Cloned antibodies from patients with HIT provide new clues to HIT pathogenesis.

Heparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction characterized by antibodies that recognize platelet factor 4/heparin complexes (PF4/H) and activate platelets to create a prothrombotic state. Although a high percentage of heparin-treated patients produce antibodies to PF4/H, only a subset also makes antibodies that are platelet activating (PA). A close correlation between PA antibodies and the likelihood of experiencing HIT has been demonstrated in clinical studies, but how PA (presumptively pathogenic) and nonactivating (NA) (presumptively benign) antibodies differ from each other at the molecular level is unknown. To address this issue, we cloned 7 PA and 47 NA PF4/H-binding antibodies from 6 patients with HIT and characterized their structural and functional properties. Findings showed that PA clones differed significantly from NA clones in possessing 1 of 2 heavy chain complementarity-determining region 3 (HCDR3) motifs, RX1-2R/KX1-2R/H (RKH) and YYYYY (Y5), in an unusually long complementarity-determining region 3 (≥20 residues). Mutagenic studies showed that modification of either motif in PA clones reduced or abolished their PA activity and that appropriate amino acid substitutions in HCDR3 of NA clones can cause them to become PA. Repertoire sequencing showed that the frequency of peripheral blood IgG+ B cells possessing RKH or Y5 was significantly higher in patients with HIT than in patients without HIT given heparin, indicating expansion of B cells possessing RKH or Y5 in HIT. These findings imply that antibodies possessing RKH or Y5 are relevant to HIT pathogenesis and suggest new approaches to diagnosis and treatment of this condition.

Omega-3 polyunsaturated fatty acids play a protective role in a mouse model of Parkinson's disease by increasing intestinal inducible Treg cells.

Parkinson's disease (PD) is defined as a progressive neurodegenerative disease in middle-aged and elderly people. The therapeutic effect of ω-3 PUFAs in several neurodegenerative diseases has been well recognized. Nevertheless, whether nutrition supplementing ω-3 PUFAs exerts a neuroprotective role in PD remains elusive. Bioinformatics revealed 2D chemical structural formula of three components. Mice received indicated treatment with saline, MPTP or ω-3 PUFAs according to grouping. Behavioral function of mice was measured through motor tests such as rearing, akinesia, and rotarod tests. OFT test measured anxiety-like behaviors of mice. Western blotting and TUNEL staining measured dopaminergic fibers and neurons of mice. Western blotting measured inflammation and apoptosis-related protein levels in mouse tissue. FACS measured iTreg cell proportion in colon and brain tissues of mice. ω-3 PUFAs repaired MPTP-stimulated motor function damage in PD mice. ω-3 PUFAs mitigated MPTP-stimulated comorbid anxiety in PD mice. ω-3 PUFAs relieved MPTP-stimulated deficits of dopaminergic fibers and neurons in PD mice. ω-3 PUFAs repressed MPTP-stimulated inflammation and apoptosis pathway activation in PD mice. ω-3 PUFAs repaired MPTP-stimulated immune function damage in PD mice. ω-3 PUFAs exert a protective role in PD mice through alleviating motor function impairment and neuroinflammation by increasing intestinal inducible Treg cells, which may provide a new direction for seeking targeted therapy plans for PD in humans.

Transcriptome-based analysis reveals a crucial role of the 20E/HR3 pathway in the diapause of Pieris rapae.

Pieris rapae is among the most damaging pests globally, and diapause makes it highly resistant to environmental stresses, playing a crucial role in the survival and reproduction of P. rapae while exacerbating the challenges of pest management and control. However, the mechanisms of its diapause regulation remain poorly understood. This research used RNA sequencing to profile the transcriptomes of three diapause phases (induction and preparation, initiation, maintenance) and synchronous nondiapause phases in P. rapae. During each comparison phase, 759, 1045, and 4721 genes were found to be differentially expressed. Among these, seven clock genes and seven pivotal hormone synthesis and metabolism genes were identified as having differential expression patterns in diapause type and nondiapause type. The weighted gene co-expression network analysis (WGCNA) revealed the red and blue modules as pivotal for diapause initiation, while the grey module was identified to be crucial to diapause maintenance. Meanwhile, the hub genes HDAC11, METLL16D, Dyw-like, GST, and so on, were identified within these hub modules. Moreover, an ecdysone downstream nuclear receptor gene, HR3, was found to be a shared transcription factor across all three phases. RNA interference of HR3 resulted in delayed pupal development, indicating its involvement in regulating pupal dipause in P. rapae. The further hormone assays revealed that the 20-hydroxyecdysone (20E) titer in diapause type pupae was lower than that in nondiapause type pupae, which exhibited a similar trend to HR3. When 20E was injected into diapause pupae, the HR3 expression levels were improved, and the pupal diapause were broken. These results indicate that the 20E/HR3 pathway is a critical pathway for the diapause regulation of P. rapae, and perturbing this pathway by ecdysone treatment or RNAi would result in the disruption of diapause. These findings provide initial insights into the molecular mechanisms of P. rapae diapause and suggest the potential use of ecdysone analogs and HR3 RNAi pesticides, which specifically target to diapause, as a means of pest control in P. rapae.

Prevalence and Residual Risk of HIV in Volunteer Blood Donors of Zhejiang Province, China, from 2018 to 2022.

Background: Blood safety levels have been significantly improved since the implementation of nucleic acid amplification technology (NAT) testing for blood donors. However, there remains a residual risk of transfusion transmission infections. This study aimed to evaluate the prevalence of HIV and its residual risk transmission among volunteer blood donors of Zhejiang Province, China, for five years after NAT implementation. Materials and Methods: All specimens and information were collected from voluntary unpaid donors at all blood services in Zhejiang Province, China, from January 2018 to December 2022. The HIV antibody or antigen and HIV RNA were detected using enzyme-linked immunosorbent assay and NAT, respectively. The HIV residual risk transmission was calculated using the incidence or window period model. Results: A total of 3,375,678 voluntary blood donors were detected, revealing an HIV prevalence of 9.92/100000. The HIV prevalence of blood donors in 12 blood services in Zhejiang Province was 6.11, 6.98, 7.45, 8.21, 8.36, 8.94, 9.04, 9.66, 9.73, 10.22, 11.80, and 12.47 per 100000 donors, without statistically significant difference observed among the services (p > 0.05). The HIV prevalence of males (15.49/100000) was significantly higher compared to females (1.95/100000; p < 0.05). There was an insignificant difference in HIV prevalence among blood donors of all different age groups (p > 0.05), but the HIV prevalence in the 26-35 age group and 18-25 age group was significantly higher compared to the 36-45 age group (p < 0.05). The difference in HIV prevalence between first-time blood donors (13.65/100,000) and repeat blood donors (6.78/100,000) was statistically significant (p < 0.05). From 2018 to 2022, the HIV residual risk in blood transfusion transmission was 0.266/100000. Conclusion: The prevalence of HIV among blood donors in Zhejiang Province, China, is associated with age, gender, and times of blood donation. The HIV residual risk in blood transfusion transmission remains low in the province, and increasing the rate of repeat blood donors is beneficial to improve blood safety.

Self-Reconstructed Two-Dimensional Cluster-Based Co-Organic Layer Heterojunctions for Enhanced Oxygen Evolution Reactions.

When it comes to an efficient catalytic oxygen evolution reaction (OER) in the production of renewable energy and chemicals, the construction of heterogeneous structures is crucial to break the linear scalar relationship of a single catalyst. This heterogeneous structure construction helps creatively achieve high activity and stability. However, the synthesis process of heterogeneous crystalline materials is often complex and challenging to capture and reproduce, which limits their application. Here, the dynamic process of structural changes in Co-MOFs in alkali was captured by in situ powder X-ray diffraction, FT-IR spectroscopy, and Raman spectroscopy, and several self-reconfigured MOF heterogeneous materials with different structures were stably isolated. The created ß-Co(OH)2/Co-MOF heterojunction structure facilitates rapid mass-charge transfer and exposure of active sites, which significantly enhanced OER activity. Experimental results show that this heterogeneous structure achieves a low overpotential of 333 mV at 10 mA cm-2. The findings provide new insights and directions for the search for highly reactive cobalt-based MOFs for sustainable energy technologies.

Tectorigenin: A Review of Its Sources, Pharmacology, Toxicity, and Pharmacokinetics.

Tectorigenin is a well-known natural flavonoid aglycone and an active component that exists in numerous plants. Growing evidence suggests that tectorigenin has multiple pharmacological effects, such as anticancer, antidiabetic, hepatoprotective, anti-inflammatory, antioxidative, antimicrobial, cardioprotective, and neuroprotective. These pharmacological properties provide the basis for the treatment of many kinds of illnesses, including several types of cancer, diabetes, hepatic fibrosis, osteoarthritis, Alzheimer's disease, etc. The purpose of this paper is to provide a comprehensive summary and review of the sources, extraction and synthesis, pharmacological effects, toxicity, pharmacokinetics, and delivery strategy aspects of tectorigenin. Tectorigenin may exert certain cytotoxicity, which is related to the administration time and concentration. Pharmacokinetic studies have demonstrated that the main metabolic pathways in rats for tectorigenin are glucuronidation, sulfation, demethylation and methoxylation, but that it exhibits poor bioavailability. From our perspective, further research on tectorigenin should cover: exploring the pharmacological targets and mechanisms of action; finding an appropriate concentration to balance pharmacological effects and toxicity; attempting diversified delivery strategies to improve the bioavailability; and structural modification to obtain tectorigenin derivatives with higher pharmacological activity.

The impact of nucleic acid testing to detect human immunodeficiency virus, hepatitis C virus, and hepatitis B virus yields from a single blood center in China with 10-years review.

BACKGROUND: Since 2010, the Blood Center of Zhejiang province, China, has conducted a pilot nucleic acid amplification testing (NAT) screening of blood donors for Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human immunodeficiency virus (HIV). This study aims to assess the results of NAT testing over 10 years to establish the effects and factors influencing NAT yields of HBV, HCV, and HIV. METHODS: Blood donations from seven different blood services were screened for HBV DNA, HCV RNA, and HIV RNA using 6 mini pools (6MP) or individual donation (ID)-NAT method between August 1, 2010, and December 31, 2019, at the NAT centralized screening center. We compared 3 transcription-mediated amplification (TMA) assays and 2 polymerase chain reaction (PCR) assays. Further, HBV, HCV, and HIV NAT yields were calculated and donor characteristics and prevalence of HBV NAT yields analyzed. Donors with HCV and HIV NAT yield were also followed up. RESULTS: 1916.31 per million donations were NAT screening positive overall. The NAT yields for HBV, HCV, HIV and non-discriminating reactive were 1062.90 per million, 0.97 per million, 1.45 per million, and 850.99 per million, respectively, which varied in the seven blood services and different years. HBV NAT yields were higher than those of HCV and HIV and varied across demographic groups. Risk factors included being male, old age, low education level, and first-time donors. We found no differences in NAT yields of HBV, HCV, and HIV between the 3 TMA and 2 PCR assays; nonetheless, statistically, significant differences were noted between the five assays. CONCLUSION: In summary, NAT screening in blood donations reduces the risk of transfusion-transmitted infections and shortens the window period for serological marker screening. Therefore, a sensitive NAT screening method, ID-NAT workflow, and recruitment of regular low-risk donors are critical for blood safety.

Investigation into the Antibacterial Mechanism of Biogenic Tellurium Nanoparticles and Precursor Tellurite.

Antibacterial tellurium nanoparticles have the advantages of high activity and biocompatibility. Microbial synthesis of Te nanoparticles is not only a green technology but builds new ecological relationships in diverse environments. However, the antibacterial mechanism of Te nanoparticles is largely unclear. In this study, we report the bacterial synthesis of rod-shaped Te nanoparticles (BioTe) with high antibacterial activity against Escherichia coli. Morphology and permeability examination indicates that membrane damage is the primary reason for the antibacterial activity of BioTe, rather than ROS production and DNA damage. Moreover, a comparison of transcriptome and relative phenotypes reveals the difference in antibacterial mechanisms between BioTe and tellurite. Based on our evidence, we propose an antibacterial mode of rod-shaped BioTe, in which positively charged BioTe interact with the cell membrane through electrostatic attraction and then penetrate the membrane by using their sharp ends. In contrast, tellurite toxicity might be involved in sulfur metabolism.

Perianal disease onset age is associated with distinct disease features and need for intestinal resection in perianal Crohn's disease: a ten-year hospital-based observational study in China.

BACKGROUND AND AIMS: The significance of different ages of perianal disease (PD) onset in patients with perianal Crohn's disease (PCD) remains unknown. We aimed to investigate the impact of paediatric-onset PD (POP) and adult-onset PD (AOP) on the Crohn's disease (CD) course in a Chinese cohort. METHODS: The medical records of diagnosed PCD patients from 2008 to 2018 were reviewed retrospectively. The cumulative incidence and predictors of intestinal resection were calculated using the Kaplan-Meier and logistic regression analysis. RESULTS: Complex perianal fistulas (71.7% vs 50.0%, p = 0.011) and infliximab (IFX) treatment (33.3% vs 22.0%, p = 0.044) were more common among the POP patients (age < 18 years old, n = 84). A younger PD onset age (15.1 ± 2.9 vs 30.2 ± 10.5 years, p < 0.001) and shorter PCD diagnostic delay (12 vs 24 months, p = 0.033) was found in the POP cohort. AOP patients (age ≥ 18 years old, n = 209) had a higher rate of current smoking (12.9% vs 4.8%, p = 0.040), stricturing behaviour (42.1% vs 27.4%, p = 0.024) and intestinal resection (21.1% vs 4.8%, p = 0.001). The cumulative probability of intestinal resection in AOP patients was higher than that in POP patients (p = 0.007). In multivariable analysis, AOP (OR: 4.939, 95% CI 1.538-15.855, p = 0.007), stricturing behaviour (OR: 1.810, 95% CI 1.008-3.251, p = 0.047) and rectal inflammation (OR: 3.166, 95% CI 1.119-8.959, p = 0.030) were predictive factors for CD-related intestinal resection in all PCD patients. AOP patients with complex perianal fistula (OR: 2.257, 95% CI 1.041-4.891, p = 0.039) and POP patients with rectal inflammation (OR: 3.166, 95% CI 1.119-8.959, p = 0.030) were more likely to suffer intestinal resection. The IFX administration significantly decreased the rate of intestinal resection in AOP patients (r = - 0.900, p = 0.037). CONCLUSIONS: The AOP patients have more complicated luminal disease and higher rate of intestinal resection than COP patients. The perianal diseases onset-age can provide clinical treatment guidance for individual management of CD patients.

Characteristic of HBV nucleic acid amplification testing yields from blood donors in China.

BACKGROUND: Nucleic acid amplification testing (NAT) for blood screening has been previously performed in some countries to determine NAT yields. The current study sought to explore the non-discriminating reactive NAT yields using individual-NAT (ID-NAT) and characteristics of HBV NAT yields through a 10-year retrospective analysis in Zhejiang, China. METHODS: Blood donations were analyzed using individual-NAT mode by the transcription-mediated amplification (TMA) method. Supplementary HBV serological tests were performed using chemiluminescent immunoassay, and HBV viral load assay was performed by real-time polymerase chain reaction. Follow-up studies were performed in partial donors with low HBV viral loads. RESULTS: Non-discriminating reactive NAT yields and HBV NAT yields varied in different years. The yields ranged from 853.73 per million to 2018.68 per million and 624.60 per million to 1669.50 per million, respectively. In the 476 NAT yields, 19 were probable window periods (WP), 33 probable occult hepatitis B virus infections (OBIs), 409 were confirmed OBIs and 15 were chronic HBV infections. ID-NAT results were categorized in four groups, and the findings showed that the levels of HBV DNA viral loads were different in the four different groups (χ2 = 275.02, p < 0.01). HBV viral load distribution was significantly different between anti-HBs positive and anti-HBc positive samples (χ2 = 49.429, p < 0.01). Notably, only 42.03% donors were NAT repeated positive in the 138 repeat donors' follow up tests. CONCLUSION: NAT screening of blood donations can reduce the risk of transfusion-transmitted HBV infections. Positive proportions of anti-HBs and anti-HBc are correlated with the HBV viral load level. However, low level of viral load donors pose risks in HBV NAT assays, and show fluctuating state for HBV viral load and leads to non-repeated NAT results during follow up studies.

Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated ß-cyclodextrin combining cinchona alkaloid moiety.

Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated ß-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated ß-cyclodextrin (ß-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than ß-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of ß-CD moiety, which lead to the different enantioseparation of ß-CD-QN-based CSP and ß-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding ß-CD-based CSP for certain samples.

A novel C2 symmetric chiral stationary phase with N-[(4-Methylphenyl)sulfonyl]-l-leucine as chiral side chains.

In this study, a series of chiral stationary phases based on N-[(4-methylphenyl)sulfonyl]-l-leucine amide, whose enantiorecognition property has never been studied, were synthesized. Their enantioseparation abilities were chromatographically evaluated by 67 enantiomers. The chiral stationary phase derived from N-[(4-methylphenyl)sulfonyl]-l-leucine showed much better enantioselectivities than that based on N-(4-methylbenzoyl)-l-leucine amide. The construction of C2 symmetric chiral structure greatly improved the enantiorecognition performance of the stationary phase. The C2 symmetric chiral stationary phase exhibited superior enantioresolutions to other chiral stationary phases for most of the chiral analytes, especially for the chiral analytes with C2 symmetric structures. By comparing the enantioseparations of the enantiomers with similar structures, the importance of hydrogen bond interaction, π-π interaction, and steric hindrance on enantiorecognition was elucidated. The enantiorecognition mechanism of trans-N,N'-(1,2-diphenyl-1,2-ethanediyl)bis-acetamide, which had an excellent separation factor on the C2 symmetric chiral stationary phase, was investigated by 1 H-NMR spectroscopy and 2D 1 H-1 H nuclear overhauser enhancement spectroscopy.

HPLC and SFC enantioseparation of (±)-Corey lactone diol: Impact of the amylose tris-(3,5-dimethylphenylcarbamate) coating amount on chiral preparation.

As an important intermediate of prostaglandins and entecavir, optically pure Corey lactone diol (CLD) has great value in the pharmaceutical industry. In this work, the enantioseparation of (±)-CLD was evaluated using high-performance liquid (HPLC) and supercritical fluid chromatography (SFC). In HPLC, the separations of CLD enantiomers on polysaccharide-based chiral stationary phases with both normal phase and polar organic phase were screened. And the conditions for the enantioseparation were optimized in HPLC and SFC, including the selection of mobile phase, temperature, back-pressure, and other conditions. More important, it was found that the chiral resolutions were greatly enhanced by the increase of the coating amount of ADMPC (amylose tris-(3,5-dimethylphenylcarbamate)) under both HPLC and SFC conditions, which can lead to the increase of the productivity and the decrease of the solvent consumption. The preparations of optically pure CLD were evaluated on a semi-preparative (2 × 25 cm) column packed with 30% ADMPC-coated CSP under HPLC and SFC conditions. Preparative performances in terms of kkd are 1.536 kg racemate/kg CSP/day and 1.248 kg racemate/kg CSP/day in HPLC and SFC, respectively.

[Application of Shared Decision Making on Birth Choice in a Primigravida Woman With Congenital Adrenal Hyperplasia].

Shared decision making was used by a primipara with congenital adrenal hyperplasia to make decisions related to her delivery plans and process. The four components of the holistic nursing assessment process (physical, mental, social and spiritual) were conducted by the author from January 9th, 2018 to April 8th, 2018. The major concerns of the subject were anxiety and conflicts related to medical decision making for her health problems. The Case-Centered Care Model and Patient Decision Aids were applied in medical discussions conducted during the period of nursing care. The subject was encouraged to express her feelings during the process. The completed information for the delivery process, including the risks and benefits for the disease, was provided to the subject in order to lower her anxiety, assist her to select the most-appropriate plan for delivery, and ensure high quality, secure nursing care. Using Patient Decision Aids in clinical practice to help pregnant women make the best decisions for their delivery plans is recommended in cases where the patient has congenital adrenal hyperplasia.

Novel chiral ionic liquids stationary phases for the enantiomer separation of chiral acid by high-performance liquid chromatography.

Novel chiral ionic liquid stationary phases based on chiral imidazolium were prepared. The ionic liquid chiral selector was synthesized by ring opening of cyclohexene oxide with imidazole or 5,6-dimethylbenzimidazole, and then chemically modified by different substitute groups. Chiral stationary phases were prepared by bonding to the surface of silica sphere through thioene "click" reaction. Their enantioselective separations of chiral acids were evaluated by high-performance liquid chromatography. The retention of acid sample was related to the counterion concentration and showed a typical ion exchange process. The chiral separation abilities of chiral stationary phases were greatly influenced by the substituent group on the chiral selector as well as the mobile phase, which indicated that, besides ion exchange, other interactions such as steric hindrance, π-π interaction, and hydrogen bonding are important for the enantioselectivity. In this report, the influence of bulk solvent components, the effects of varying concentration, and the type of the counterion as well as the proportion of acid and basic additives were investigated in detail.

Exposure to 2,4-dichlorophenoxyacetic acid induces oxidative stress and apoptosis in mouse testis.

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used worldwide. It has been associated with a variety of toxicities in rodents. In this study, male mice were orally administered 2,4-D at 50, 100 or 200mg/kg/day to investigate testicular toxicity and the possible mechanisms of action. Exposure to 2,4-D at high concentrations (100 and 200mg/kg/day) for 14 consecutive days caused spermatogenic disruption and seminiferous epithelial destruction. Furthermore, 2,4-D administration (100 and 200mg/kg/day) increased the formation of the lipid peroxidation product malondialdehyde and decreased activities of the antioxidant enzymes superoxide dismutase and catalase in the testis. Moreover, 2,4-D exposure up-regulated the expression of p53 and Bax protein and down-regulated the expression of Bcl-2 protein in the testis. These results demonstrate that oxidative stress and apoptosis may be involved in testicular toxicity induced by high concentrations of 2,4-D in mice.

Evaluation of an individual-donation nucleic acid amplification testing algorithm for detecting hepatitis B virus infection in Chinese blood donors.

BACKGROUND: This multicenter study was performed to evaluate the efficiency of a multiplex individual-donation nucleic acid amplification technology (ID-NAT) and discriminatory testing algorithm for detecting hepatitis B virus (HBV) infection in Chinese blood donors. STUDY DESIGN AND METHODS: A total of 1,205,796 hepatitis B surface antigen (HBsAg)-nonreactive donations from 10 blood centers were tested by ID-NAT using the Ultrio assay. Multiplex Ultrio-reactive donations were tested in the discriminatory tests as well as in quantitative polymerase chain reaction (qPCR) and in supplemental electrochemiluminescence immunoassays for HBsAg, hepatitis B surface antibody (anti-HBs), hepatitis B e antigen, and antibody to hepatitis B core antigen (anti-HBc). Meanwhile, a control group of 4317 Ultrio-nonreactive donations was tested for anti-HBc and anti-HBs. RESULTS: Of all donations, 2033 (0.17%) were reactive in the multiplex Ultrio assay. Among 1776 further tested samples, 548 (30.9%) were HBV discriminatory assay (dHBV)-reactive, while 1214 (68.4%) were nonreactive. Of 472 Ultrio+ and dHBV+ samples 86.2% were qPCR positive compared to 15.0% in 1046 Ultrio+ and dHBV- samples. The proportion of anti-HBc+ and anti-HBs- (potentially infectious) donations was higher in 409 Ultrio+ and dHBV+ than in 1028 Ultrio+ and dHBV- samples (51.3% vs. 31.1%, p < 0.001). The yield rate of Ultrio+, dHBV+, and qPCR+ donations was estimated at 1 in 2500, but at 1 in 1100 when all supplemental tests were taken into account assuming that 44% of detected donations by Ultrio were false reactive. CONCLUSIONS: A quarter of HBsAg-negative Ultrio+ and dHBV- donations in China are likely given by potentially infectious low-viral-load occult carriers. Although this has no implication for blood safety, the testing algorithm needs to be redesigned to more efficiently discriminate between true and false NAT reactivity.

Supramolecular self-assembled gold nanoparticle clusters for synergistic photothermal-chemo tumor therapy.

The combination of photothermal therapy and chemotherapy has emerged as a promising strategy to improve cancer therapeutic efficacy. However, developing a versatile nanoplatform that simultaneously possesses commendable photothermal effect and high drug encapsulation efficiency remains a challenging problem yet to be addressed. Herein, we report a facile supramolecular self-assembly strategy to construct gold nanoparticle clusters (AuNCs) for synergistic photothermal-chemo therapy. By utilizing the functional polysaccharide as a targeted ligand, hyaluronic acid-enriched AuNCs were endowed with targeting CD44 receptor overexpressed on the B16 cancer cells. Importantly, these hyaluronic acid modified AuNCs can shelter therapeutic cargo of doxorubicin (DOX) to aggregate larger nanoparticles via a host-guest interaction with the anchored ß-cyclodextrin, as a "nanocluster-bomb" (DOX@AuNCs). The in vitro results revealed that these DOX@AuNCs showed light-triggered drug release behavior and synergistic photothermal-chemo therapy. The improved efficacy of synergistic therapy was further demonstrated by treating a xenografted B16 tumor model in vivo. We envision that our multipronged design of DOX@AuNCs provides a potent theranostic platform for precise cancer therapy and could be further enriched by introducing different imaging probes and therapeutic drugs as appropriate suitable guest molecules.

Fecal microbiota related to postoperative endoscopic recurrence in patients with Crohn's disease.

Background: Postoperative recurrence (POR) remains a major challenge for patients with Crohn's disease (CD). Gut microbial dysbiosis has been reported to be involved in the pathogenesis of POR. This study aims to investigate the relationship between fecal microbiome and endoscopic recurrence in patients with CD after ileocolonic resection. Methods: This is a cross-sectional study. Fecal samples were collected from 52 patients with CD after surgical intervention from 6 to 12 months before endoscopic examination. Endoscopic recurrence was defined as Rutgeerts score ≥ i2. The microbiome was analyzed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. Results: A total of 52 patients were included and classified into POR (n = 27) and non-POR (n = 25) groups. Compared with the non-POR group, the POR group had a significantly lower community richness (Chao1 index: 106.5 vs 124, P = 0.013) and separated microbial community (P = 0.007 for Adonis, P = 0.032 for Anosim), combined with different distribution of 16 gut microbiotas and decrease of 11 predicted metabolic pathways (P < 0.05). Lactobacillus and Streptococcus were identified to closely correlate to non-POR (P < 0.05) after controlling for confounding factors. Kaplan-Meier analysis indicated that the patients with higher abundance of Streptococcus experienced longer remission periods (P < 0.01), but this was not for Lactobacillus. The predicted ethylmalonyl-coA pathway related to increased amount of succinate was positively correlated with Streptococcus (r > 0.5, P < 0.05). Conclusions: The characteristic alterations of fecal microbiota are associated with postoperative endoscopic recurrence in patients with CD; particularly, high abundance of Streptococcus may be closely related to endoscopic remission.

Postoperative leukocyte counts as a surrogate for surgical stress response in matched robot- and video-assisted thoracoscopic surgery cohorts of patients: A preliminary report.

The objective is to preliminary evaluated postoperative leukocyte counts as a surrogate for the surgical stress response in NSCLC patients who underwent RATS or VATS for further prospective analyses with proper assessment of surgical stress response and tissue trauma. We retrospectively analyzed patients with stageI-IIIA NSCLC who underwent RATS or VATS at a hospital between 8 May 2020 and 31 December 2021. Analysis of leukocytes (including neutrophils and lymphocytes) and albumin on postoperative days (PODs) 1 and 3 in patients with NSCLC treated with RATS or VATS after propensity score matching (PSM). In total, 1824 patients (565 RATS and 1259 VATS) were investigated. The two MIS groups differed significantly with regard to operative time (p < 0.001), chronic lung disease (p < 0.001), the type of pulmonary resection (p < 0.001), the excision site of lobectomy (p = 0.004), and histology of the tumor (p = 0.028). After PSM, leukocyte and neutrophil levels in the RATS group were lower than those in the VATS group on PODs 1 and 3, with those on POD 3 (p < 0.001) being particularly notable. While lymphocyte levels in the RATS group were significantly lower than those in the VATS group only at POD 1 (p = 0.016). There was no difference in albumin levels between the RATS and VATS groups on PODs 1 and 3. The surgical stress response and tissue trauma was less severe in NSCLC patients who underwent RATS than in those who underwent VATS, especially reflected in the neutrophils of leukocytes.