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Abstract Background Grilled Nux Vomica (GNV) is a promising traditional Chinese medicine to treat myasthenia gravis (MG), but its effects and mechanisms need further exploration. Methods Experimental autoimmune MG (EAMG) model was established by muscle-specific kinase (MuSK) induction on C57BL/6 J mice. Mice were treated with GNV and/or ruxolitinib (JAK2 inhibitor) or AG490 (STAT3 inhibitor) for 30 days via gavage after modeling and randomized into 7 groups: control, model, low-dose GNV, middle-dose GNV, high-dose GNV, GNV + ruxolitinib, GNV + AG490. Body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity (agrin and acetylcholine receptor [AChR] levels), inflammatory factors (IL-2 and IL-6), and the activation of the JAK2/STAT3 pathway were measured and compared between groups. Results GNV significantly improved body weight and muscle strength, as well as reduced clinical scores, MuSK levels, and inflammatory markers (IL-2 and IL-6) levels compared with untreated EAMG mice. GNV also protected the neuromuscular junction and increased agrin and AChR co-expression in a dose-dependent manner. In addition, GNV attenuated the levels of p-JAK2 and p-STAT3, which are aberrantly upregulated in EAMG mice. After co-treatment with ruxolitinib or AG490, the effect of GNV on body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity, levels of inflammatory factors, and JAK2/STAT3 pathway was further amplified in EAMG mice. Conclusions GNV improves MG by inhibiting the JAK2/STAT3 pathway, which might be an effective therapeutic strategy for MG.

This paper proposed a new space-air-ground integrated network caching method, that was, cluster based content caching method.Based on the space-air-ground integrated network architecture, this method used the extracted content features to predict the popularity and used it for cache replacement decision.Content popularity prediction was realized based on dynamic clustering algorithm.This method could effectively reduce the pressure on the ground backbone network and further improve the quality of user experience.It evaluated the performance of our method using the open Douban movie review dataset.This dataset could be used to simulate user requests.Experimental simulation results showed the feasibility and effectiveness of the method.

Abstract B- and T-lymphocyte attenuator (BTLA) levels are increased in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This condition is characterized by susceptibility to infection and T-cell immune exhaustion. However, whether BTLA can induce T-cell immune exhaustion and increase the risk of infection remains unclear. Here, we report that BTLA levels are significantly increased in the circulating and intrahepatic CD4+ T cells from patients with HBV-ACLF, and are positively correlated with disease severity, prognosis, and infection complications. BTLA levels were upregulated by the IL-6 and TNF signaling pathways. Antibody crosslinking of BTLA activated the PI3K-Akt pathway to inhibit the activation, proliferation, and cytokine production of CD4+ T cells while promoting their apoptosis. In contrast, BTLA knockdown promoted their activation and proliferation. BTLA-/- ACLF mice exhibited increased cytokine secretion, and reduced mortality and bacterial burden. The administration of a neutralizing anti-BTLA antibody reduced Klebsiella pneumoniae load and mortality in mice with ACLF. These data may help elucidate HBV-ACLF pathogenesis and aid in identifying novel drug targets.

Extrusion is a crucial food processing technique that involves mixing, heating, shearing, molding, and other operations to modify the structures and properties of food components. As the primary energy source material, the extrusion process induces significant physical and chemical changes in starch that impact the quality of final products. This review paper discusses novel technologies for starch extrusion and their influence on the physical and chemical properties of starch-based foods, such as gelatinization and retrogradation properties, structural characteristics, and digestion properties. Additionally, it examines the application of extrusion in starch processing and the interactions between starch and other food components during extrusion. This information sheds light on the structural and property alterations that occur during the extrusion process to create high-quality starch-based foods.

The demand for food-grade β-mannanases, ideal for high-temperature baking, is increasing. Using the Komagataella phaffii (P. pastoris) expression system for β-mannanase production, this study aimed to enhance purification methods. We evaluated better conditions for production and purification of β-mannanase (PpRmMan134A) from recombinant P. pastoris X-33, focusing on a higher purity and reducing the production of endogenous secretory proteins in fermentation. By adjusting carbon and nitrogen sources, culture time, and temperature, we controlled cell growth to reduce the production of endogenous secretory proteins. The better-evaluated conditions involved culturing recombinant P. pastoris in 70 mL buffered glycerol complex medium for 24 h at 30 °C, then in modified buffered methanol-complex medium with 0.91% (w/v) methanol, 0.56% (w/v) sorbitol, and 0.48% (w/v) mannitol for another 24 h, which improved the PpRmMan134A yield and reduced endogenous secretory proteins, shortening the fermentation time by 72 h. An affordable purification method using ultrafiltration and salt-out precipitation was utilized. PpRmMan134A showed thermostability up to 100 °C and effectively degraded locust bean gum into smaller fragments, mainly producing mannotriose. In conclusion, with its enhanced purity due to reduced levels of endogenous secretory proteins, purified PpRmMan134A emerges as a promising enzyme for high-temperature baking applications.

Abstract. The Omicron variants have continued to cause severe acute respiratory syndrome coronavirus 2 infections. To better understand the anti-viral effects of vaccination on host-virus interactions during the outbreak of BA.2.2 Omicron, we conducted RNA-seq transcriptome analysis on nasopharyngeal swabs from COVID-19 patients in Shanghai. This study was performed on selected cases from unvaccinated, fully vaccinated, and booster groups with the same founder virus infection background. We observed predominant immune cell chemotaxis and interleukin-1 production, as well as mucosal keratinization and epidermis development, in unvaccinated patients. In contrast, fully vaccinated subjects exhibited an obvious T-cell activation in the local immune response, whereas B-cell activation was higher in booster-vaccinated cases. In conclusion, our findings suggest that full or booster vaccination provides better adaptive immunity and relieve inflammation at the nasopharyngeal site, thereby reducing the risk of cytokine storm during breakthrough infection.

The efficacy of many edible bioactive agents is limited by their low water dispersibility and chemical instability in foods, as well as by their poor bioaccessibility, low absorption, and metabolism within the human gastrointestinal tract. Whey proteins are amphiphilic molecules that can be used to construct a variety of edible carrier systems that can improve the performance of bioactive ingredients. These carrier systems are being used by the food and biomedical industries to encapsulate, protect, and deliver a variety of bioactive agents. In this article, we begin by providing an overview of the molecular and functional characteristics of whey proteins, and then discuss their interactions with various kinds of bioactive agents. The ability of whey proteins to be used as building blocks to assemble different kinds of carrier systems is then discussed, including nanoparticles, hydrogels, oleogels, bigels, nanofibers, nanotubes, and nanoemulsions. Moreover, applications of these carrier systems are highlighted. Different kinds of whey protein-based carriers can be used to encapsulate, protect, and deliver bioactive agents. Each kind of carrier has its own characteristics, which make them suitable for different application needs in foods and other products. Previous studies suggest that whey protein-based carriers are particularly suitable for protecting chemically labile bioactive agents and for prolonging their release profiles. In the future, it is likely that the applications of whey protein-based carriers in the food and pharmaceutical fields will expand.

Abstract In this study, composite nanoparticles consisting of zein and hydroxypropyl beta-cyclodextrin were prepared using a combined antisolvent co-precipitation/electrostatic interaction method. The effects of calcium ion concentration on the stability of the composite nanoparticles containing both curcumin and quercetin were investigated. Moreover, the stability and bioactivity of the quercetin and curcumin were characterized before and after encapsulation. Fluorescence spectroscopy, Fourier Transform infrared spectroscopy, and X-ray diffraction analyses indicated that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were the main driving forces for the formation of the composite nanoparticles. The addition of calcium ions promoted crosslinking of the proteins and affected the stability of the protein–cyclodextrin composite particles through electrostatic screening and binding effects. The addition of calcium ions to the composite particles improved the encapsulation efficiency, antioxidant activity, and stability of the curcumin and quercetin. However, there was an optimum calcium ion concentration (2.0 mM) that provided the best encapsulation and protective effects on the nutraceuticals. The calcium crosslinked composite particles were shown to maintain good stability under different pH and simulated gastrointestinal digestion conditions. These results suggest that zein–cyclodextrin composite nanoparticles may be useful plant-based colloidal delivery systems for hydrophobic bio-active agents.

Abstract Nisin is a natural bacteriocin that exhibits good antibacterial activity against Gram-positive bacteria. It has good solubility, stability, and activity under acidic conditions, but it becomes less soluble, stable, and active when the solution pH exceeds 6.0, which severely restricted the industrial application range of nisin as antibacterial agent. In this study, we investigated the potential of complexing nisin with a cyclodextrin carboxylate, succinic acid-β-cyclodextrin (SACD), to overcome the disadvantages. Strong hydrogen bonding was shown between the nisin and SACD, promoting the formation of nisin-SACD complexes. These complexes exhibited good solubility under neutral and alkaline conditions, and good stability after being held at high pH values during processing with high-steam sterilization. Moreover, the nisin-SACD complexes displayed significantly improved antibacterial activity against model Gram-positive bacteria (S. aureus). This study shows that complexation can improve the efficacy of nisin under neutral and alkaline situations, which may greatly broaden its application range in food, medical, and other industries.

In this paper, the mechanoelectrochemical effect on the electrochemical corrosion of 316 L austenitic stainless steel was investigated by theoretical, experimental and simulated methods. The modified piecewise formula φa,eq=φa,eq0−ΔPmVmzF−TRzFln(KN0εp+1) for calculating the strain on anode equilibrium potential of austenitic stainless steel was proposed. It is demonstrated that the corrosion current increases from 8.03×10−6A⋅cm−2 to 28.38×10−6A⋅cm−2 within 20% strain, especially within 10%, which is in better agreement with the experimental results. This modification not only made the physical meaning of parameters clearer, simplified the formula, but also made the calculation results more accurate. Moreover, the localized galvanic corrosion caused by non-uniform deformation had been verified by finite element model. The results revealed that the non-uniform strain at the initial stage of strain (εp

Abstract Background Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. Methods We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. Results During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. Conclusion The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.

ABSTRACT Metagenomic next-generation sequencing (mNGS) has been a lack of method for pathogen quantitation. We explored the suitable concentration of T1 phage [internal control (IC)phage], Thermus thermophilus (ICT.T), and artificial DNA sequence (ICDNA) as mNGS ICs for pathogen quantitation and compared the quantitation efficiency among them. We prepared the simulated cerebrospinal fluid (CSF) samples composed of a pathogen cocktail, containing Staphylococcus aureus, Escherichia coli, Komagataella pastoris, and human cells to test the accuracy, linearity, and interference of IC quantitation. We also collected 15 clinical CSF conducting both mNGS and droplet digital PCR (ddPCR) to further verify the quantification efficacy of IC. In accuracy, the mNGS quantification of pathogen was more precise when the IC was 103 and 104 CFU/mL Thermus thermophilus or 103 and 104 PFU/mL T1 phage with the CV% of pathogens quantification most below 15%. The DNA sequence’ quantification was less accurate with all the CV% of pathogen quantitation above 15%. In linearity, compared to DNA sequence (all R 2 0.9). In interference, the mNGS quantification was affected obviously by human cell concentrations when the IC was DNA sequence (P < 0.0001), and the quantification was not interfered when the IC was the 103 CFU/mL Thermus thermophilus or 104 PFU/mL T1 phage. Furthermore, we revealed the mNGS quantitation was highly consistent with ddPCR in clinical CSF according to the linear regression (R 2 = 0.9646, P < 0.0001, k = 0.9362) and Bland-Altman (the bias of average difference is 4.033, with the 95% confidence interval from − 24.61 to 32.68). Thermus thermophilus and T1 phages are comparable as mNGS IC in pathogen quantitation and are both superior than artificial DNA sequences. In total, 1,000-CFU/mL Thermus thermophilus as mNGS IC may allow us to reflect directly the variation of pathogens in central nervous system infection patients. IMPORTANCE Metagenomic next-generation sequencing (mNGS) has been used broadly for pathogens detection of infectious diseases. However, there is a lack of method for the absolute quantitation of pathogens by mNGS. We compared the quantitative efficiency of three mNGS internal controls (ICs) Thermus thermophilus, T1 phages, and artificial DNA sequence and developed the most applicable strategies for pathogen quantitation via mNGS in central nervous system infection. The IC application strategy we developed will enable mNGS analysis to assess the pathogen load simultaneously with the detection of pathogens, which should provide critical information for quick decision-making of treatment as well as clinical prognosis.

Background: Omicron had swept the mainland China between December 2022 and January 2023, while SARS-CoV-2 still continued to evolve. To fully prepare for the next wave, it’s urgent to evaluate the humoral immune response post BA.5/BF.7 breakthrough infection against predominant sub-lineages among existing vaccination strategies and the elders. Method: This study enrolled a longitudinal young-adult cohort from 2/3-dose vaccination to 1 month after breakthrough infection, and an elder cohort at 1 month after breakthrough infection. Seral samples were collected and tested for humoral immune response to SARS-CoV-2 subvariants including WT, BA.2, BA.5, BF.7, BQ.1.1, CH.1.1, XBB.1.5. Results: BA.5/BF.7 breakthrough infection induced higher neutralization activity than solely vaccination in all SARS-CoV-2 strains, while the latest Omicron subvariants, BQ.1.1, CH.1.1, XBB.1.5, exhibited the strongest neutralization evasion ability. There was a negative correlation between age and humoral immune response in WT, BA.5, BQ.1.1, and XBB.1.5. Compared to non-vaccination groups, breakthrough infection in two-dose vaccination groups had significantly higher neutralizing antibody against WT, BA.2, BA.5, BF.7 but not to BQ.1.1, CH.1.1, XBB.1.5 while booster dose against the prototype prior-breakthrough would not further significantly enhance individual’s humoral responses against the latest Omicron subvariants. Conclusions: Newer variants manifest increasing immune evasion from neutralization and repeated prototype-based booster vaccines may not further enhance neutralizing antibody against emerging new variants. Older adults have lower levels of neutralizing antibody. Future vaccination strategies should aim to enhance effective neutralization to contemporary variants.

Abstract Background Childhood inadequate eating behaviors contribute to the epidemic of obesity. Previous research suggests that parental feeding practices are partially associated with development of eating behaviors among children, but the results are inconsistent. The present study was to investigate whether parental feeding practices were associated with eating behaviors and food preferences among Chinese children. Methods A cross-sectional study was conducted to collect data from 242 children (ages 7–12) in six-primary schools in Shanghai, China. A series of questionnaires including parental feeding practices and children’s eating behaviors have been validated, and were completed by one of parent who has responded for child’s daily diet and living. In addition, researchers instructed children to complete the questionnaire of food preference. After adjustment for children’s age, sex and BMI status, as well as parental education and family income, the linear regression analysis was used to evaluate relationships of parental feeding practices with children’s eating behaviors and food preferences. Results Parents with boys had higher level of control overeating practice than those with girls. Mothers who responded to child’s daily diet and living and completed feeding practices questionnaire used a greater level of emotional feeding practices than fathers. Boys had higher levels of food responsiveness, emotional overeating, enjoyment of food and desire to drink than girls. Boys had different preferences for meat, processed meat products, fast foods, dairy foods, eggs, and snacks and starchy staples & beans from girls. In addition, scores of instrumental feeding practice and preference for meat significantly differed among children with different weight status. Furthermore, parental emotional feeding practice was positively associated with children’s emotional undereating (β 0.54, 95% CI 0.16 to 0.92). There were also positive associations of parental encouragement to eat with children’s preference for the processed meat (β 0.43, 95% CI 0.08 to 0.77). Moreover, instrumental feeding practice was negatively associated with children’s fish liking (β -0.47, 95% CI -0.94 to -0.01). Conclusion The current findings support associations of emotional feeding practice with some children’s emotional undereating, as well as parental encouragement to eat and instrumental feeding practice related to preference for processed meat and fish, respectively. Further studies should continue to ascertain these associations using longitudinal designs, and to evaluate efficacy of parental feeding practices impacting developments of healthy eating behaviors and preferences for healthy foods among children by interventional studies.

Nonvolatile compact on-chip optical filters with a tunable spectral response are required in low-power optical communication systems and applications. By capping phase change materials (PCMs) films on a phase-shifted Bragg grating (PSBG), the key parameters of a filter such as center wavelength and extinction ratio can be tuned simultaneously for filtering or processing purposes. A 9 nm wavelength shift, and amplitude modulations of 16.1 dB in the transmission channel and 42.5 dB in the reflection channel while keeping the center wavelength unchanged are achieved in this filter at 1550 nm. Moreover, the device has a compact size of 500 nm × 31.9 $\mu$m and an insertion loss as low as -0.76 dB, making it ideal for large-scale integration. The advent of such compact, reconfigurable, nonvolatile optical filters opens up new avenues for next-generation low-power general-purpose photonic integrated circuits (PICs) and has potential applications in wavelength division multiplexing (WDM) systems, spectral shaping, and on-chip signal processors.

The emerging new VOC B.1.1.529 (Omicron) variant has raised serious concerns due to multiple mutations, reported significant immune escape, and unprecedented rapid spreading speed. Currently, studies describing the neutralization ability of different homologous and heterologous booster vaccination against Omicron are still lacking. In this study, we explored the immunogenicity of COVID-19 breakthrough patients, BBIBP-CorV homologous booster group and BBIBP-CorV/ZF2001 heterologous booster group against SARS-CoV-2 pseudotypes corresponding to the prototype, Beta, Delta, and the emergent Omicron variant. Notably, at 14 days post two-dose inactivated vaccines, pVNT titre increased to 67.4 GMTs against prototype, 8.85 against Beta and 35.07 against Delta, while neutralization activity against Omicron was below the lower limit of quantitation in 80% of the samples. At day 14 post BBIBP-CorV homologous booster vaccination, GMTs of pVNT significantly increased to 285.6, 215.7, 250.8, 48.73 against prototype, Beta, Delta, and Omicron, while at day 14 post ZF2001 heterologous booster vaccination, GMTs of pVNT significantly increased to 1436.00, 789.6, 1501.00, 95.86, respectively. Post booster vaccination, 100% samples showed positive neutralization activity against Omicron, albeit illustrated a significant reduction (5.86- to 14.98-fold) of pVNT against Omicron compared to prototype at 14 days after the homologous or heterologous vaccine boosters. Overall, our study demonstrates that vaccine-induced immune protection might more likely be escaped by Omicron compared to prototypes and other VOCs. After two doses of inactivated whole-virion vaccines as the “priming” shot, a third heterologous protein subunit vaccine and a homologous inactivated vaccine booster could improve neutralization against Omicron.

Breakthrough infection of SARS-CoV-2 is a serious challenge, as increased infections were documented in fully-vaccinated individuals. Recipients with poor antibody response are highly vulnerable to reinfection, whereas those with strong antibody responses achieve sterilizing immunity. Thus far, biomarkers associated with levels of vaccine-elicited antibody response are still lacking. Here, we studied the antibody response of age- and gender-controlled healthy cohort, who received inactivated SARS-CoV-2 vaccines and profiled the B cell receptor repertoires in longitudinally consecutive samples. Upon vaccination, all vaccinated individuals displayed a convergent antibody response with shared common antibody clones and public neutralizing antibodies. Strikingly, poor vaccine-responders are distinguishable from strong vaccine-responders by a biased V-usage before vaccination and IgG to IgM mRNA ratio. These findings reveal molecular signatures associated with the different levels of vaccine-induced antibody response, which could be further developed into biomarkers for the design of vaccination strategies.

A COVID-19 booster vaccination is being comprehensively evaluated globally due to the emerging concern of reduced protection rate of previous vaccination and circulating Variants of Concern (VOC). But the safety and immunogenicity of homologous BBIBP-CorV boosting vaccination are yet to be thoroughly evaluated. We conducted this prospective, open-label study in Huashan Hospital using a third 6.5U BBIBP-CorV administered at an interval of 4–8 months following the previous two doses in healthy adults. Safety, anti-RBD response and neutralizing titers against SARS-CoV-2 and VOCs were examined. Sixty-three and forty participants entered the booster and the control group, respectively. A significant increase in IFN-γ SFU per million PBMCs was observed on day 14 against N peptide (20 vs. 5, P

Abstract SARS-CoV-2 vaccine booster dose can induce a robust humoral immune response, however, its cellular mechanisms remain elusive. Here, we investigated the durability of antibody responses and single-cell immune profiles following booster dose immunization, longitudinally over 6 months, in recipients of a homologous BBIBP-CorV/BBIBP-CorV or a heterologous BBIBP-CorV/ZF2001 regimen. The production of neutralizing antibodies was dramatically enhanced by both booster regimens, and the antibodies could last at least six months. The heterologous booster induced a faster and more robust plasmablast response, characterized by activation of plasma cells than the homologous booster. The response was attributed to recall of memory B cells and the de novo activation of B cells. Expanded B cell clones upon booster dose vaccination could persist for months, and their B cell receptors displayed accumulated mutations. The production of antibody was positively correlated with antigen presentation by conventional dendritic cells (cDCs), which provides support for B cell maturation through activation and development of follicular helper T (Tfh) cells. The proper activation of cDC/Tfh/B cells was likely fueled by active energy metabolism, and glutaminolysis might also play a general role in promoting humoral immunity. Our study unveils the cellular mechanisms of booster-induced memory/adaptive humoral immunity and suggests potential strategies to optimize vaccine efficacy and durability in future iterations.

In recent years, smart wireless remote water meters have become popular, but this kind of smart water meter needs an external power supply, and every 100 to 200 installed this type of water meter, needs to set up an independent collector. This kind of water meter is expensive, and the external power supply will increase the energy consumption of the building, which is not conducive to the circuit safety of the old community. In order to reduce the burden of manual meter reading and reduce the building's ''carbon emissions''. A wireless water consumption sensing system for buildings based on machine learning and water energy collection is designed. Images are collected and recognized by visual sensors to realize the visual reading of water meter data. The system is powered by a 12V micro water generator and transferred to lithium battery energy storage to realize the self-energy supply of the whole system. The lightweight YOLOv5 was used to implement the model training process. Then, on the premise of the small sample data set, the data set was expanded by a data enhancement method which randomly changed the image brightness and hue. Finally, the training model is deployed on MCU through the TensorFlow Lite framework to realize edge AI detection. Experiments show that the size of the lightweight YOLOv5 is reduced by 87.1% and the mAP reaches 92.3%. The system can complete the water meter wireless meter reading and realize the system self-power stably. In addition, the system can be expanded for other meter reading tasks based on visual features.

The exceptional performance of graphene has driven the advancement of its preparation techniques and applications. Laser-induced graphene (LIG), as a novel graphene preparation technique, has been applied in various fields. Graphene periodic structures created by the LIG technique exhibit superhydrophobic characteristics and can be used for deicing and anti-icing applications, which are significantly influenced by the laser parameters. The laser surface treatment process was simulated by a finite element software analysis (COMSOL Multiphysics) to optimize the scanning parameter range, and the linear array surface structure was subsequently fabricated by the LIG technique. The generation of graphene was confirmed by Raman spectroscopy and energy-dispersive X-ray spectroscopy. The periodic linear array structure was observed by scanning electron microscopy (SEM) and confocal laser imaging (CLSM). In addition, CLSM testings, contact angle measurements, and delayed icing experiments were systematically performed to investigate the effect of scanning speed on surface hydrophobicity. The results show that high-quality and uniform graphene can be achieved using the laser scanning speed of 125 mm/s. The periodic linear array structures can obviously increase the contact angle and suppress delayed icing. Furthermore, these structures have the enhanced ability of the electric heating deicing, which can reach 100 °C and 240 °C within 15 s and within 60 s under the DC voltage power supply ranging from 3 to 7 V, respectively. These results indicate that the LIG technique can be developed to provide an efficient, economical, and convenient approach for preparing graphene and that the hydrophobic surface array structure based on LIG has considerable potential for deicing and anti-icing applications.

Abstract Background The outbreak of SARS-CoV-2 at the end of 2019 sounded the alarm for early inspection on acute respiratory infection (ARI). However, diagnosis pathway of ARI has still not reached a consensus and its impact on prognosis needs to be further explored. Methods ESAR is a multicenter, open-label, randomized controlled, non-inferiority clinical trial on evaluating the diagnosis performance and its impact on prognosis of ARI between mNGS and multiplex PCR. Enrolled patients will be divided into two groups with a ratio of 1:1. Group I will be directly tested by mNGS. Group II will firstly receive multiplex PCR, then mNGS in patients with severe infection if multiplex PCR is negative or inconsistent with clinical manifestations. All patients will be followed up every 7 days for 28 days. The primary endpoint is time to initiate targeted treatment. Secondary endpoints include incidence of significant events (oxygen inhalation, mechanical ventilation, etc.), clinical remission rate, and hospitalization length. A total of 440 participants will be enrolled in both groups. Discussion ESAR compares the efficacy of different diagnostic strategies and their impact on treatment outcomes in ARI, which is of great significance to make precise diagnosis, balance clinical resources and demands, and ultimately optimize clinical diagnosis pathways and treatment strategies. Trial registration Clinicaltrial.gov, NCT04955756, Registered on July 9th 2021.

The physicochemical properties of sweet potato flour (SPF) can be modified by annealing. Native SPF was annealed in deionized water at a flour-to-water ratio of 1:3 (w/v) and temperatures of 50, 55, 60, or 65 °C for either 12 or 24 h. Annealed SPF maintained the A-type crystalline region and displayed increased relative crystallinity, increased pasting temperature, and decreased breakdown. SPF gels showed enhanced hardness together with better springiness when SPF was annealed at low temperature/long time or high temperature/short time. Annealed SPF hydrogel sheets contained larger, more uniform, and smoother pores than native ones. Noticeably, hydrogel sheets made of SPF annealed at 50 °C for 24 h exhibited advanced fracture strain from 93% to 176%. Overall, this work showed that annealing could modulate the characteristics of SPR hydrogels, which may widen the extent of applications in food industries. However, the annealing conditions need to be optimized.

Objective: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) still protracts worldwide. HFB30132A is an anti- SARS-CoV-2 monoclonal antibody purposely engineered for an extended half-life with neutralizing activity against majority of the virus variants identified so far. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of HFB30132A in healthy Chinese subjects.Methods: A phase 1, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. Twenty subjects were enrolled to Cohort 1 (1,000 mg dose level, 10 subjects) or Cohort 2 (2,000 mg dose level, 10 subjects). Subjects in each cohort were assigned randomly to receive a single intravenous (IV) dose of HFB30132A or placebo at a ratio of 8:2. Safety was assessed in terms of treatment emergent adverse events (TEAEs), vital signs, physical examination, laboratory tests, and ECG findings. PK parameters were measured and calculated appropriately. Anti-drug antibody (ADA) test was performed to detect anti-HFB30132A antibodies.Results: All subjects completed the study. Overall, 13 (65%) of the 20 subjects experienced TEAEs. The most common TEAEs were laboratory abnormalities (12 subjects [60%]), gastrointestinal disorders (6 subjects [30%]), and dizziness (4 subjects [20%]). All TEAEs were Grade 1 or Grade 2 in severity based on the criteria of Common Terminology Criteria for Adverse Events (CTCAE). Serum exposure (Cmax, AUC0-t, AUC0-∞) of HFB30132A increased with ascending dose. After single dose of 1,000 mg and 2000 mg HFB30132A, the mean Cmax was 570.18 μg/mL and 898.65 μg/mL, the mean AUC0-t value was 644,749.42 h*μg/mL and 1,046,209.06 h*μg/mL, and the mean AUC0-∞ value was 806,127.47 h*μg/mL and 1,299,190.74 h*μg/mL, respectively. HFB30132A showed low clearance ranging from 1.38 to 1.59 mL/h, and a long terminal elimination half-life (t½) of 89–107 days. ADA test did not detect any anti-HFB30132A antibodiesConclusion: HFB30132A was safe and generally well-tolerated after single IV dose of 1,000 mg or 2000 mg in healthy Chinese adults. HFB30132A did not induce immunogenic response in this study. Our data support further clinical development of HFB30132A.Clinical Trial Registration:https://clinicaltrials.gov, identifier: NCT05275660.

BackgroundThe neutrophil to lymphocyte ratio (NLR) is a cost-effective and easily identifiable inflammatory biomarker that has been shown to be closely associated with tumor prognosis and predict survival in patients with multiple malignancies. However, the predictive value of NLR in patients with gastric cancer (GC) treated with immune checkpoint inhibitors (ICIs) has not been fully explored. Therefore, we conducted a meta-analysis to explore the potential of NLR as a predictor of survival in this population.MethodsWe systematically searched the PubMed, Cochrane Library, and EMBASE databases from inception to the present for observational researches on NLR and its relationship with progression or survival in GC patients receiving ICIs. To assess the prognostic significance of NLR on overall survival (OS) or progression-free survival (PFS), we used fixed or random-effect models to derive and combine hazard ratios (HRs) with 95% confidence intervals (CIs). We also examined the relationship between NLR and treatment efficacy by calculating relative risks (RRs) with 95% CIs for objective response rate (ORR) and disease control rate (DCR) in patients with GC receiving ICIs.ResultsNine studies of 806 patients were eligible. OS and PFS data were obtained from 9 and 5 studies, respectively. In nine studies, NLR was associated with poor survival, the pooled HR was 1.98 (95% CI 1.67- 2.35, p < 0.001), indicating a significant association between high NLR and worse OS. We conducted subgroup analyses based on study characteristics to confirm the robustness of our findings. A relationship between NLR and PFS were reported in five studies with a HR of 1.49 (95% CI 0.99- 2.23, p = 0.056), which was not significantly associated. Pooling four studies that examined the correlation between NLR and ORR/DCR in GC patients, we observed a significant correlation between NLR and ORR (RR = 0.51, p = 0.003), but no significant correlation between NLR and DCR (RR = 0.48, p = 0.111).ConclusionIn summary, this meta-analysis indicates that increased NLR is significantly linked to worse OS in patients with GC receiving ICIs. In addition, lowering NLR can improve ORR. Thus, NLR can serve as a predictor for prognosis and treatment response in GC patients treated with ICIs. Nevertheless, further high-quality prospective studies are required to verify our findings in the future.

Abstract Background The G8 rotavirus genotype has been detected frequently in children in many countries and even became the predominant strain in sub-Saharan African countries, while there are currently no reports from China. In this study we described the genetic characteristics and evolutionary relationship between rotavirus strains from Guangzhou in China and the epidemic rotavirus strains derived from GenBank, 2020–2021. Methods Virus isolation and subsequent next-generation sequencing were performed for confirmed G8P[8] specimens. The genetic characteristics and evolutionary relationship were analyzed in comparison with epidemic rotavirus sequences obtained from GenBank. Results The two Guangzhou G8 strains were DS-1-like with the closest genetic distance to strains circulating in Southeast Asia. The VP7 genes of the two strains were derived from a human, not an animal G8 rotavirus. Large genetic distances in several genes suggested that the Guangzhou strains may not have been transmitted directly from Southeast Asian countries, but have emerged following reassortment events. Conclusions We report the whole genome sequence information of G8P[8] rotaviruses recently detected in China; their clinical and epidemiological significance remains to be explored further.

ABSTRACT Accurate and timely etiological diagnosis is crucial for bloodstream infections (BSIs) due to their high disability and mortality. We conducted a single-center prospective cohort study to compare the digital droplet PCR (ddPCR) assay with traditional blood culture. A total of 169 blood samples from 122 patients with suspected BSIs were collected, mostly from the department of infectious diseases, the emergency department, and the intensive care units, and the clinical data were also recorded. Nucleic acid was extracted from the blood samples, and a 5-fluorescent-channel droplet digital PCR assay was performed and then fed back with the pathogen and its copies. In BSI patients, ddPCR reported an overall 85.71% (12/14) (95% confidence interval [CI], 56.15 to 97.48%) sensitivity, 100% (7/7) (95% CI, 56.09 to 100.00%) and 71.43% (5/7) (95% CI, 30.26 to 94.89%) sensitivity in patients without empirical treatment and in empirically treated patients, respectively. Compared to traditional blood culture, the overall detection rate of ddPCR was significantly higher, 11.27% (16/142) (95% CI, 6.78 to 17.93%) versus 30.28% (43/142) (95% CI, 23.01 to 38.64%), and the extra detection rate of ddPCR was 19.01% (27/142) (95% CI, 13.11 to 26.63%). Of the ddPCR-positive culture-negative cases, 74.19% (23/31) (95% CI, 55.07 to 87.46%) were consistent with the final clinical diagnosis, including 10 bacteria and fungi. The detection rate of ddPCR was significantly higher in patients with white blood cell (WBC) counts of >10 · 109/L, C-reactive protein (CRP) of >70 mg/L, or procalcitonin (PCT) of >0.9 ng/L. Pathogen loads detected by ddPCR are correlated with WBC, CRP, and especially, PCT levels, precisely and rapidly reflecting clinical disease progression. ddPCR has an important guiding value for the clinical use of antibiotics to achieve the best pathogen coverage and the antibacterial effect. Collectively, ddPCR showed a great diagnostic performance in BSIs and had an overall higher detection rate than blood culture. In addition, ddPCR could be used to dynamically monitor the disease progression and provide medication guidance on antibiotic use. IMPORTANCE ddPCR is a promising method to address the current challenges of BSI diagnosis and precise treatment, as it is highly efficient in DNA detection. It shortens the identification of BSI-related pathogens from several days of traditional bacterial culture to 4 to 5 h. It is extremely sensitive and more tolerant to PCR inhibitors, which may facilitate the amplification and enable the detection of a meager amount of DNA fragments in detecting BSI-related pathogens and drug-resistant genes. It can identify almost 20 pathogens in one reaction, which reduces the usage of clinical blood samples to no more than 2 mL. Additionally, dynamic monitoring, assessment of pathogens, and antibiotic resistance genes in patients could be used to guide timely and precise adjustment of antimicrobial prescription. The short turnaround time of ddPCR may have the potential to guide antimicrobial treatment in the very early stage of sepsis and reduce the mortality and disability rate of sepsis.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) results in high susceptibility to infection. Although granulocytic myeloid-derived suppressor cells (gMDSC) are elevated in patients with HBV-ACLF, their role in HBV-ACLF pathogenesis is unknown. To elucidate the mechanism of gMDSC expansion and susceptibility to infection in HBV-ACLF patients, we analyzed the proportion of gMDSC in the peripheral blood and organ tissues of patients with HBV-ACLF and an ACLF mouse model established by continuous injection (eight times) of Concanavalin by flow cytometry and immunohistochemistry. We found that the proportion of gMDSC increased significantly in the blood and liver of patients with HBV-ACLF. This increase was positively correlated with disease severity, prognosis, and infection. gMDSC percentages were higher in peripheral blood, liver, spleen, and bone marrow than control levels in the ACLF mouse model. Immunofluorescence revealed that the gMDSC count increased in the liver of patients with HBV-ACLF as well as in the liver and spleen of ACLF mice. We further exposed peripheral blood monocyte cells from healthy donors to plasma from HBV-ACLF patients, recombinant cytokines, or their inhibitor, and found that TNF-α led to gMDSC expansion and significant upregulation of indoleamine 2, 3-dioxygenase (IDO), while blocking TNF-α signaling decreased gMDSC. Moreover, we detected proliferation and cytokine secretion of T lymphocytes when purified gMDSC was co-cultured with Pan T cells or IDO inhibitor and found that TNF-α-induced gMDSC inhibited T cell proliferation and interferon-γ production through the IDO signaling pathway. Lastly, the ability of gMDSC to phagocytose bacteria was low in patients with HBV-ACLF. Our findings elucidate HBV-ACLF pathogenesis and provide potential therapeutic targets.

Abstract. We present a case of acute-on-chronic liver failure (ACLF) in a patient with hepatitis B virus (HBV)-related decompensated cirrhosis and coronavirus disease 2019 (COVID-19). A 58-year-old woman with HBV-related and decompensated cirrhosis without any anti-viral treatment previously was admitted to the hospital due to a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On admission, she was in stable condition. Thoracic computed tomography (CT) and laboratory findings showed no significant abnormalities. Entecavir was initiated promptly for HBV, while antiviral therapy and supportive treatment were initiated for COVID-19. Her lung infection exacerbated after 10 days of recurrent fever despite treatments, and there were signs of HBV reactivation. ACLF and multiple organ dysfunction syndrome developed rapidly from day 10 to day 19. The patient's clinical deterioration was also consistent with pneumonia progression and elevated interleukin 6 levels. SARS-CoV-2 likely precipitated ACLF in cirrhotic patients, either by inducing HBV flare or serving as an acute insult directly. This study discussed the underlying mechanisms of this process and management details. Monitoring HBV status is necessary, and inflammatory parameters might be valuable. HBV suppression should be initiated early, and variceal hemorrhage primary prevention might be beneficial in COVID-19 patients with cirrhosis.

The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naïve SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.

Abstract In current power grids, a massive amount of power equipment raises various emerging requirements, e.g., data perception, information transmission, and real-time control. The existing cloud computing paradigm is stubborn to address issues and challenges such as rapid response and local autonomy. Microgrids contain diverse and adjustable power components, making the power system complex and difficult to optimize. The existing traditional adjusting methods are manual and centralized, which requires many human resources with expert experience. The adjustment method based on edge intelligence can effectively leverage ubiquitous computing capacities to provide distributed intelligent solutions with lots of research issues to be reckoned with. To address this challenge, we consider a power control framework combining edge computing and reinforcement learning, which makes full use of edge nodes to sense network state and control power equipment to achieve the goal of fast response and local autonomy. Additionally, we focus on the non-convergence problem of power flow calculation, and combine deep reinforcement learning and multi-agent methods to realize intelligent decisions, with designing the model such as state, action, and reward. Our method improves the efficiency and scalability compared with baseline methods. The simulation results demonstrate the effectiveness of our method with intelligent adjusting and stable operation under various conditions.

A booster vaccination is called for constraining the evolving epidemic of SARS-CoV-2. However, the necessity of a new COVID-19 vaccine is currently unclear. To compare the effect of an Omicron-matched S DNA vaccine and an ancestral S DNA vaccine in boosting cross-reactive immunities, we firstly immunized mice with two-dose of a DNA vaccine encoding the spike protein of the ancestral Wuhan strain. Then the mice were boosted with DNA vaccines encoding spike proteins of either the Wuhan strain or the Omicron variant. Specific antibody and T cell responses were measured at 4 weeks post boost. Our data showed that the Omicron-matched vaccine efficiently boosted RBD binding antibody and neutralizing antibody responses against both the Delta and the Omicron variants. Of note, antibody responses against the Omicron variant elicited by the Omicron-matched vaccine were much stronger than those induced by the ancestral S DNA vaccine. Meanwhile, CD8+ T cell responses against both the ancestral Wuhan strain and the Omicron strain also tended to be higher in mice boosted by the Omicron-matched vaccine than those in mice boosted with the ancestral S DNA vaccine, albeit no significant difference was observed. Our findings suggest that an Omicron-matched vaccine is preferred for boosting cross-protective immunities.

Rotaviruses (RVs) are the leading cause of acute gastroenteritis in children, while histo-blood group antigens (HBGAs) are believed to be host attachment and susceptibility factors of RVs. A large case–control study nested in a population-based diarrhea surveillance targeting children

Key Points Currently bacterial and viral agents in the gastrointestinal tract are under-detected and poorly defined in developing countries. A new sensitive TAC assay provided comprehensive identification of microorganisms, including neglected pathogens, in Chinese children with moderate and severe diarrhea.

Recently, blockchain has elicited escalating attention from academia to industry. However, blockchain is still in its initial stage, and remains a great number of non-trivial problems to be delved before being used as a generic platform. The most intractable one is the scalability problem. The deep reinforcement learning empowered adaptivity can help the blockchain network break through the bottleneck. In this paper, we study a deep reinforcement learning empowered adaptivity approach for future blockchain networks, so as to improve the scalability and meet the requirements of different users. Specifically, rather than using one consensus protocol as the best fit one, the blockchain networks launch different consensus protocols, based on users’ quality of service (QoS) requirements. To this end, we quantify four consensus protocols. Additionally, the blockchain networks are heavily hampered by the limited computation and bandwidth resources. We also dynamically allocate computation and bandwidth resources to the blockchain networks. Then we formulate these thress items, i.e., the selection of consensus protocols, computation resource, and network bandwidth resource, as a joint optimization problem. A deep reinforcement learning approach is used to solve this problem. Simulation results are presented to show the effectiveness of our proposed scheme.

Design: A prospective multicentre study was conducted to compare the diagnostic accuracy of the GeneXpert MTB/RIF Ultra (Xpert Ultra) and cell-free DNA (cfDNA) assay for tuberculous meningitis (TBM) in China. Methods: A prospective cohort study was conducted among individuals with symptoms suggestive of TBM registered in three TB specialised hospitals in China between June 2018 and January 2019. Results: Overall, 84 patients suggestive of TBM were included in this analysis between June 2018 and January 2019. Using microbiological evidence as reference, the sensitivity/specificity for the diagnostic tests were Xpert Ultra 93.3%/100%, cfDNA 93.3%/92.6% and mycobacteria growth indicator tube (MGIT) culture 13.3%/100%. In addition, the sensitivity of culture was 6.7% when using clinical diagnosis criteria as the gold standard. Xpert Ultra correctly identified 28 cases as TBM, indicating a sensitivity of 46.7%. Notably, four additional TBM cases were detected by cfDNA compared with Xpert Ultra, yielding an overall sensitivity of 53.3%. Statistical analysis revealed that the sensitivity of Xpert Ultra and cfDNA was significantly higher than that of culture. Conclusions: The data demonstrate that Xpert Ultra and cfDNA assay showed optimal sensitivity compared with MGIT culture. In addition, there was no significant correlation between bacterial load and TBM severity in the participants.

ABSTRACTObjectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P

Background: Despite the considerable disease burden caused by the disease, rotavirus vaccine has not been introduced into routine national immunization schedule, and norovirus vaccines are being developed without a comprehensive understanding of gastroenteritis epidemiology. To bridge this knowledge gap, we investigated the disease burden of viral gastroenteritis in rural China. Methods: Between October 2011 and December 2013, population-based surveillance was conducted in Zhengding and Sanjiang counties in China. Stool samples were collected from children

It remains poorly defined whether any human miRNAs play protective roles during HIV infection. Here, focusing on a unique cohort of HIV-infected former blood donors, we identified miR-31 (hsa-miR-31) by comparative miRNA profiling as the only miRNA inversely correlating with disease progression. We further validated this association in two prospective cohort studies. Despite conservation during evolution, hsa-miR-31, unlike its mouse counterpart (mmu-miR-31), was downregulated in human T cell upon activation. Our ex vivo studies showed that inhibiting miR-31 in naïve CD4+ T cells promoted a transcriptional profile with activation signature. Consistent with this skewing effect, miR-31 inhibition led to remarkably increased susceptibility to HIV infection. The suppressive nature of miR-31 in CD4+ T cell activation was pinpointed to its ability to decrease T-bet, the key molecule governing IFN-γ production and activation of CD4+ T cells, by directly targeting the upstream STAT1 transcriptional factor for downregulation, thus blunting Th1 response. Our results implicated miR-31 as a useful biomarker for tracking HIV disease progression and, by demonstrating its importance in tuning the activation of CD4+ T cells, suggested that miR-31 may play critical roles in other physiological contexts where the CD4+ T cell homeostasis needs to be deliberately controlled.

Background: Metabolites are involved in biological process that govern the immune response to infection and vaccination. Knowledge of how metabolites interact with the immune system during immunization with the COVID-19 vaccine is limited. Here, we report that the serum metabolites are correlated with the magnitude of the antibody response in recipients receiving the inactivated COVID-19 vaccine, which provides critical information for studying metabolism regarding the human immune response to vaccination. Methods: 106 healthy volunteers without history of SARS-CoV-2 infection or vaccination were prospectively enrolled to receive the primary series of two doses of inactivated whole-virion SARS-CoV-2 vaccine. The serum samples were collected 2–4 weeks after the second dose. The magnitude of the anti-RBD antibody was quantified using surrogate virus neutralization tests. The profile of metabolites in serum was identified using untargeted metabolomics analysis. Results: The level of anti-RBD antibody 14–28 days after the second dose was significantly elevated and its interpersonal variability was diverse in a wide range. Thirty-two samples at extremes of the anti-RBD antibody titer were selected to discover the metabolic correlates. Two hundred and fifteen differential metabolites associated with antibody response independent of body mass index were identified. Pregnenolone and sphingolipid metabolism might be involved in the modulation of the human antibody response to the inactivated COVID-19 vaccine. Conclusion: We discovered key metabolites as well as those with a related functional significance that might modulate the human immune response to vaccination.

Abstract Background Split-thickness skin grafting is the current gold standard for the treatment of traumatic skin loss. However, for patients with extensive burns, split-thickness skin grafting is limited by donor skin availability. Grafting split-thickness skin minced into micrografts increases the expansion ratio but may reduce wound repair quality. Dermal substitutes such as Pelnac can enhance the healing of full-thickness skin wounds, but their application currently requires two surgeries. The present study investigated whether it is possible to repair full-thickness skin defects and improve wound healing quality in a single surgery using Pelnac as an overlay of minced split-thickness skin grafts in a rat model. Methods A full-thickness skin defect model was established using male Sprague-Dawley rats of 10 weeks old. The animals were randomly divided into control and experimental groups in which Vaseline gauze and Pelnac, respectively, were overlaid on minced split-thickness skin grafts to repair the defects. Wound healing rate and quality were compared between the two groups. For better illustration of the quality of wound healing, some results were compared with those obtained for normal skin of rats. Results We found that using Pelnac as an overlay for minced split-thickness skin grafts accelerated wound closure and stimulated cell proliferation and tissue angiogenesis. In addition, this approach enhanced collagen synthesis and increased the formation of basement membrane and dermis as well as the expression of growth factors related to wound healing while reducing scar formation. Conclusions Using minced split-thickness skin grafts overlaid with Pelnac enables the reconstruction of full-thickness skin defects in a single step and can increase the healing rate while improving the quality of wound healing.

Polarization sensitivity is a severe problem in photonic integration devices and chips based on the high-index contrast Si/SiO2 system. In this paper, a broadband silicon polarization splitter-rotator (PSR) comprised of a bi-level taper and a counter-tapered coupler is proposed with a large fabrication tolerance. The measured insertion loss is lower than 0.7 dB/0.73 dB for the wavelength range from 1470 to 1580 nm with a crosstalk lower than -12.1 dB/-14.7 dB for TE and TM polarization input, respectively. By integrating the PSR with silicon arrayed waveguide gratings and germanium photodetectors (PDs) on a single chip, a polarization-insensitive wavelength-division-multiplexing (WDM) receiver is demonstrated with a polarization-dependent loss as low as 1.21 dB. High-speed operations are also achieved with clear eyes at 10 Gb/s.

In this work, rutin (RT)–loaded zein–carboxymethyl starch (CMS) nanoparticles were successfully prepared by the antisolvent precipitation method. The effect of CMS on composite nanoparticles at different concentrations was studied. When the ratio of zein–RT–CMS was 10:1:30, the encapsulation efficiency (EE) was the highest, reaching 73.5%. At this ratio, the size of the composite nanoparticles was 196.47 nm, and the PDI was 0.13, showing excellent dispersibility. The results of fluorescence spectroscopy, FTIR, XRD, and CD showed that electrostatic interaction, hydrogen bonding, and hydrophobic interaction were the main driving forces for the formation of nanoparticles. It can be seen from the FE–SEM images that the zein–RT–CMS nanoparticles were spherical. With the increase in the CMS concentration, the particles gradually embedded in the cross–linked network of CMS (10:1:50). After RT was loaded on zein–CMS nanoparticles, the thermal stability and pH stability of RT were improved. The results showed that zein–CMS was an excellent encapsulation material for bioactive substances.

Anti-HBc IgG is usually recognized as a diagnostic marker of hepatitis B, while the functional role anti-HBc IgG in HBV infection has not been fully elucidated. In this study, we firstly investigated the relationship between the anti-HBc IgG responses and the replication of HBV using AAV8-1.3HBV infected C57BL/6N mice. Our data showed that the anti-HBc IgG responses at the early phase of infection correlated negatively with the concentrations of circulating HBsAg and HBV DNA at both the early and chronic phases of infection. This observation was confirmed by an independent experiment using AAV8-1.3HBV infected C57BL/6J mice. Furthermore, to comprehend the potential causal relationship between the anti-HBc IgG responses and HBV infection, mice were treated with an anti-HBc monoclonal antibody at three days post AAV8-1.3HBV infection. Our data showed that the anti-HBc mAb significantly suppressed the fold increase of circulating HBsAg level, and the protective effect was not affected by NK cell depletion. Collectively, our study demonstrated that anti-HBc antibodies occurring at the early phase of HBV infection may contribute to the constraint of the virus replication, which might be developed as an immunotherapy for hepatitis B.

Plant polyphenols have attracted considerable attention because of their key roles in preventing many diseases, including high blood sugar, high cholesterol, and cancer. A variety of functional foods have been designed and developed with plant polyphenols as the main active ingredients. Polyphenols mainly come from vegetables and fruits and can generally be divided according to their structure into flavonoids, astragalus, phenolic acids, and lignans. Polyphenols are a group of plant-derived functional food ingredients with different molecular structures and various biological activities including antioxidant, anti-inflammatory, and anticancer properties. However, many polyphenolic compounds have low oral bioavailability, which limits the application of polyphenols in nutraceuticals. Fortunately, green bio-based nanocarriers are well suited for encapsulating, protecting, and delivering polyphenols, thereby improving their bioavailability. In this paper, the health benefits of plant polyphenols in the prevention of various diseases are summarized, with a review of the research progress into bio-based nanocarriers for the improvement of the oral bioavailability of polyphenols. Polyphenols have great potential for application as key formulations in health and nutrition products. In the future, the development of food-grade delivery carriers for the encapsulation and delivery of polyphenolic compounds could well solve the limitations of poor water solubility and low bioavailability of polyphenols for practical applications.

Interleukin-12 receptor β1 (IL12RB1)-deficient individuals show increased susceptibilities to local or disseminated BCG infection and environmental mycobacteria infection. However, the low clinical penetrance of IL12RB1 deficiency and low recurrence rate of mycobacteria infection suggest that protective immunity still exists in this population. In this study, we investigated the mechanism of tuberculosis suppression using the IL12RB1-deficient mouse model. Our results manifested that Il12rb1−/− mice had significantly increased CFU counts in spleens and lungs, especially when BCG (Danish strain) was inoculated subcutaneously. The innate TNF-a and IFN-γ responses decreased, while the IL-17 responses increased significantly in the lungs of Il12rb1−/− mice. We also found that PPD-specific IFN-γ release was impaired in Il12rb1−/− mice, but the specific TNF-a release was not compromised, and the antibody responses were significantly enhanced. Moreover, correlation analyses revealed that both the innate and PPD-specific IFN-γ responses positively correlated with CFU counts, whereas the innate IL-12a levels negatively correlated with CFU counts in Il12rb1−/− mice lungs. Collectively, these findings proved that the adaptive immunities against mycobacteria are not completely nullified in Il12rb1−/− mice. Additionally, our results imply that IFN-γ responses alone might not be able to contain BCGitis in the setting of IL12RB1 deficiency.

Background: Current prognostic scores for pulmonary embolism (PE) were partly based on patients without PE confirmation via computed tomographic pulmonary angiography (CTPA), involving subjective parameters and complicated scoring methods. Therefore, we sought to develop an objective, accurate, and simple prognostic model in CTPA-confirmed patients to predict the risk of 30-day mortality. Methods: We retrospectively evaluated 509 patients with objectively confirmed PE by CTPA from 2010 to 2017 in the Minhang Hospital, which is affiliated to Fudan University. Patients were randomly divided into the training and validation cohorts. The primary end point was 30-day mortality. The secondary end points were the time to recovery in 30 days and mortality in 15 days. We compared the predictive performance of Pulmonary Embolism Severity Index (PESI), simplified PESI (sPESI), and the PE risk score we developed, called PERFORM. Findings: PERFORM (ranging from 0 to 12 score) is based on the patient's age, heart rate, and partial pressure of arterial oxygen. The area under the curve was 0.718 (95% confidence interval [CI], 0.627–0.809) for the training cohort and 0.906 (95% CI, 0.846–0.966) for the validation cohort. PERFORM was as good as PESI and sPESI in predicting mortality. Patients in the low-risk group (PERFORM score < 5) had a shorter time to recovery, whereas those in the high-risk group (PERFORM score ≥ 5) had a high mortality. Interpretation: PERFORM in CTPA-confirmed patients is an objective, accurate, and simple tool to predict the risk of 30-day mortality. Funding: Research Project of Shanghai Municipal Commission of Health and Family Planning (201740127), Shanghai Medical Key Subject Construction Project (ZK2019B08).