grow to 108.57 × 104 t CO2-eq/yr in 2060. In the Classification Efficiency Scenario and the Comprehensive Scenario, emissions in 2060 will be cut to −177.26 × 104 t CO2-eq/yr and −702.00 × 104 t CO2-eq/yr, respectively. These results underscore the critical role of waste classification and recycling in mitigating the negative impacts of increasing waste volume. By 2060, combining waste classification with recycling can offset emissions by 803.51 × 104 t CO2-eq/yr, contributing 99 % to emission reduction potential. Improving classification efficiency and recycling ratio are key measures for achieving this reduction goal. Meanwhile, treatment methods and technologies should prioritize classification and recycling. Aiming at carbon neutrality, the study proposes several recommendations to improve classification systems, including enhancing classification efficiency, optimizing treatment facilities and strategies, and establishing recycling and utilization systems, etc.

IntroductionThe SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required.MethodsWe have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. ResultsThe aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. DiscussionOur findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.

Aluminum (alum) adjuvant is the most extensively used protein subunit vaccine adjuvant, and its effectiveness and safety have been widely recognized. The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant, which directly affects the immune efficacy of the protein vaccine. In our study, we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptor-binding domain (RBD), achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant. This innovative strategy extended the bioavailability of the RBD and directionally displayed the neutralizing epitopes, thereby significantly enhancing humoral and cellular immunity. Furthermore, the required dose of antigen and alum adjuvant was greatly reduced, which improved the safety and accessibility of the protein subunit vaccine. On this basis, the wide applicability of this novel strategy to a series of representative pathogen antigens such as SARS-RBD, MERS-RBD, Mpox-M1, MenB-fHbp, and Tularemia-Tul4 was further confirmed. Charge modification of antigens provides a straightforward approach for antigenicity optimization of alum-adjuvanted vaccines, which has great potential to be adopted as a global defense against infectious diseases.

On 20 July 2021, an extreme rainstorm battered Zhengzhou in China’s Henan Province, killing 302 people, including 14 individuals who drowned in a subway tunnel and 6 who drowned in a road tunnel. As the global climate warms, extreme weather events similar to the Zhengzhou flood will become more frequent, with increasingly catastrophic consequences for society. Taking a case study-based approach by focusing on the record-breaking Zhengzhou flood, this paper examines the governance capacity of inland cities in North China for managing extreme precipitation and flooding events from the perspective of the flood risk management process. Based on in-depth case analysis, our paper hypothesizes that inland cities in North China still have low risk perceptions of extreme weather events, which was manifested in insufficient pre-disaster preparation and prevention, poor risk communication, and slow emergency response. Accordingly, it is recommended that inland cities update their risk perceptions of extreme rainfall and flooding events, which are no longer low-probability, high-impact “black swans”, but turning into high-probability, high-impact “gray rhinos.” In particular, cities must make sufficient preparation for extreme weather events by revising contingency plans and strengthening their implementation, improving risk communication of meteorological warnings, and synchronizing emergency response with meteorological warnings.

In this paper, we fabricate a pair of fiber Bragg gratings (FBGs) in large mode area double cladding fiber (LMA-DCF, core/inner cladding diameter: 20/400 μm) by visible (515 nm) femtosecond laser and phase mask for the first time to the best of our knowledge. Then this pair of FBGs are utilized to construct a high power fiber oscillator operated near 1080 nm. The maximum output laser power is more than 3.2 kW with a slope efficiency of ∼77.9%, and the beam quality factor M2 is about 1.28. The FBGs are simply fixed on water-cooling plate without any special package, and the temperature of the FBGs is about 40 °C at the maximum output power. Our research work confirms the reliability of visible femtosecond laser in fabrication of FBGs intended to be applied in high power fiber oscillators.

Abstract Introduction Recent studies have demonstrated the presence of a circulating microbiome in the blood of healthy subjects and chronic inflammatory patients. However, our knowledge regarding the blood microbiome and its potential roles in surgical patients remains very limited. The objective of this study was to determine the blood microbial landscape in surgical patients and to explore its potential associations with postoperative sepsis. Materials and Methods 2825 patients who underwent surgical treatments were screened for enrollment and 204 cases were recruited in this study. The patients were sub‐grouped into noninfected, infected, sepsis, and septic shock according to postoperative clinical manifestations. A total of 222 blood samples were obtained for neutrophil isolation, DNA extraction and high‐throughput sequencing, quantitative proteomics analysis, and flow cytometric analyses. Results Blood and neutrophils in surgical patients and healthy controls contained highly diverse microbiomes, mainly comprising Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. The majority (80.7%–91.5%) of the microbiomes were composed of gut‐associated bacteria. The microbiomes in septic patients were significantly distinct from those of healthy controls, and marked differences in microbiome composition were observed between sepsis and septic shock groups. Several specific bacterial genera, including Flavobacterium, Agrococcus, Polynucleobacter, and Acidovorax, could distinguish patients with septic shock from those with sepsis, with higher area under curve values. Moreover, Agrococcus, Polynucleobacter, and Acidovorax were positively associated with the sequential (sepsis‐related) organ failure assessment scores and/or acute physiology and chronic health examination scores in septic shock patients. The proteins involved in bactericidal activities of neutrophils were downregulated in septic patients. Conclusions We present evidence identifying significant changes of blood and neutrophil‐specific microbiomes across various stages of sepsis, which might be associated with the progression of sepsis after surgical treatments. Several certain bacterial genera in blood microbiome could have potential as microbial markers for early detection of sepsis.

Presently, the full implementation of the negotiations and collaborations under the Paris Agreement faces new key problems and severe challenges. These problems and challenges include the following: how to honor the principle of “common but differentiated responsibilities” to facilitate a comprehensive, balanced, and effective implementation of the key elements of the Paris Agreement, such as adaptation, mitigation, finance, technology, capacity building, and transparency; how to uphold and maintain the status of China and other emerging countries as developing countries in light of the requirements of the United Nations Framework Convention on Climate Change and the historical responsibilities of these countries; and how to assess the goal of limiting the global temperature increase to 1.5°C and what constitutes an equitable carbon mitigation pathway for different types of countries. Developed countries and developing countries have drastically diverging views on carbon border adjustment measures for trade with developing countries proposed by several developed countries such as the European Union. Developed countries have demonstrated obvious intentions and actions designed to weaken and neglect the principle of “common but differentiated responsibilities”, to impose mitigation pressure on developing countries, to shift the responsibilities for emissions onto others, and to pass on the costs of mitigation. The maneuvering among different types of countries and interest groups has become increasingly intense. In response, China must maintain its strategic focus, adhere to the goals and principles established by the Paris Agreement, stick to its strategic positioning as a developing country, solidify strategic support from the developing world, and safeguard the legitimate rights and interests of developing countries. China played a conducive role in facilitating the Paris Agreement and has become an active participant, contributor, and leader in global climate governance. China must continue to follow Xi Jinping Thought on Socialism with Chinese Characteristics for a New Era and its conception of ecological civilization and the concept of building a community of common destiny, to actively lead the cooperation process in the construction of a global climate governance system characterized by equity, justice, and win–win collaborations, and to promote compliance with the Paris Agreement. At the same time, China should accelerate the green, low-carbon, circular transformation of its economy; accelerate the coordinated governance of the economy, environment, and climate change; and formulate and implement a long-term low-carbon development strategy. By the middle of the 21st century, while achieving the goal of building a great modern socialist country, China can also achieve a deep decarbonization development path that is in line with the goal of limiting the global temperature increase to well below 2 °C and pursuing efforts to limit the increase to 1.5°C.

Evolution of accretion disk and corona during outbursts in black hole binary systems is still unclear. Here, the authors show spectral analysis of MAXI J1820+070 and propose a scenario of a dynamical corona to explain the evolution of the reflection fraction observed by Insight-HXMT.

As the world's biggest carbon dioxide (CO2) emitter and the largest developing country, China faces daunting challenges to peak its emissions before 2030 and achieve carbon neutrality within 40 years. This study fully considered the carbon-neutrality goal and the temperature rise constraints required by the Paris Agreement, by developing six long-term development scenarios, and conducting a quantitative evaluation on the carbon emissions pathways, energy transformation, technology, policy and investment demand for each scenario. This study combined both bottom-up and top-down methodologies, including simulations and analyses of energy consumption of end-use and power sectors (bottom-up), as well as scenario analysis, investment demand and technology evaluation at the macro level (top-down). This study demonstrates that achieving carbon neutrality before 2060 translates to significant efforts and overwhelming challenges for China. To comply with the target, a high rate of an average annual reduction of CO2 emissions by 9.3% from 2030 to 2050 is a necessity, which requires a huge investment demand. For example, in the 1.5 °C scenario, an investment in energy infrastructure alone equivalent to 2.6% of that year's GDP will be necessary. The technological pathway towards carbon neutrality will rely highly on both conventional emission reduction technologies and breakthrough technologies. China needs to balance a long-term development strategy of lower greenhouse gas emissions that meets both the Paris Agreement and the long-term goals for domestic economic and social development, with a phased implementation for both its five-year and long-term plans.

Hopf algebras, as a crucial generalization of groups, have a very symmetric structure and have been playing a prominent role in mathematical physics. In this paper, let H be a dual quasi-Hopf algebra which is a more general Hopf algebra structure. A. Balan firstly introduced the notion of right-right Yetter-Drinfeld modules over H and studied its Galois extension. As a continuation, the aim of this paper is to introduce more properties of Yetter-Drinfeld modules. First, we will describe all the other three kinds of Yetter-Drinfeld modules over H, and the monoidal and braided structure of the categories of Yetter-Drinfeld modules explicitly. Furthermore, we will prove that the category HHYDfd of finite dimensional left-left Yetter-Drinfeld modules is rigid. Then we will compute explicitly the canonical isomorphisms in HHYDfd. Finally, as an application, we will rewrite the isomorphisms in the case of coquasitriangular dual quasi-Hopf algebra.

Stimulated Raman scattering (SRS) is a major limiting factor for better performance of high-power fiber lasers. Several spectral filtering methods have been used for Raman suppression, among which long period fiber grating (LPFG) is relatively simple and effective due to its all-fiber structure and broadband rejection properties. Here, a broadband, low insertion loss and low thermal effect LPFG is easily fabricated using CO2 laser by galvanometer scanning, then is used for SRS suppression within a high-power fiber oscillator for the first time. Results show that a maximum SRS suppression ratio of ~16 dB was achieved and the extractable Raman-free output power was increased by about 13% with the insertion of LPFG. This work has demonstrated a potentially applicable method for Raman suppression in high-power fiber oscillators.

Based on CFD analysis technology, this paper studies the cavitation performance of an LNG submerged pump and the pressure pulsation characteristics under cavitation excitation. The variation laws of the waveform, amplitude and frequency of the pressure pulsation in the impeller of the LNG submerged pump under different flow rates and NPSHa are also analysed. By calculating the root mean square of the pressure coefficient of the low-frequency pulsation, the influence of the aggravation process of cavitation on the low-frequency pulsation in the LNG submerged pump is quantitatively analysed, and the characteristics of the pressure pulsation in the LNG submerged pump under the cavitation condition are revealed. The results show that with the increase in flow rate, the pressure pulsation in the impeller becomes stronger, periodically, and the amplitude decreases. The influence of cavitation on the pressure pulsation in the primary impeller is greater than that in the secondary impeller. When critical cavitation occurs, the low-frequency signal amplitude of pressure pulsation in the primary impeller increases and exceeds the blade frequency, becoming the main frequency.

We report a high power, narrow linewidth fiber laser based on oscillator one-stage power amplification configuration. A fiber oscillator with a center wavelength of 1080 nm is used as the seed, which is based on a high reflection fiber Bragg grating (FBG) and an output coupling FBG of narrow reflection bandwidth. The amplifier stage adopted counter pumping. By optimizing the seed and amplifier properties, an output laser power of 2276 W was obtained with a slope efficiency of 80.3%, a 3 dB linewidth of 0.54 nm and a signal to Raman ratio of 32 dB, however, the transverse mode instability (TMI) began to occur. For further increasing the laser power, a high-power chirped and tilted FBG (CTFBG) was inserted between the backward combiner and the output passive fiber, experimental results showed that both the threshold of Stimulated Raman scattering (SRS) and TMI increased. The maximum laser power was improved to 2576 W with a signal to Raman ratio of 42 dB, a slope efficiency of 77.1%, and a 3 dB linewidth of 0.87 nm. No TMI was observed and the beam quality factor M2 maintained about 1.6. This work could provide a useful reference for obtaining narrow-linewidth high-power fiber lasers with high signal to Raman ratio.

Line-by-line direct writing by femtosecond laser has been proved to be a simple and effective method for the fabrication of low-loss fiber Bragg gratings (FBGs), and is more flexible compared with the traditional ultraviolet exposure method. In this paper, the line-position-dependent characteristics of cladding modes coupling in line-by-line FBGs have been studied, to the best of our knowledge, for the first time. Both theoretical and experimental results show that off-center inscribing could compress the bandwidth of the Bragg resonance and excite more abundant cladding mode coupling, in which the core-guided fundamental mode would couple to the cladding-guided LP0n and LP1n simultaneously. By aligning the line positions across the core region, the first apodized line-by-line FBG was achieved. This work enriches the theories of line-by-line FBGs and provides an inscription guidance to meet different application requirements.

Chirped and tilted fiber Bragg gratings (CTFBGs) have attracted a lot of attention in stimulated Raman scattering (SRS) suppression of high-power fiber lasers. However, the laser power handling capacity seriously limits their applications. In this paper, by optimizing the inscription parameters and post-processing strategy, we fabricate a large-mode-area double-cladding CTFBG with a thermal slope of ~0.015 °C/W due to the low insertion loss of about 0.15 dB, which make it possible for direct kilowatt-level application. A 2 kW-level fiber laser oscillator is employed to test the CTFBG, and a series of experiments have been carried out to compare the effect of SRS mitigation in high-power fiber laser long-distance delivery. In addition, the influence of CTFBGs on laser beam quality is studied for the first time. Experimental results indicated that the CTFBG could effectively mitigate SRS and has no obvious influence on laser beam quality. This work opens a new opportunity for further power scaling and the delivery of high-power fiber lasers over longer distances.

Fabry-Perot cavity (FPC) based on Fiber Bragg gratings (FBGs) is an excellent candidate for fiber sensing and high-precision measurement. The advancement of the femtosecond laser micromachining technique provides more choices for the fabrication of FBGs-based FPCs. In this paper, we fabricate miniature FBGs-based FPCs, using the femtosecond laser line-by-line scanning writing technique for the first time. By this method, the FBGs can be limited to a specific area in the fiber core region. The grating length, position, and the distance between two successive FBGs can be conveniently controlled to achieve the desired transmission spectrum. For future applications in sensing, the temperature and strain responses of the fabricated FBGs-based FPCs were studied experimentally. This work provides a meaningful guidance for the fabrication and application of miniature FPCs based on FBGs.

In this paper, we studied the basic characteristics of tilted fiber Bragg gratings (TFBGs), inscribed line-by-line. Experimental results showed that if the TFBGs were located within different planes parallel to the fiber axis, the spectra performed differently. For 2°TFBG, if it was located near the central plane, the Bragg resonance was stronger than ghost mode resonance, and the order reversed if it was located near the boundary between core and cladding. As the tilted angle increased, the range of cladding mode resonance increased. When the tilted angle was larger than 12°, the birefringence effect was observed. Based on the birefringence phenomenon, torsion characteristics were experimentally studied; the sensitivity was about 0.025 dB/degree in the linear variation range. The harmonic order of TFBGs also affected the transmission spectrum. Leaky mode resonance was observed in the 8th order TFBG, and torsion (or polarization) influenced the spectrum of the 8th order TFBG. Our research represented the theory of line-by-line inscribed TFBGs and provided an inscription guidance for TFBGs.

We study here the spectral characteristics of square-wave-modulated type II long-period fiber gratings (LPFGs) inscribed by a femtosecond laser. Both theoretical and experimental results indicate that higher-order harmonics refractive index (RI) modulation commonly exists together with the fundamental harmonic RI modulation in such LPFGs, and the duty cycle of a square wave has a great influence on the number and amplitudes of higher-order harmonics. A linear increase in the duty cycle in a series of square wave pulses will induce another LPFG with a minor difference in periods, which is useful for expanding the bandwidth of LPFGs. We also propose a method to reduce insertion loss by fabricating type II LPFGs without higher-order harmonic resonances. This work intensifies our comprehension of type II fiber gratings with which novel optical fiber sensors can be fabricated.

Background/Aims: Intestinal transplantation is an effective treatment for end-stage bowel failure; however, graft rejection and the toxicity associated with non-specific immunosuppression are major limitations of this procedure. Studies have shown that mixed chimerism can produce post-transplantation immune tolerance. Here, we demonstrate that in rat intestinal transplantation, PU.1-silenced dendritic cells (DCs) plus bone marrow (BM) cell transfusion results in mixed chimerism, and we investigate the mechanisms responsible for the effects of mixed chimerism rejection. Methods: In a model of intestinal transplantation, male Brown Norway rats were the donors, and female Lewis rats were the recipients that were randomly divided into 4 groups: control, BM, BM-imDCs and BM-PU.1. The dynamic changes in graft morphology, rejection scoring and serum concentrations of Th1/Th2-related cytokines were investigated on postoperative days 0, 7, 14, 21, and 30. Results: The BM-PU.1 group had better graft health, milder pathologic injuries, and lower rejection grades compared with the other groups. The rates of mixed chimerism were significantly highest in the BM-PU.1 group and correlated with decreases in serum IL-2 and increases in serum IL-10. Conclusion: Transfusion of PU.1-silenced DCs and BM cells induces stable mixed chimerism and has the potential to reduce pathologic injuries via a pro-Th2 shift in the Th1/Th2 balance.

Er3+-sensitized upconversion nanoparticles (UCNPs) have attracted great attention due to their tunable upconversion (UC) emissions, low cytotoxicity, high resistance to photobleaching and especially multiple effective excitation wavelengths. However, detailed energy conversion between Er3+ and Tm3+ ions in Y2O3 UCNPs is still a problem, especially under multi-wavelength and variable pulse width excitation. In this work, we successfully fabricated a series of Er3+-sensitized Y2O3 nanocrystals by a spray flame synthesis method with a production rate of 40.5 g h−1. The as-prepared UCNPs are a pure cubic phase with a mean size of 14 nm. Excited by both 980 and 808 nm lasers, the tunable upconversion luminescence (UCL) from Er3+ ions was achieved by increasing the Er3+ doping concentration, co-doping Tm3+ ions and extending excitation pulse-width. The investigations of the lifetimes and the laser power dependence of UC emissions further support the proposed mechanism, which provides guidance for achieving effective color control in anticounterfeiting and multiplexed labeling applications. In addition, the red UC emission at about 5 mm beneath the tissue surface was observed in an ex vivo imaging experiment under the excitation of 808 nm laser, indicating that the Y2O3:Er3+/Tm3+ UCNPs have great prospects in further biological applications.

Infectious complications are a leading cause of death for patients with severe acute pancreatitis (SAP). Yet, our knowledge about details of the blood microbial landscape in SAP patients remains limited. Recently, some studies have reported that the peripheral circulation harbors a diverse bacterial community in healthy and septic subjects. The objective of this study was to examine the presence of the blood bacterial microbiome in SAP patients and its potential role in the development of infectious complications. Here we conducted a prospective observational study on a cohort of 50 SAP patients and 12 healthy subjects to profile the bacterial composition in the blood. The patients were subgrouped into uninfected (n = 17), infected (n = 16), and septic (n = 17) cases. Applying 16S rDNA-based next-generation sequencing technique, we investigated blood and neutrophil-associated microbiomes in SAP patients, and assessed their connections with immunological alterations. Based on the sequencing data, a diverse bacterial microbiota was found in peripheral blood and neutrophils from the healthy and SAP subjects. As compared to healthy controls, the blood and neutrophil-associated microbiomes in the patients were significantly altered, with an expansion in Bacteroidetes and Firmicutes as well as a decrease in Actinobacteria. Variations in the microbiome composition in patients were associated with immunological disorders, including altered lymphocyte subgroups, elevated levels of serum cytokines and altered proteomic profiles of neutrophils. However, no significant compositional difference was observed between the patient subgroups, implying that the microbiota alterations might not be linked to presence/absence of infectious complications in SAP. Together, we present an initial description of the blood and neutrophil-associated bacterial profiles in SAP patients, offering novel evidence for the existence of the blood microbiome. Identification of the blood microbiome provides novel insights into characteristics and diagnostics of bacteremia in the patients. Further study is required to assess the possible implications of the blood microbiome in health and diseases.

TFDP3, also be known as HCA661, was one of the cancer-testis antigens, which only expressed in human tissues. The recent researches about TFDP3 mostly focused on its ability to control the drug resistance and apoptosis of tumor cells. However, the role of TFDP3 in the progress of the cell cycle is rarely involved. In this study, we examined the expression of TFDP3 in human liver tissues firstly. After that, we detect the expression of TFDP3 at the RNA level and protein level in L-02 cell line and HepG2 cell line, and the location of TFDP3 was defined by immunofluorescence technique. Furthermore, we synchronized the cells to G1 phase, S phase and G2 phase, and arrested cell mitosis. The localization of TFDP3 and co-localization with E2F1 molecules in different phases of hepatocyte lines. Finally, TFDP3 gene knockout was performed on L-02 and HepG2 cell lines, and detected the new cell cycles by flow cytometry. The result showed that the expression of TFDP3 molecule is negative in normal liver tissue, but positive in immortalized human hepatocyte cell line, and the expression level is lower than in hepatocellular carcinoma cell line. The expression level of TFDP3 was in the dynamic change of L-02 and HepG2 cell lines, and was related to the phase transition. TFDP3 can bind to E2F1 molecule to form E2F/TFDP3 complex; and the localizations of TFDP3 and E2F1 molecules and the co-localization were different in different phases of cell cycle in the nucleus and cytoplasm, which indicated that the E2F/TFDP3 complex involved in the process of regulating the cell cycle. By knocking down the TFDP3 expression level in L-02 and HepG2 cell lines, the cell cycle would be arrested in S phase, which confirmed that TFDP3 can be a potential target for tumor therapy.