Safety evaluation and effects of dietary phlorotannins on the growth, health, and intestinal microbiota of Litopenaeus vannamei.

Phlorotannins are phenolic compounds with diverse biological activities, yet their efficacy in aquatic animals currently remains unclear. This investigation scrutinized the influence of phlorotannins on the growth, immunity, antioxidant capacity, and intestinal microbiota in Litopenaeus vannamei, concurrently evaluating the potential adverse effects of phlorotannins on L. vannamei. A base diet without phlorotannins supplementation was used as a control, and 4 groups of diets with different concentrations (0, 0.5, 1.0, 2.0 g kg-1) of phlorotannins were formulated and fed to juvenile shrimp (0.25 ± 0.01 g) for 60 days followed by a 24-h challenge with Vibrio parahaemolyticus with triplicate in each group. Compared with the control, dietary 2.0 g kg-1 phlorotannins significantly improved the growth of the shrimp. The activities of enzymes related to cellular immunity, humoral immunity, and antioxidants, along with a notable upregulation in the expression of related genes, significantly increased. After V. parahaemolyticus challenge, the cumulative survival rates of the shrimp demonstrated a positive correlation with elevated concentrations of phlorotannins. In addition, the abundance of Bacteroidetes and functional genes associated with metabolism increased in phlorotannins supplementation groups. Phlorotannins did not elicit any detrimental effects on the biological macromolecules or histological integrity of the hepatopancreas or intestines. Simultaneously, it led to a significant reduction in malondialdehyde content. All results indicated that phlorotannins at concentrations of 2.0 g kg-1 can be used as safe feed additives to promote the growth, stimulate the immune response, improve the antioxidant capacity and intestinal health of L. vannamei, and an protect shrimp from damage caused by oxidative stress.

Signal peptide-CUB-EGF-like repeat-containing protein 1-promoted FLT3 signaling is critical for the initiation and maintenance of MLL-rearranged acute leukemia.

A hallmark of mixed lineage leukemia gene-rearranged (MLL-r) acute myeloid leukemia that offers an opportunity for targeted therapy is addiction to protein tyrosine kinase signaling. One such signal is the receptor tyrosine kinase Fms-like receptor tyrosine kinase 3 (FLT3) upregulated by cooperation of the transcription factors homeobox A9 (HOXA9) and Meis homeobox 1 (MEIS1). Signal peptide-CUB-EGF-like repeat-containing protein (SCUBE) family proteins have previously been shown to act as a co-receptor for augmenting signaling activity of a receptor tyrosine kinase (e.g., vascular endothelial growth factor receptor). However, whether SCUBE1 is involved in the pathological activation of FLT3 during MLL-r leukemogenesis remains unknown. Here we first show that SCUBE1 is a direct target of HOXA9/MEIS1 that is highly expressed on the MLL-r cell surface and predicts poor prognosis in de novo acute myeloid leukemia. We further demonstrate, by using a conditional knockout mouse model, that Scube1 is required for both the initiation and maintenance of MLL-AF9-induced leukemogenesis in vivo. Further proteomic, molecular and biochemical analyses revealed that the membrane-tethered SCUBE1 binds to the FLT3 ligand and the extracellular ligand-binding domains of FLT3, thus facilitating activation of the signal axis FLT3-LYN (a non-receptor tyrosine kinase) to initiate leukemic growth and survival signals. Importantly, targeting surface SCUBE1 by an anti-SCUBE1 monomethyl auristatin E antibody-drug conjugate led to significantly decreased cell viability specifically in MLL-r leukemia. Our study indicates a novel function of SCUBE1 in leukemia and unravels the molecular mechanism of SCUBE1 in MLL-r acute myeloid leukemia. Thus, SCUBE1 is a potential therapeutic target for treating leukemia caused by MLL rearrangements.

Translation and validation of the Taiwanese SarQoL, a quality of life questionnaire specific to sarcopenia.

BACKGROUND: The Sarcopenia Quality of Life (SarQoL) questionnaire has been translated into various languages. This study validated the Taiwanese version of the SarQoL (SarQoL-TW) questionnaire. METHODS: Forward-backward translation was conducted, along with a test of the prefinal version of the translated questionnaire. To validate the psychometric properties of the questionnaire, 50 older adults with sarcopenia and 50 older adults without sarcopenia completed the SarQoL-TW, the Short Form12 Health Survey (SF-12), and the EQ-5D-3L questionnaire. Participants with sarcopenia were asked to complete the SarQoL-TW questionnaire once more after 2 weeks. Validating the psychometric properties of the SarQoL-TW questionnaire involved assessing its discriminative power, internal consistency, construct validity, test-retest reliability, and potential floor and ceiling effects. RESULTS: The SarQoL-TW questionnaire was translated without major difficulties. The psychometric analysis revealed that older adults with sarcopenia scored significantly lower on the SarQoL-TW, both overall and in some of the domains. The Cronbach's alpha of 0.846 indicated high internal consistency. The SarQoL-TW questionnaire correlated well with similar constructs on the SF-12 and EQ-5D-3L for convergent validity and correlated weakly with distinct domains for divergent validity, confirming its favorable construct validity. The test-retest reliability was excellent (intraclass correlation coefficient: 0.970). Neither floor nor ceiling effects were observed. CONCLUSION: The SarQoL-TW questionnaire is a reliable and valid questionnaire, useful for assessing quality of life in older adults with sarcopenia in clinical practice and research.

Dengue Virus Ribonucleic Acid Detection Rates in Blood Donors Correlate With Local Infection Incidences During a Dengue Outbreak in Taiwan.

BACKGROUND: Evidence for mitigation of transfusion-transmitted dengue informed by surveillance data is lacking. In this study, we evaluated the risk of positive dengue viral (DENV) ribonucleic acid (RNA) from blood transfusions during a large outbreak in Taiwan. METHODS: Serum collected from blood donors living in districts experiencing the dengue epidemic were tested for DENV RNA using a qualitative transcription-mediated nucleic acid amplification assay (TMA). The TMA-reactive specimens were further tested for immunoglobulin (Ig)M and IgG antibodies, nonstructural protein 1 (NS1) antigen, and viral RNA by reverse-transcription polymerase chain reaction. We estimated DENV RNA prevalence and the number of DENV infections among blood donors. RESULTS: A total of 4976 specimens were tested for DENV RNA, and 21 were TMA-reactive. The detection rate was 0.84 (95% confidence interval [CI], 0.15-4.73), 3.36 (95% CI, 1.31-8.60), and 6.19 (95% CI, 3.14-12.17) per 1000 donors in districts where the weekly dengue incidence was 5-50, 50-200, and 200 or more per 100 000 residents, respectively. Alanine aminotransferase screening only detected 4.4% of TMA-reactive donations. A total of 143 transfusion-transmitted DENV infections probably occurred during this outbreak, accounting for 9.2 in 10 000 dengue infections. CONCLUSIONS: Approximately 0.5%-1% of blood donations were DENV RNA positive in epidemic districts. The correlation of DENV RNA rates with dengue incidence may inform the design of effective control measures.

Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness.

BACKGROUND: We recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-ß receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown. METHOD: We performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, ingenuity pathway analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA (Lens culinaris agglutinin) blotting and LC-MS/MS (liquid chromatography-tandem mass spectrometry) analysis. RESULTS: Loss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity pathway analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvß5 or IL6ST might be crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial-mesenchymal transition and metastasis. CONCLUSIONS: Our report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis.

Design and synthesis of 4-anilinoquinazolines as Raf kinase inhibitors. Part 1. Selective B-Raf/B-RafV600E and potent EGFR/VEGFR2 inhibitory 4-(3-hydroxyanilino)-6-(1H-1,2,3-triazol-4-yl)quinazolines.

This paper presents the design and synthesis of 4-(3-hydroxyanilino)-6-(1H-1,2,3-triazol-4-yl)quinazolines of scaffold 9 as selective B-Raf/B-RafV600E and potent EGFR/VEGFR2 kinase inhibitors. Total 14 compounds of scaffold 9 having different side chains at the triazolyl group with/without fluoro substituents at the anilino group were synthesized and investigated. Among them, 9m with a 2-carbamoylethyl side chain and C-4'/C-6' difluoro substituents was the most potent, which selectively inhibited B-Raf (IC50: 57 nM) and B-RafV600E (IC50: 51 nM) over C-Raf (IC50: 1.0 µM). Compound 9m also actively inhibited EGFR (IC50: 73 nM) and VEGFR2 (IC50: 7.0 nM) but not EGFRT790M and PDGFR-ß (IC50: >10 µM). Despite having good potency for B-Raf and B-RafV600E in the enzymatic assays, 9m was less active to inhibit melanoma A375 cells which proliferate due to constitutively activated B-Raf600E. The inferior activity of 9m for A375 was similar to that of sorafenib (6), suggesting that 9m might bind to the inactive conformations of B-Raf and B-RafV600E. Docking simulations could thus be performed to reveal the binding poses of 9m in B-Raf, B-RafV600E, and VEGFR2 kinases.

Chikungunya infection: First autochthonous cases in Taiwan.

The first autochthonous case and the first outbreak of chikungunya in Taiwan occurred during July-October 2019, with a total of 21 cases confirmed. Genetic analysis revealed the strains belonged to East/Central/South African genotype and had 99.95%-100% identity with the strains from the imported cases from Myanmar in 2019. This event confirmed that the imported chikungunya cases has the potential to cause autochthonous transmission in Taiwan; intensified surveillance and vector control measures are essential to contain the outbreak.

Long-term quality of life after sepsis and predictors of quality of life in survivors with sepsis.

PURPOSE: To evaluate the quality of life among survivors after sepsis in 2 years, comparing with critical patients without sepsis and the general people, analyze the changes and the predictors of quality of life among septic survivors. METHODS: This prospective case-control study screened the intensive care unit (ICU) patients in Tianjin Third Central Hospital from January 2014 to October 2017, and the Chinese general population in the previous studies was also included. According to inclusion criteria and exclusion criteria, 306 patients with sepsis were enrolled as the observation group, and another 306 patients without sepsis in ICU during the same period, whose ages, gender and Charlson Comorbidity Index matched with observation group, were enrolled as the control group. At 3 mo, 12 mo, and 24 mo after discharge, the Mos 36-item Short Form Health Survey (SF-36), the Euroqol-5 dimension (EQ-5D), and the activities of daily living (ADL) were evaluated in face-to-face for the quality of life among survivors. RESULTS: There were 210 (68.6%) septic patients and 236 (77.1%) non-septic critically ill patients surviving. At 3 months after discharge, the observation and control groups had the similar demographic characteristics (age: 58.8 ± 18.1years vs. 57.5 ± 17.6 years, p = 0.542; male: 52.0% vs. 51.4%, p = 0.926). However, the observation group had higher acute physiology and chronic health evaluation II (APACHEII) scores, higher sequential organ failure assessment (SOFA) scores, longer hospital stay, and longer ICU stay than the control group did (p < 0.05). There were no significant differences in the eight dimensions of the SF36 scale, the EQ-5D health utility scores, and the activities of daily life scores between septic survivors and non-septic survivors (p > 0.05). In addition, compared with the quality of life of the Chinese general population (aged 55-64 years), the quality of life of septic patients were significantly lower at 3 months after discharge (p < 0.05). Comparing the quality of life of the ill patients who had been discharged at 3 mo and 24 mo, the general health improved statistically (p = 0.000) and clinically (score improvement > 5 points). Older age (OR, 1.050; 95% CI, 1.022-1.078, p = 0.000), female (OR, 3.375; 95% CI, 1.434-7.941, p = 0.005) and longer mechanical ventilation time (OR, 3.412; 95% CI, 1.413, 8.244, p = 0.006) were the risk factors for the quality of life of septic survivors. CONCLUSION: The long-term quality of life of septic survivors was similar to that of non-sepsis critically ill survivors. After discharge, the general health of sepsis improved overtime. Age, female and mechanical ventilation time (>5 days) were the predictors of the quality of life after sepsis.

FUT8 promotes breast cancer cell invasiveness by remodeling TGF-ß receptor core fucosylation.

BACKGROUND: Core fucosylation (addition of fucose in α-1,6-linkage to core N-acetylglucosamine of N-glycans) catalyzed by fucosyltransferase 8 (FUT8) is critical for signaling receptors involved in many physiological and pathological processes such as cell growth, adhesion, and tumor metastasis. Transforming growth factor-ß (TGF-ß)-induced epithelial-mesenchymal transition (EMT) regulates the invasion and metastasis of breast tumors. However, whether receptor core fucosylation affects TGF-ß signaling during breast cancer progression remains largely unknown. METHOD: In this study, gene expression profiling and western blot were used to validate the EMT-associated expression of FUT8. Lentivirus-mediated gain-of-function study, short hairpin RNA (shRNA) or CRISPR/Cas9-mediated loss-of-function studies and pharmacological inhibition of FUT8 were used to elucidate the molecular function of FUT8 during TGF-ß-induced EMT in breast carcinoma cells. In addition, lectin blot, luciferase assay, and in vitro ligand binding assay were employed to demonstrate the involvement of FUT8 in the TGF-ß1 signaling pathway. The role of FUT8 in breast cancer migration, invasion, and metastasis was confirmed using an in vitro transwell assay and mammary fat pad xenograft in vivo tumor model. RESULTS: Gene expression profiling analysis revealed that FUT8 is upregulated in TGF-ß-induced EMT; the process was associated with the migratory and invasive abilities of several breast carcinoma cell lines. Gain-of-function and loss-of-function studies demonstrated that FUT8 overexpression stimulated the EMT process, whereas FUT8 knockdown suppressed the invasiveness of highly aggressive breast carcinoma cells. Furthermore, TGF-ß receptor complexes might be core fucosylated by FUT8 to facilitate TGF-ß binding and enhance downstream signaling. Importantly, FUT8 inhibition suppressed the invasive ability of highly metastatic breast cancer cells and impaired their lung metastasis. CONCLUSIONS: Our results reveal a positive feedback mechanism of FUT8-mediated receptor core fucosylation that promotes TGF-ß signaling and EMT, thus stimulating breast cancer cell invasion and metastasis.

Imported Chikungunya Virus Strains, Taiwan, 2006-2014.

We identified 78 imported chikungunya cases in Taiwan during 2006-2014. Sixty-six (84.6%) cases were initially suspected to be dengue, which indicates the necessity for laboratory diagnostics in differentiation between dengue and chikungunya. Results also emphasize the need for active surveillance of febrile illness at points of entry.

Comparison of the pulmonary dead-space fraction derived from ventilator volumetric capnography and a validated equation in the survival prediction of patients with acute respiratory distress syndrome.

PURPOSE: This prospective observational study aims to evaluate the accuracy of dead-space fraction derived from the ventilator volumetric capnography (volumetric CO2) or a prediction equation to predict the survival of mechanically ventilated patients with acute respiratory distress syndrome (ARDS). METHODS: Consecutive VD/VT measurements were obtained based upon a prediction equation validated by Frankenfield et al for dead-space ventilation fraction: VD/VT = 0.320 + 0.0106 (PaCO2-ETCO2)⁺ 0.003 (RR)⁺0.0015 (age) in adult patients who had infection-related severe pneumonia and were confirmed as having ARDS. Here PaCO2 is the arterial partial pressure of carbon dioxide in mmHg; ETCO2, the end- tidal carbon dioxide measurement in mmHg; RR, respiratory rate per minute; and age in years. Once the patient had intubation, positive end expiratory pressure was adjusted and after Phigh reached a steady state, VD/VT was measured and recorded as the data for the first day. VD/VT measurement was repeated on days 2, 3, 4, 5 and 6. Meanwhile we collected dead-space fraction directly from the ventilator volu- metric CO2 and recorded it as Vd/Vt. We analyzed the changes in VD/VT and Vd/Vt over the 6-day period to determine their accuracy in predicting the survival of ARDS patients. RESULTS: Overall, 46 patients with ARDS met the inclusion criteria and 24 of them died. During the first 6 days of intubation, VD/VT was significantly higher in nonsurvivors on day 4 (0.70 ± 0.01 vs 0.57 ± 0.01), day 5 (0.73 ± 0.01 vs. 0.54 ± 0.01), and day 6 (0.73 ± 0.02 vs. 0.54 ± 0.01) (all p =0.000). Vd/Vt showed no significant difference on days 1e4 but it was much higher in nonsurvivors on day 5 (0.45 ± 0.04 vs. 0.41 ± 0.06) and day 6 (0.47 ± 0.05 vs. 0.40 ± 0.03) (both p=0.008). VD/VT on the fourth day was more accurate to predict survival than Vd/Vt. The area under the receiver-operating characteristic curve for VD/VT and Vd/Vt in evaluating ARDS patients survival was day 4 (0.974 ± 0.093 vs. 0.701 ± 0.023, p = 0.0024) with the 95% confidence interval being 0.857-0.999 vs. 0.525-0.841. CONCLUSION: Compared with Vd/Vt derived from ventilator volumetric CO2, VD/VT on day 4 calculated by Frankenfield et al's equation can more accurately predict the survival of ARDS patients.

SCUBE3 (signal peptide-CUB-EGF domain-containing protein 3) modulates fibroblast growth factor signaling during fast muscle development.

SCUBE3 (signal peptide CUB-EGF-like domain-containing protein 3) belongs to a newly identified secreted and cell membrane-associated SCUBE family, which is evolutionarily conserved in vertebrates. Scube3 is predominantly expressed in a variety of developing tissues in mice such as somites, neural tubes, and limb buds. However, its function during development remains unclear. In this study, we first showed that knockdown of SCUBE3 in C2C12 myoblasts inhibited FGF receptor 4 expression and FGF signaling, thus resulting in reduced myogenic differentiation. Furthermore, knockdown of zebrafish scube3 by antisense morpholino oligonucleotides specifically suppressed the expression of the myogenic marker myod1 within the lateral fast muscle precursors, whereas its expression in the adaxial slow muscle precursors was largely unaffected. Consistent with these findings, immunofluorescent staining of fast but not slow muscle myosin was markedly decreased in scube3 morphants. Further genetic studies identified fgf8 as a key regulator in scube3-mediated fast muscle differentiation in zebrafish. Biochemical and molecular analysis showed that SCUBE3 acts as a FGF co-receptor to augment FGF8 signaling. Scube3 may be a critical upstream regulator of fast fiber myogenesis by modulating fgf8 signaling during zebrafish embryogenesis.

Inhibition of the plasma SCUBE1, a novel platelet adhesive protein, protects mice against thrombosis.

OBJECTIVE: Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1), a secreted and surface-exposed glycoprotein on activated platelets, promotes platelet-platelet interaction and supports platelet-matrix adhesion. Its plasma level is a biomarker of platelet activation in acute thrombotic diseases. However, the exact roles of plasma SCUBE1 in vivo remain undefined. APPROACH AND RESULTS: We generated new mutant (Δ) mice lacking the soluble but retaining the membrane-bound form of SCUBE1. Plasma SCUBE1-depleted Δ/Δ mice showed normal hematologic and coagulant features and expression of major platelet receptors, but Δ/Δ platelet-rich plasma showed impaired platelet aggregation in response to ADP and collagen treatment. The addition of purified recombinant SCUBE1 protein restored the aggregation of platelets in Δ/Δ platelet-rich plasma and further enhanced platelet aggregation in +/+ platelet-rich plasma. Plasma deficiency of SCUBE1 diminished arterial thrombosis in mice and protected against lethal thromboembolism induced by collagen-epinephrine treatment. Last, antibodies directed against the epidermal growth factor-like repeats of SCUBE1, which are involved in trans-homophilic protein-protein interactions, protected mice against fatal thromboembolism without causing bleeding in vivo. CONCLUSIONS: We conclude that plasma SCUBE1 participates in platelet aggregation by bridging adjacent activated platelets in thrombosis. Blockade of soluble SCUBE1 might represent a novel antithrombotic strategy.

A gold nanoparticle-based label free colorimetric aptasensor for adenosine deaminase detection and inhibition assay.

A novel strategy for the fabrication of a colorimetric aptasensor using label free gold nanoparticles (AuNPs) is proposed in this work, and the strategy has been employed for the assay of adenosine deaminase (ADA) activity. The aptasensor consists of adenosine (AD) aptamer, AD and AuNPs. The design of the biosensor takes advantage of the special optical properties of AuNPs and the interaction between AuNPs and single-strand DNA. In the absence of ADA, the AuNPs are aggregated and are blue in color under appropriate salt concentration because of the grid structure of an AD aptamer when binding to AD, while in the presence of the analyte, AuNPs remain dispersed with red color under the same concentration of salt owing to ADA converting AD into inosine which has no affinity with the AD aptamer, thus allowing quantitative investigation of ADA activity. The present strategy is simple, cost-effective, selective and sensitive for ADA with a detection limit of 1.526 U L(-1), which is about one order of magnitude lower than that previously reported. In addition, a very low concentration of the inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) could generate a distinguishable response. Therefore, the AuNP-based colorimetric biosensor has great potential in the diagnosis of ADA-relevant diseases and drug screening.

Zebrafish scube1 (signal peptide-CUB (complement protein C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor) domain-containing protein 1) is involved in primitive hematopoiesis.

scube1 (signal peptide-CUB (complement protein C1r/C1s, Uegf, and Bmp1)-EGF domain-containing protein 1), the founding member of a novel secreted and cell surface SCUBE protein family, is expressed predominantly in various developing tissues in mice. However, its function in primitive hematopoiesis remains unknown. In this study, we identified and characterized zebrafish scube1 and analyzed its function by injecting antisense morpholino-oligonucleotide into embryos. Whole-mount in situ hybridization revealed that zebrafish scube1 mRNA is maternally expressed and widely distributed during early embryonic development. Knockdown of scube1 by morpholino-oligonucleotide down-regulated the expression of marker genes associated with early primitive hematopoietic precursors (scl) and erythroid (gata1 and hbbe1), as well as early (pu.1) and late (mpo and l-plastin) myelomonocytic lineages. However, the expression of an early endothelial marker fli1a and vascular morphogenesis appeared normal in scube1 morphants. Overexpression of bone morphogenetic protein (bmp) rescued the expression of scl in the posterior lateral mesoderm during early primitive hematopoiesis in scube1 morphants. Biochemical and molecular analysis revealed that Scube1 could be a BMP co-receptor to augment BMP signaling. Our results suggest that scube1 is critical for and functions at the top of the regulatory hierarchy of primitive hematopoiesis by modulating BMP activity during zebrafish embryogenesis.

Impact of nutritional support on immunity, nutrition, inflammation, and outcomes in elderly gastric cancer patients after surgery.

BACKGROUND: Postoperative rehabilitation of elderly patients with gastric cancer has always been the focus of clinical attention. Whether the intervention by a full-course nutritional support team can have a positive impact on the postoperative immune function, nutritional status, inflammatory response, and clinical outcomes of this special population has not yet been fully verified. AIM: To evaluate the impact of full-course nutritional support on postoperative comprehensive symptoms in elderly patients with gastric cancer. METHODS: This is a retrospective study, including 60 elderly gastric cancer patients aged 70 years and above, divided into a nutritional support group and a control group. The nutritional support group received full postoperative nutritional support, including individualized meal formulation, and intravenous and parenteral nutrition supplementation, and was regularly evaluated and adjusted by a professional nutrition team. The control group received routine postoperative care. RESULTS: After intervention, the proportion of CD4+ lymphocytes (25.3% ± 3.1% vs 21.8% ± 2.9%, P < 0.05) and the level of immunoglobulin G (12.5 G/L ± 2.3 G/L vs 10.2 G/L ± 1.8 G/L, P < 0.01) were significantly higher in the nutritional support group than in the control group; the changes in body weight (-0.5 kg ± 0.8 kg vs -1.8 kg ± 0.9 kg, P < 0.05) and body mass index (-0.2 ± 0.3 vs -0.7 ± 0.4, P < 0.05) were less significant in the nutritional support group than in the control group; and the level of C-reactive protein (1.2 mg/L ± 0.4 mg/L vs 2.5 mg/L ± 0.6 mg/L, P < 0.01) and WBC count (7.2 × 109/L ± 1.5 × 109/L vs 9.8 × 109/L ± 2.0 × 109/L, P < 0.01) were significantly lower in the nutritional support group than in the control group. In addition, patients in the nutritional support group had a shorter hospital stay (10.3 d ± 2.1 d vs 14.8 d ± 3.6 d, P < 0.05) and lower incidence of infection (15% vs 35%, P < 0.05) in those of the control group. CONCLUSION: The intervention by the nutritional support team has a positive impact on postoperative immune function, nutritional status, inflammatory response, and clinical outcomes in elderly patients with gastric cancer.

Structural insights into the role of N-terminal integrity in PhoSL for core-fucosylated N-glycan recognition.

PhoSL (Pholiota squarrosa Lectin) has an exceptional binding affinity for biomolecules with core-fucosylated N-glycans. This modification involves the addition of fucose to the inner N-acetylglucosamine within the N-glycan structure and is known to influence many physiological processes. Nevertheless, the molecular interactions underlying high-affinity binding of native PhoSL to core-fucosylated N-glycans remain largely unknown. In this study, we devised a strategy to produce PhoSL with the essential structural characteristics of the native protein (n-PhoSL). To do so, a fusion protein was expressed in E. coli and purified. Then, enzymatic cleavage and incubation with glutathione were utilized to recapitulate the native primary structure and disulfide bonding pattern. Subsequently, we identified the residues crucial for n-PhoSL binding to core-fucosylated chitobiose (N2F) via NMR spectroscopy. Additionally, crystal structures were solved for both apo n-PhoSL and its N2F complex. These analyses suggested a pivotal role of the N-terminal amine in maintaining the integrity of the binding pocket and actively contributing to core-fucose recognition. In support of this idea, the inclusion of additional residues at the N-terminus considerably reduced binding affinity and PhoSL cytotoxicity toward breast cancer cells. Taken together, these findings can facilitate the utilization of PhoSL in basic research, diagnostics and therapeutic strategies.

Plasma SCUBE2 as a novel biomarker associates with survival outcomes in patients with sepsis-associated acute kidney injury.

BACKGROUND: The adverse effects of sepsis-associated acute kidney injury (SA-AKI) highlight the need for new biomarkers. Signal Peptide-Complement C1r/C1s, Uegf, Bmp1-Epidermal Growth Factor-like Domain-Containing Protein 2 (SCUBE2), important for angiogenesis and endothelial integrity, has been linked to increased mortality in models of lipopolysaccharide-induced lung injury. This research aimed to assess the utility of plasma SCUBE2 levels as a prognostic indicator for SA-AKI in intensive care unit (ICU) patients. METHODS: Between September 2020 and December 2022, our study enrolled ICU patients diagnosed with stage 3 SA-AKI. We collected demographic information, illness severity indices, and laboratory data, including plasma SCUBE2 and sepsis-triggered cytokine levels. We employed receiver operating characteristic curves and DeLong tests to assess the predictive accuracy for survival, Kaplan-Meier curves to evaluate the relative risk of death, and multivariate logistic regression to identify independent mortality predictors. RESULTS: Among the total of 200 participants, the survivors had significantly higher plasma SCUBE2 levels (115.9 ng/mL) compared to those who died (35.6 ng/mL). SCUBE2 levels showed a positive correlation with the anti-inflammatory cytokine IL-10 and a negative correlation with the APACHE II score, SOFA score, C-reactive protein, and monocyte chemoattractant protein-1. Multivariate analysis revealed that elevated SCUBE2 and IL-10 levels were independently protective against mortality, and associated with the most favorable 30-day survival outcomes. CONCLUSIONS: In ICU patients with stage 3 SA-AKI, lower plasma levels of SCUBE2 were correlated with elevated pro-inflammatory factors, which impacted survival outcomes. This suggests that SCUBE2 could be a potential biomarker for predicting prognosis in patients with SA-AKI.

[A project to reduce accidental falls among mentally ill residents in a long-term care facility].

BACKGROUND: Individuals with mental illness are highly vulnerable to personal health and safety threats. In recent years, the increasing incidence of accidental falls among residents of long-term care facilities has been attributed to aging, disease symptoms, and sedative drug effects. PURPOSE: This project aimed to reduce the fall incidence rate for mentally ill residents in our hospital from 0.0015% to 0.0012% in order to reduce patient injuries and avoid the long-term health consequences of these injuries. RESOLUTION: This project was conducted between January 1st, 2011 and December 31st, 2011. Our approach included direct observation, literature review, meeting discussions, and data compilation. The intervention composed four facets: (1) Staff: providing education and training skills to prevent patient falls; (2) residents: enhancing patient motivation to keep physically fit and assess medication side effects; (3) environment: increasing living condition safety; (4) policy: replacing defective equipment, performing equipment checks on schedule, and managing a fall-prevention program. RESULTS: The post-intervention fall incidence rate for mentally ill residents was 0.0007%, which was significantly better than our target. CONCLUSIONS: We reviewed plans and improved the fall-prevention strategy for mentally ill residents of long-term care facilities. This project provides a reference for care program planners and administrators.

Co-delivery of a tumor microenvironment-responsive disulfiram prodrug and CuO2 nanoparticles for efficient cancer treatment.

Disulfiram (DSF) has been used as a hangover drug for more than seven decades and was found to have potential in cancer treatment, especially mediated by copper. However, the uncoordinated delivery of disulfiram with copper and the instability of disulfiram limit its further applications. Herein, we synthesize a DSF prodrug using a simple strategy that could be activated in a specific tumor microenvironment. Poly amino acids are used as a platform to bind the DSF prodrug through the B-N interaction and encapsulate CuO2 nanoparticles (NPs), obtaining a functional nanoplatform Cu@P-B. In the acidic tumor microenvironment, the loaded CuO2 NPs will produce Cu2+ and cause oxidative stress in cells. At the same time, the increased reactive oxygen species (ROS) will accelerate the release and activation of the DSF prodrug and further chelate the released Cu2+ to produce the noxious copper diethyldithiocarbamate complex, which causes cell apoptosis effectively. Cytotoxicity tests show that the DSF prodrug could effectively kill cancer cells with only a small amount of Cu2+ (0.18 µg mL-1), inhibiting the migration and invasion of tumor cells. In vitro and in vivo experiments have demonstrated that this functional nanoplatform could kill tumor cells effectively with limited toxic side effects, showing a new perspective in DSF prodrug design and cancer treatment.