The Effectiveness of the 4P Nursing Model Combined with Amisulpride and Clozapine in the Management of Psychiatric Patients.

Objective: To study the clinical effectiveness of the 4P nursing model combined with Amisulpride and Clozapine in the management of psychiatric patients. Method: 100 patients with refractory schizophrenia treated in the Psychiatry department of Ganzhou People's Hospital from January 3, 2021, to January 4, 2022, were selected as the study subjects. They were randomly divided into observation and control groups, with 50 patients in each group. The clinical efficacy in the two groups was then assessed and compared using such parameters as the PANSS score, body mass index (BMI), blood lipid levels, incidence of side effects, and nursing satisfaction scores. Results: The difference in total treatment efficacy was statistically significant (χ2=11.724, 9.458, P ≤ .001, RR0.24, 95%CI (0.117-0.363)). The post-treatment PANSS score, positive symptom score, negative symptom score, and general pathological score treatment were all lower than the pre-treatment scores in both groups. The difference was statistically significant (RR0.12, 95%CI (0.098-0.203)). There was a reduction in the BMI of patients in the observation group after treatment, while there was an increase in that of patients in the control group. However, after treatment, there were significant reductions in the concentrations of T-CHO, LDL-C, and HDL-C in both groups (all P < .05, RR0.26, 95%CI (0.156-0.371)), with more significant reductions seen in the observation group than in the control group. The patients in the observation group recorded a much lower incidence of such side effects as drowsiness, nausea and vomiting, constipation, and weight gain and were more satisfied with the nursing they received as compared to their counterparts in the control group (all P < .05, RR0.28, 95%CI (0.171-0.351)). Conclusion: The 4P nursing model combined with Amisulpride and Clozapine can improve adherence to treatment, as well as the overall effectiveness of treatment. This nursing method has a high safety profile, improves the quality of life, and its use deserves more widespread promotion.

Tough, Eu3+ -Induced Luminescent Hydrogel as Flexible Chemosensor for Real-Time Quantitative Detection of Zn2+ Ion.

Herein, a novel tough luminescent hydrogel with Europium is fabricated using a facile copolymerization process by introducing 2,2':6',2-terpyridine (TPy) into a dual physical cross-linked hydrogel. The obtained P(NAGA-co-MAAc)/Eu/TPy (x) (x refers to the feed ratio of NAGA to MAAc) hydrogels not only show outstanding mechanical performances (fracture strength, ≈2.5 MPa), but also give a special ability of rapid detection to low concentrations of zinc ions. Attractively, the theoretical limits of detection (LOD) of the hydrogel sensors are calculated as 1.6 µm, which is acceptable within the WHO limit. Furthermore, the continuous change in fluorescence of P(NAGA-co-MAAc)/Eu/TPy (10) strips upon contact with Zn2+ can be clearly observed by the naked eyes with the aid of a portable UV lamp, resulting in semi-quantitative naked-eyes detection through a standard colorimetric card. Moreover, by identifying the RGB value of the hydrogel sensor, it can also realize quantitative analysis. Therefore, excellence in sensing, simplicity in structure, and convenience in using make P(NAGA-co-MAAc)/Eu/TPy (10) hydrogel as a superior fluorescent chemosensor of Zn2+ ions.

Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside.

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.

The potential of microRNA-126 in predicting disease risk, mortality of sepsis, and its correlation with inflammation and sepsis severity.

BACKGROUND: MicroRNA-126 (miR-126) has been investigated in autoimmune diseases and organ failures, whereas its implication in sepsis is rarely reported. Our study initially explored the value of miR-126 in diagnosing sepsis and predicting disease severity, degree of inflammation, and mortality. METHODS: Totally, 208 sepsis patients and 210 healthy controls were enrolled; then, their plasma samples were collected for detecting circulating miR-126 by quantitative polymerase chain reaction. For sepsis patients, their cytokine levels in plasma samples were detected by enzyme-linked immunosorbent assay. RESULTS: miR-126 was upregulated in sepsis patients compared with healthy controls, and it was of certain value in distinguishing sepsis patients from healthy controls (AUC: 0.726 (95% CI: 0.678-0.774)). miR-126 expression was positively correlated with acute physiology and chronic health evaluation II score, serum creatinine, and C-reactive protein but not albumin or white blood cell count in sepsis patients. Regarding cytokines, miR-126 was positively correlated with tumor necrosis factor-α, interleukin (IL)-6, and IL-8, but negatively correlated with IL-10 in sepsis patients. As for mortality, miR-126 expression was higher in deaths compared with survivors, and ROC curve displayed that it could predict mortality of sepsis patients to some extent with AUC of 0.619 (95% CI: 0.533-0.705). CONCLUSION: miR-126 potentially serves as an assistant diagnostic and prognostic biomarker for sepsis.

Herpes Simplex Virus 1 Specifically Targets Human CD1d Antigen Presentation To Enhance Its Pathogenicity.

Herpes simplex virus 1 (HSV-1) is one of the most prevalent herpesviruses in humans and represents a constant health threat to aged and immunocompromised populations. How HSV-1 interacts with the host immune system to efficiently establish infection and latency is only partially known. CD1d-restricted NKT cells are a critical arm of the host innate immune system and play potent roles in anti-infection and antitumor immune responses. We discovered previously that upon infection, HSV-1 rapidly and efficiently downregulates CD1d expression on the cell surface and suppresses the function of NKT cells. Furthermore, we identified the viral serine/threonine protein kinase US3 as a major viral factor downregulating CD1d during infection. Interestingly, neither HSV-1 nor its US3 protein efficiently inhibits mouse CD1d expression, suggesting that HSV-1 has coevolved with the human immune system to specifically suppress human CD1d (hCD1d) and NKT cell function for its pathogenesis. This is consistent with the fact that wild-type mice are mostly resistant to HSV-1 infection. On the other hand, in vivo infection of CD1d-humanized mice (hCD1d knock-in mice) showed that HSV-1 can indeed evade hCD1d function and establish infection in these mice. We also report here that US3-deficient viruses cannot efficiently infect hCD1d knock-in mice but infect mice lacking all NKT cells at a higher efficiency. Together, these studies supported HSV-1 evasion of human CD1d and NKT cell function as an important pathogenic factor for the virus. Our results also validated the potent roles of NKT cells in antiherpesvirus immune responses and pointed to the potential of NKT cell ligands as adjuvants for future vaccine development.IMPORTANCE Herpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We reported previously that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule, CD1d, so as to evade the antiviral function of NKT cells. Here we demonstrated that the virus has coevolved with the human CD1d and NKT cell system and that NKT cells indeed play potent roles in anti-HSV immune responses. These studies point to the great potential of exploring NKT cell ligands as adjuvants for HSV vaccines.

Onychomadesis and potential association with HFMD outbreak in a kindergarten in Hubei province, China, 2017.

BACKGROUND: In 2017, an outbreak of onychomadesis occurred in kindergarten H, Hubei province, China. We investigated the field to learn about the magnitude and reason of the outbreak. METHODS: The case definition was that a child with onychomadesis or transverse ridging (Beau's line) in fingernails and toenails without previous traumatic or systemic disease in kindergarten H from Sep. 1st to Nov. 30th, 2017. A retrospective cohort study was carried out to analyze the epidemiological relationship between onychomadesis and the hand-foot-mouth disease (HFMD) in Primary Class #2, kindergarten H. We also performed a serological survey for neutralizing antibodies against coxsackie virus A6 (CVA6), coxsackie virus A10 (CVA10) among 15 cases and six healthy children in the kindergarten. Meanwhile, some children were carried out with routine blood, fungal microscopic and microelement tests. Indoor environment examinations had been done for all classes. RESULTS: A total of 20 cases were identified in Kindergarten H. Seventy-five percent (15/20) cases occurred in Primary Class #2. Fifty-five percent of the cases (11/20) had suffered from HFMD within two months. The median time between onychomadesis and HFMD was 45 days (ranging from 31 to 58 days). A retrospective cohort study in Primary Class #2 showed the attack rate was 90.0% among 10 children who suffered from HFMD in the past two months compared to 30.0% among 20 children who didn't (Rate Ratio [RR] =3.0, 95% Confidence Interval [CI] =1.5-6.0). The positive rates of neutralizing antibodies were 66.7% for CVA6 and 26.7% for CVA10 in tested cases. The result of routine blood, fungal microscopic, microelements tests were normal in cases. The indicators of environment were within the normal range. CONCLUSION: The results of this study suggested that the outbreak of onychomadesis in Hubei province was probably associated with HFMD epidemic within two months.

Exploring core functional microbiota responsible for the production of volatile flavour during the traditional brewing of Wuyi Hong Qu glutinous rice wine.

The objective of this study was to explore the core functional microbiota for the production of volatile flavour during the traditional brewing of Wuyi Hong Qu glutinous rice wine, one of the most typical representatives of rice wine in China. Microbiological analysis based on high-throughput sequencing (HTS) technology demonstrated that bacteria of Lactobacillus, Bacillus, Leuconostoc, Lactococcus, Raoultella, Staphylococcus, Pediococcus, and Weissella, and fungi of Saccharomyces, Saccharomycopsis, Rhizopus, Monascus, Pichia, Wickerhamomyces, Candida, and Aspergillus were the predominant genera during the traditional fermentation process. Principal component analysis (PCA) based on the relative abundance showed that both of bacterial and fungal communities varied significantly in different fermentation phases. Some predominant microbial species or genera (including bacteria of Bacillus spp., Staphylococcus spp., Weissella spp., and P. acidilactici, and fungi of M. purpureus, R. oryzae, R. arrhizus var. arrhizus, and A. niger) were detected at the initial brewing stage, and their populations decreased as the fermentation progressed, while those of Lactobacillus, Gluconacetobacter, Leuconostoc, Pichia, Wickerhamomyces, and Saccharomyces increased to become the predominant genera at the final stage. A total of 79 volatile compounds were identified in traditional fermentation starters and during the traditional brewing process, mainly including esters, alcohols, acids, aldehydes, ketones, and phenols. Heatmaps and PCA also revealed the significant variances in the composition of volatile compounds among different samples. Furthermore, the potential correlations between microbiota succession and volatile flavour dynamics were explored through bidirectional orthogonal partial least squares (O2PLS) based correlation analysis. Three bacterial genera, namely, Gluconacetobacter, Lactobacillus, Lactococcus, and three fungal genera of Pichia, Wickerhamomyces, and Saccharomyces, were determined as the core functional microbiota for production of main volatile compounds in Wuyi Hong Qu glutinous rice wine. To conclude, information provided by this study is valuable to the development of effective strategies for the selection of beneficial bacterial and fungal strains to improve the quality of Wuyi Hong Qu glutinous rice wine.

A Subset of CD8αß+ Invariant NKT Cells in a Humanized Mouse Model.

Invariant NKT (iNKT) cells are unconventional innate-like T cells demonstrating potent antitumor function in conventional mouse models. However, the iNKT cell ligands have had limited efficacy in human antitumor clinical trials, mostly due to the profound differences in the properties and compositions of iNKT cells between the two species, including the presence of a CD8(+) subset of iNKT cells only in humans. To build reliable in vivo models for studying human iNKT cells, we recently developed the first humanized mouse model (hCD1d-KI) with human CD1d knocked in. To further humanize the mouse model, we now introduced the human invariant NKT TCRα-chain (Vα24Jα18) into the hCD1d-knockin mice. Similar to humans, this humanized mouse model developed a subset of CD8αß(+) iNKT cells among other human-like iNKT subsets. The presence of the CD8αß(+) iNKT cells in the thymus suggests that these cells developed in the thymus. In the periphery, these NKT cells showed a strong Th1-biased cytokine response and potent cytotoxicity for syngeneic tumor cells upon activation, as do human CD8αß(+) iNKT cells. The low binding avidity of iNKT TCRs to the human CD1d/lipid complex and high prevalence of Vß7 TCRß among the CD8(+) iNKT cells strongly point to a low avidity-based developmental program for these iNKT cells, which included the suppression of Th-POK and upregulation of eomesodermin transcriptional factors. Our establishment of this extensively humanized mouse model phenotypically and functionally reflecting the human CD1d/iNKT TCR system will greatly facilitate the future design and optimization of iNKT cell-based immunotherapies.

Herpes Simplex Virus 1 US3 Phosphorylates Cellular KIF3A To Downregulate CD1d Expression.

UNLABELLED: Herpes simplex virus 1 (HSV-1) causes one of the most prevalent herpesviral infections in humans and is the leading etiological agent of viral encephalitis and eye infections. Our understanding of how HSV-1 interacts with the host at the cellular and organismal levels is still limited. We and others previously reported that, upon infection, HSV-1 rapidly and efficiently downregulates CD1d cell surface expression and suppresses the function of NKT cells, a group of innate T cells with critical immunoregulatory function. The viral protein kinase US3 plays a major role in this immune evasion mechanism, and its kinase activity is required for this function. In this study, we investigated the cellular substrate(s) phosphorylated by US3 and how it mediates US3 suppression of CD1d recycling. We identified the type II kinesin motor protein KIF3A as a critical kinesin factor in the cell surface expression of CD1d. Interestingly, KIF3A is phosphorylated by US3 both in vitro and in infected cells. Mass spectrometry analysis of purified KIF3A showed that it is phosphorylated predominantly at serine 687 by US3. Ablation of this phosphorylation abolished US3-mediated downregulation of CD1d expression, suggesting that phosphorylation of KIF3A is the primary mechanism of HSV-1 suppression of CD1d expression by US3 protein. Understanding of the precise mechanism of viral modulation of CD1d expression will help to develop more efficient vaccines in the future to boost host NKT cell-mediated immune responses against herpesviruses. IMPORTANCE: Herpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We previously reported that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule CD1d to evade the antiviral function of NKT cells. Here we identified the key cellular motor protein KIF3A as a cellular substrate phosphorylated by US3, and this phosphorylation event mediates US3-induced immune evasion.

A new formula to calculate activity of superoxide dismutase in indirect assays.

To calculate superoxide dismutase (SOD) activity rapidly and accurately by indirect SOD assays, a formula based on the ratio of the catalytic speed of SOD to the reaction speed of the indicator with superoxide anion was deduced. The accuracy of this formula was compared with the conventional formula based on inhibition in five indirect SOD assays. The new formula was validated in nearly the entire SOD activity range, whereas the conventional formula was validated only during inhibition of 40-60%. This formula might also be used for the assays of other enzymes.

IkappaBbeta acts to inhibit and activate gene expression during the inflammatory response.

The activation of pro-inflammatory gene programs by nuclear factor-kappaB (NF-kappaB) is primarily regulated through cytoplasmic sequestration of NF-kappaB by the inhibitor of kappaB (IkappaB) family of proteins. IkappaBbeta, a major isoform of IkappaB, can sequester NF-kappaB in the cytoplasm, although its biological role remains unclear. Although cells lacking IkappaBbeta have been reported, in vivo studies have been limited and suggested redundancy between IkappaBalpha and IkappaBbeta. Like IkappaBalpha, IkappaBbeta is also inducibly degraded; however, upon stimulation by lipopolysaccharide (LPS), it is degraded slowly and re-synthesized as a hypophosphorylated form that can be detected in the nucleus. The crystal structure of IkappaBbeta bound to p65 suggested this complex might bind DNA. In vitro, hypophosphorylated IkappaBbeta can bind DNA with p65 and c-Rel, and the DNA-bound NF-kappaB:IkappaBbeta complexes are resistant to IkappaBalpha, suggesting hypophosphorylated, nuclear IkappaBbeta may prolong the expression of certain genes. Here we report that in vivo IkappaBbeta serves both to inhibit and facilitate the inflammatory response. IkappaBbeta degradation releases NF-kappaB dimers which upregulate pro-inflammatory target genes such as tumour necrosis factor-alpha (TNF-alpha). Surprisingly, absence of IkappaBbeta results in a dramatic reduction of TNF-alpha in response to LPS even though activation of NF-kappaB is normal. The inhibition of TNF-alpha messenger RNA (mRNA) expression correlates with the absence of nuclear, hypophosphorylated-IkappaBbeta bound to p65:c-Rel heterodimers at a specific kappaB site on the TNF-alpha promoter. Therefore IkappaBbeta acts through p65:c-Rel dimers to maintain prolonged expression of TNF-alpha. As a result, IkappaBbeta(-/-) mice are resistant to LPS-induced septic shock and collagen-induced arthritis. Blocking IkappaBbeta might be a promising new strategy for selectively inhibiting the chronic phase of TNF-alpha production during the inflammatory response.

Human CD1d knock-in mouse model demonstrates potent antitumor potential of human CD1d-restricted invariant natural killer T cells.

Despite a high degree of conservation, subtle but important differences exist between the CD1d antigen presentation pathways of humans and mice. These differences may account for the minimal success of natural killer T (NKT) cell-based antitumor therapies in human clinical trials, which contrast strongly with the powerful antitumor effects in conventional mouse models. To develop an accurate model for in vivo human CD1d (hCD1d) antigen presentation, we have generated a hCD1d knock-in (hCD1d-KI) mouse. In these mice, hCD1d is expressed in a native tissue distribution pattern and supports NKT cell development. Reduced numbers of invariant NKT (iNKT) cells were observed, but at an abundance comparable to that in most normal humans. These iNKT cells predominantly expressed mouse Vß8, the homolog of human Vß11, and phenotypically resembled human iNKT cells in their reduced expression of CD4. Importantly, iNKT cells in hCD1d knock-in mice exert a potent antitumor function in a melanoma challenge model. Our results show that replacement of mCD1d by hCD1d can select a population of functional iNKT cells closely resembling human iNKT cells. These hCD1d knock-in mice will allow more accurate in vivo modeling of human iNKT cell responses and will facilitate the preclinical assessment of iNKT cell-targeted antitumor therapies.

Preparation and evaluation of a sustained-release buckwheat noodle.

BACKGROUND: Different carbohydrates elicit various effects on the digestibility and the glucose release rate, so it is of interest to develop a sustained-release noodle based on the combination of different carbohydrates and reveal the sustained-release mechanism. RESULTS: The data obtained suggest that xanthan and konjac gum exhibited excellent and synergistic sustained-release properties, whereas cornstarch showed the lowest average digestion rate. The sustained release was particularly evident when the noodle consisted of the following components: 50 g of 25 g kg(-1) hydrophilic colloid mixture solution composed of a 1:1 mass ratio of xanthan:konjac gum and 100 g of reconstructed flour consisting of 200 g kg(-1) buckwheat flour, 400 g kg(-1) cornstarch, and 400 g kg(-1) plain flour. The morphological structure of noodles revealed that the composite hydrophilic colloids strengthened the interaction between the gluten network and starch granules. This buried starch within the three-dimensional structure thereby releasing glucose in a slow and sustained way. The most suitable model to describe glucose release from noodles was the Ritger-Peppas equation, which revealed that matrix erosion contributed to the release mechanism. CONCLUSION: These findings indicate that the controlled use of hydrophilic colloids and starches in manufacturing noodles could modulate the glucose sustained-release. © 2015 Society of Chemical Industry.

Acupuncture efficacy on ischemic stroke recovery: multicenter randomized controlled trial in China.

BACKGROUND AND PURPOSE: Acupuncture is a frequently used complementary treatment for ischemic stroke in China but the evidence available from previous randomized trials is inconclusive. The objective of this study was to assess the efficacy and safety of acupuncture in a more robustly designed larger scale trial. METHODS: This is a multicenter, single-blinded, randomized controlled trial. Eight hundred sixty-two hospitalized patients with limb paralysis between 3 to 10 days after ischemic stroke onset were allocated acupuncture plus standard care or standard care alone. The acupuncture was applied 5 times per week for 3 to 4 weeks. The primary outcomes were defined as follows: (1) death/disability according to Barthel index and (2) death/institutional care at 6 months. RESULTS: There was a tendency of fewer patients being dead or dependent in acupuncture group (80/385, 20.7%) than in control group (102/396, 25.8%) at 6 months (odds ratio, 0.75; 95% confidence interval, 0.54-1.05). The benefit was noted in subgroup receiving ≥10 sessions of acupuncture (odds ratio, 0.68; 95% confidence interval, 0.47-0.98). There was no statistical difference in death or institutional care between the 2 groups (odds ratio, 1.06; 95% confidence interval, 0.63-1.79). Severe adverse events occurred in 7.6% and 8.3% of patients in the 2 groups, respectively. CONCLUSIONS: Acupuncture seemed to be safe in the subacute phase of ischemic stroke. If the potential benefits observed are confirmed in future larger study, the health gain from wider use of the treatment could be substantial. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org/en/. Unique identifier: ChiCTR-TRC-11001353.

Purification and characterisation of a glutamic acid-containing peptide with calcium-binding capacity from whey protein hydrolysate.

The bioavailability of dietary ionised calcium is affected by intestinal basic environment. Calcium-binding peptides can form complexes with calcium to improve its absorption and bioavailability. The aim of this study was focused on isolation and characterisation of a calcium-binding peptide from whey protein hydrolysates. Whey protein was hydrolysed using Flavourzyme and Protamex with substrate to enzyme ratio of 25:1 (w/w) at 49 °C for 7 h. The calcium-binding peptide was isolated by DEAE anion-exchange chromatography, Sephadex G-25 gel filtration and reversed phase high-performance liquid chromatography (RP-HPLC). A purified peptide of molecular mass 204 Da with strong calcium binding ability was identified on chromatography/electrospray ionisation (LC/ESI) tandem mass spectrum to be Glu-Gly (EG) after analysis and alignment in database. The calcium binding capacity of EG reached 67·81 µg/mg, and the amount increased by 95% compared with whey protein hydrolysate complex. The UV and infrared spectrometer analysis demonstrated that the principal sites of calcium-binding corresponded to the carboxyl groups and carbonyl groups of glutamic acid. In addition, the amino group and peptide amino are also the related groups in the interaction between EG and calcium ion. Meanwhile, the sequestered calcium percentage experiment has proved that EG-Ca is significantly more stable than CaCl2 in human gastrointestinal tract in vitro. The findings suggest that the purified dipeptide has the potential to be used as ion-binding ingredient in dietary supplements.

[Investigating mechanism of toxicity reduction by combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata on terms of proteins self-assembly].

The combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata can increase efficacy and decrease toxicity. This study started from the phenomena of protein self-assembly in the mixed decoction of Glycyrrhizae Radix et Rhizoma with Aconiti Lateralis Radix Preparata. The attenuated mechanism was explored between the combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata by using the protein of Glycyrrhizae Radix et Rhizoma and aconitine which was the major toxic component of Aconiti Lateralis Radix Preparata. Glycyrrhizae Radix et Rhizoma protein with aconitine could form stable particles which particle mean diameter was (206.2 ± 2.02) nm and (238.20 ± 1.23) nm at pH 5.0 in normal temperature. Through the mouse acute toxicity experiment found that injection of aconitine monomer all mice were killed, and injection of Glycyrrhizae Radix et Rhizoma protein-aconitine particles with the same content of aconitine all mice survived. Survey the stability of Glycyrrhizae Radix et Rhizoma protein-aconitine shows that the colloid particles is stable at room temperature, and it has the possibility to candidate drug carrier. Glycyrrhizae Radix et Rhizoma protein can reduce the toxicity of aconitine through self-assembly.

Hydrogels with ultra-highly additive adjustable toughness under quasi-isochoric conditions.

Bioinspired smart hydrogels with additive-switchable mechanical properties have been attracting increasing attention in recent years. However, most existing hydrogel systems suffer from limited stiffening amplitude and dramatic volume change upon response to environmental triggers. Herein, we propose a novel strategy to prepare additive-responsive hydrogels with ultra-highly adjustable toughness under quasi-isochoric conditions. The key point lies in tuning the softening transition temperature of the hydrogels with non-covalent interactions between the polymer networks and additives, shifting the hydrogels from glassy to rubbery states. As a proof of concept, a variety of glassy hydrogels are prepared and exposed to additives to trigger responsive performances. Young's modulus of the same hydrogel demonstrates up to 36 000 times ultra-broad-range tunability, ranging from 0.0042 to 150 MPa in response to different additives. Meanwhile, negligible volume changes occur, keeping the hydrogels in quasi-isochoric conditions. Interestingly, the mechanical behaviors of the hydrogels manifest remarkable dependence on the additive type and concentration since both the Hofmeister effect and hydrophobicity of the additives play pivotal roles according to mechanism investigations. Furthermore, the regulation with additives reveals satisfactory reversibility and universality. Taken together, this simple and effective approach provides a novel strategy to fabricate hydrogels with highly tunable toughness for versatile applications, including spatially patterned conductive gels and anti-icing coatings.

Facile degradation of chitosan-sodium alginate-chromium (III) gel in relation to leather re-tanning and filling.

Natural polysaccharide hydrogel, exemplified by chitosan­sodium alginate (CS-SA), has been prevailing in adsorption of chromium (III) (Cr(III)) containing contaminant. However, the traditional desorption of CS-SA-Cr(III) to recycle the adsorbent faces the problems including chemical desorbents secondary pollution, resource waste of the terminal CS-SA adsorbents, and tedious work of reusing the desorbed Cr(III). Herein, the adsorption product, CS-SA-Cr(III) gel, was degraded to CS/SA/Cr(III) sol and applied in leather re-tanning and filling processes directly. To achieve this goal, three degradation methods were used to transform the gel to sol. Due to the excellent overall performance of the CS/SA/Cr(III)-HMD4 sol (obtained by the hydrothermal-mechanical degradation method for 4 h (HMD4)), including wide size and distribution range, moderate viscosity (54 ± 3.1 mPa·s), high electronegativity (-38.6 ± 5.8 mV), and good stability, the resultant leather after re-tanning and filling by the sol achieved fascinating properties such as good thermal stability (Ts, 116.8 ± 1.8 °C; Td, 94.2 ± 1.7 °C), mechanical performance (tensile strength, 6.9 ± 0.52 MPa; elongation at break, 95 ± 3.0 %), and superduper thickening rate (31.8 %). Moreover, the mechanism of good re-tanning and filling effects was deciphered. Therefore, this work intends to overcome the limitation of traditional desorption technology and further realizes the high-valued application of the exhausted CS-SA-Cr(III) in leather re-tanning and filling processes.

Herpes simplex virus 1 glycoprotein B and US3 collaborate to inhibit CD1d antigen presentation and NKT cell function.

Herpes simplex viruses (HSVs) are prevalent human pathogens that establish latency in human neuronal cells and efficiently evade the immune system. It has been a major medical challenge to eradicate them and, despite intensive efforts, an effective vaccine is not available. We previously showed that upon infection of antigen-presenting cells, HSV type 1 (HSV-1) rapidly and efficiently downregulates the major histocompatibility complex class I-like antigen-presenting molecule, CD1d, and potently inhibits its recognition by CD1d-restricted natural killer T (NKT) cells. It suppresses CD1d expression primarily by inhibiting its recycling to the cell surface after endocytosis. We identify here the viral glycoprotein B (gB) as the predominant CD1d-interacting protein. gB initiates the interaction with CD1d in the endoplasmic reticulum and stably associates with it throughout CD1d trafficking. However, an additional HSV-1 component, the serine-threonine kinase US3, is required for optimal CD1d downregulation. US3 expression in infected cells leads to gB enrichment in the trans-Golgi network (TGN) and enhances the relocalization of both gB and CD1d to this compartment, suggesting that following internalization CD1d is translocated from the endocytic pathway to the TGN by its association with gB. Importantly, both US3 and gB are required for efficient inhibition of CD1d antigen presentation and NKT cell activation. In summary, our results suggest that HSV-1 uses gB and US3 to rapidly inhibit NKT cell function in the initial antiviral response.

Modes of assay interference and the effectiveness of serum pretreatment approaches in detection of anti-HLA antibodies.

AIMS: Several modes of assay interference common to immunoassays affect solid-phase single-antigen bead-based immunoassays (SAB) used to detect antibodies against human leucocyte antigens (HLA). Best practice recommendations include methods to address assay interference, though the clinical impact and optimal approaches are undefined. We sought to evaluate assay interference in HLA SAB to identify an efficient approach for avoiding erroneous results. METHODS: Retrospective analysis of 14 059 patient samples tested for anti-HLA antibodies was performed. This included 4685 samples tested prior to implementation of serum pretreatment with EDTA and 4982 samples tested with routine EDTA treatment using the same testing algorithm. An algorithm for efficiently identifying and processing samples with suspected interference was evaluated in a separate cohort of 4392 EDTA-treated samples. RESULTS: EDTA serum pretreatment reduced assay interference, but did not eliminate all modes of interference. A protocol for identification and testing of samples with suspected interference facilitated efficient detection of interference while reducing the amount of additional testing required. CONCLUSIONS: Our data indicate that a single-method approach is insufficient to address all sources of interference in HLA SAB. A multimodal approach with a proactive screening is a more effective way to minimise risk of erroneous results.