Enteric coronavirus nsp2 is a virulence determinant that recruits NBR1 for autophagic targeting of TBK1 to diminish the innate immune response.

Non-structural protein 2 (nsp2) exists in all coronaviruses (CoVs), while its primary function in viral pathogenicity, is largely unclear. One such enteric CoV, porcine epidemic diarrhea virus (PEDV), causes high mortality in neonatal piglets worldwide. To determine the biological role of nsp2, we generated a PEDV mutant containing a complete nsp2 deletion (rPEDV-Δnsp2) from a highly pathogenic strain by reverse genetics, showing that nsp2 was dispensable for PEDV infection, while its deficiency reduced viral replication in vitro. Intriguingly, rPEDV-Δnsp2 was entirely avirulent in vivo, with significantly increased productions of IFNB (interferon beta) and IFN-stimulated genes (ISGs) in various intestinal tissues of challenged newborn piglets. Notably, nsp2 targets and degrades TBK1 (TANK binding kinase 1), the critical kinase in the innate immune response. Mechanistically, nsp2 induced the macroautophagy/autophagy process and recruited a selective autophagic receptor, NBR1 (NBR1 autophagy cargo receptor). NBR1 subsequently facilitated the K48-linked ubiquitination of TBK1 and delivered it for autophagosome-mediated degradation. Accordingly, the replication of rPEDV-Δnsp2 CoV was restrained by reduced autophagy and excess productions of type I IFNs and ISGs. Our data collectively define enteric CoV nsp2 as a novel virulence determinant, propose a crucial role of nsp2 in diminishing innate antiviral immunity by targeting TBK1 for NBR1-mediated selective autophagy, and pave the way to develop a new type of nsp2-based attenuated PEDV vaccine. The study also provides new insights into the prevention and treatment of other pathogenic CoVs.Abbreviations: 3-MA: 3-methyladenine; Baf A1: bafilomycin A1; CoV: coronavirus; CQ: chloroquine; dpi: days post-inoculation; DMVs: double-membrane vesicles; GABARAP: GABA type A receptor-associated protein; GFP: green fluorescent protein; GIGYF2: GRB10 interacting GYF protein 2; hpi: hours post-infection; IFA: immunofluorescence assay; IFIH1: interferon induced with helicase C domain 1; IFIT2: interferon induced protein with tetratricopeptide repeats 2; IFITM1: interferon induced transmembrane protein 1; IFNB: interferon beta; IRF3: interferon regulatory factor 3; ISGs: interferon-stimulated genes; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; NBR1: NBR1 autophagy cargo receptor; nsp2: non-structural protein 2; OAS1: 2'-5'-oligoadenylate synthetase 1; PEDV: porcine epidemic diarrhea virus; PRRs: pattern recognition receptors; RIGI: RNA sensor RIG-I; RT-qPCR: reverse transcription quantitative polymerase chain reaction; SQSTM1: sequestosome 1; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; VSV: vesicular stomatitis virus.

Efficient generation of cloned cats with altered coat colour by editing of the KIT gene.

Coat colour largely determines the market demand for several cat breeds. The KIT proto-oncogene (KIT) gene is a key gene controlling melanoblast differentiation and melanogenesis. KIT mutations usually cause varied changes in coat colour in mammalian species. In this study, we used a pair of single-guide RNAs (sgRNAs) to delete exon 17 of KIT in somatic cells isolated from two different Chinese Li Hua feline foetuses. Edited cells were used as donor nuclei for somatic cell nuclear transfer (SCNT) to generate cloned embryos presenting an average cleavage rate exceeding 85%, and an average blastocyst formation rate exceeding 9.5%. 131 cloned embryos were transplanted into four surrogates, and all surrogates carried their pregnancies to term, and delivered 4.58% (6/131) alive cloned kittens, with 1.53% (2/131) being KIT-edited heterozygotes (KITD17/+). The KITD17/+ cats presented an obvious darkness reduction in the mackerel tabby coat. Immunohistochemical analysis (IHC) of skin tissues indicated impaired proliferation and differentiation of melanoblasts caused by the lack of exon17 in feline KIT. To our knowledge, this is the first report on coat colour modification of cats through gene editing. The findings could facilitate further understanding of the regulatory role of KIT on feline coat colour and provide a basis for the breeding of cats with commercially desired coat colour.

Vonoprazan is Not Inferior to Proton Pump Inhibitors in Bismuth-containing Quadruple Therapy for Helicobacter pylori Eradication: A Meta-analysis of 10 Studies From East Asia.

OBJECTIVE: To investigate the efficacy and safety of vonoprazan based bismuth-containing quadruple therapy (VBCQ) in eradicating Helicobacter pylori (Hp). MATERIALS AND METHODS: The VBCQ and the proton pump inhibitor-based bismuth-containing quadruple regimen (PBCQ) were compared by retrieving relevant studies in Pubmed, Embase, Cochrane Library, CNKI, and Wanfang data. Combined analysis was performed with risk ratio (RR) and 95% CI as effect values. RESULTS: A total of 10 studies were enrolled, including 7 randomized controlled trials and 3 cohort studies. In intention-to-treat analysis, the eradication rate of VBCQ (89.24%, 1103/1236) was significantly higher than that of PBCQ (84.03%, 1021/1215), with RR = 1.06 (95% CI: 1.03~1.10). In per-protocol analysis, the eradication rates of VBCQ and PBCQ were 92.94% (895/963) and 87.82% (829/944), respectively, with a significant difference (RR = 1.06, 95% CI: 1.03~1.09). Subgroup analysis of study design types shared similar results. VBCQ and PBCQ showed an incidence of adverse reactions of 37.30% (304/815) and 34.94% (282/807), respectively. Significant differences were not found between the two groups (RR = 1.07, 95% CI: 0.96-1.19), nor in subgroup analysis. The good compliance rates in VBCQ and PBCQ groups were 94.32% (216/229) and 95.13% (215/226), respectively, with no significant difference (RR = 0.99, 95% CI: 0.95~1.04). CONCLUSION: VBCQ has a higher eradication rate on Hp than PBCQ, while its adverse reactions and compliance are similar to PBCQ. However, we conservatively believe that in Hp eradication, the VBCQ is not inferior to PBCQ because of the small absolute difference.

Construction of the single-diamond-structured titania scaffold-Recreation of the holy grail photonic structure.

As one of the most stunning biological nanostructures, the single-diamond (SD) surface discovered in beetles and weevils exoskeletons possesses the widest complete photonic bandgap known to date and is renowned as the "holy grail" of photonic materials. However, the synthesis of SD is difficult due to its thermodynamical instability compared to the energetically favoured bicontinuous double diamond and other easily formed lattices; thus, the artificial fabrication of SD has long been a formidable challenge. Herein, we report a bottom-up approach to fabricate SD titania networks via a one-pot cooperative assembly scenario employing the diblock copolymer poly(ethylene oxide)-block-polystyrene as a soft template and titanium diisopropoxide bis(acetylacetonate) as an inorganic precursor in a mixed solvent, in which the SD scaffold was obtained by kinetically controlled nucleation and growth in the skeletal channels of the diamond minimal surface formed by the polymer matrix. Electron crystallography investigations revealed the formation of tetrahedrally connected SD frameworks with the space group Fd [Formula: see text] m in a polycrystalline anatase form. A photonic bandgap calculation showed that the resulting SD structure has a wide and complete bandgap. This work solves the complex synthetic enigmas and offers a frontier in hyperbolic surfaces, biorelevant materials, next-generation optical devices, etc.

Lithium chloride promotes mesenchymal-epithelial transition in murine cutaneous wound healing via inhibiting CXCL9 and IGF2.

Cutaneous wound healing is a challenge in plastic and reconstructive surgery. In theory, cells undergoing mesenchymal transition will achieve re-epithelialization through mesenchymal-epithelial transition at the end of wound healing. But in fact, some pathological stimuli will inhibit this biological process and result in scar formation. If mesenchymal-epithelial transition can be activated at the corresponding stage, the ideal wound healing may be accomplished. Two in vivo skin defect mouse models and dermal-derived mesenchymal cells were used to evaluate the effect of lithium chloride in wound healing. The mesenchymal-epithelial transition was detected by immunohistochemistry staining. In vivo, differentially expressed genes were analysed by transcriptome analyses and the subsequent testing was carried out. We found that lithium chloride could promote murine cutaneous wound healing and facilitate mesenchymal-epithelial transition in vivo and in vitro. In lithium chloride group, scar area was smaller and the collagen fibres are also orderly arranged. The genes related to mesenchyme were downregulated and epithelial mark genes were activated after intervention. Moreover, transcriptome analyses suggested that this effect might be related to the inhibition of CXCL9 and IGF2, subsequent assays demonstrated it. Lithium chloride can promote mesenchymal-epithelial transition via downregulating CXCL9 and IGF2 in murine cutaneous wound healing, the expression of IGF2 is regulated by ß-catenin. It may be a potential promising therapeutic drug for alleviating postoperative scar and promoting re-epithelialization in future.

Effects of soaking glutinous sorghum grains on physicochemical properties of starch.

Glutinous sorghum grains were soaked (60-80 °C, 2-8 h) to explore the effects of soaking, an essential step in industrial processing of brewing, on starch. As the soaking temperature increased, the peak viscosity and crystallinity of starch gradually decreased, while the enzymatic hydrolysis rate and storage modulus first increased and then decreased. At 70 °C, the content of amylose, the enzymatic hydrolysis rate of starch, and the final viscosity first increase and then decrease with the increase of soaking time, reaching their maximum at 6 h, increased by 53.1 %, 11.0 %, and 10.4 %, respectively, as compared with the non-soaked sample. At 80 °C (4 h), the laser confocal microscopy images showed a network structure formed between the denatured protein chains and the leached-out amylose chains. The molecular weights of starch before and after soaking were all in the range of 3.82-8.98 × 107 g/mol. Since 70 °C is lower than that of starch gelatinization and protein denaturation, when soaking for 6 h, the enzymatic hydrolysis rate of starch is the highest, and the growth of miscellaneous bacteria is inhibited, which is beneficial for subsequent processing technology. The result provides a theoretical basis for the intelligent control of glutinous sorghum brewing.

Metabolic score for insulin resistance predicts major adverse cardiovascular event in premature coronary artery disease.

BACKGROUND: The Metabolic Score for Insulin Resistance (METS-IR) index serves as a simple surrogate marker for insulin resistance (IR) and is associated with the presence and severity of coronary artery disease (CAD). However, the prognostic significance of METS-IR in patients with premature CAD remains unclear. This study aims to investigate the prognostic value of METS-IR in premature CAD. METHODS: This retrospective study included 582 patients diagnosed with premature CAD between December 2012 and July 2019. The median follow-up duration was 63 months (interquartile range, 44-81 months). The primary endpoint was Major Adverse Cardiovascular Events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction (MI), repeat coronary artery revascularization, and non-fatal stroke. RESULTS: Patients with MACE had significantly higher METS-IR levels than those without MACE (44.88±8.11 vs. 41.68±6.87, p<0.001). Kaplan-Meier survival curves based on METS-IR tertiles demonstrated a statistically significant difference (log-rank test, p<0.001). In the fully adjusted model, the Hazard Ratio (95% CI) for MACE was 1.41 (1.16-1.72) per SD increase in METS-IR, and the P for trend based on METS-IR tertiles was 0.001 for MACE. Time-dependent Receiver Operator Characteristic (ROC) analysis of METS-IR yielded an Area Under the Curve (AUC) of 0.74 at 2 years, 0.69 at 4 years, and 0.63 at 6 years. CONCLUSIONS: METS-IR serves as a reliable prognostic predictor of MACE in patients with premature CAD. Therefore, METS-IR may be considered a novel, cost-effective, and dependable indicator for risk stratification and early intervention in premature CAD.

Macleaya cordata extract improves growth performance, immune responses and anti-inflammatory capacity in neonatal piglets.

Macleaya cordata was a kind of traditional herbal medicine, which may a potential substitute for antibiotics. However, the effects of Macleaya cordata on neonatal piglets have rarely been reported. In this study, three groups were designed, including normal saline (Control group, CON), 8 mg/mL Macleaya cordata extract (MCE group, MCE) and 5 mg/mL Chlortetracycline Hydrochloride (CCH group, CCH), to investigate the effects of MCE on growth performance, blood parameters, inflammatory cytokines, regenerating islet-derived 3 gamma (REG3γ) expression and the transcriptomes of neonatal piglets. The results showed that, compared with the control group, MCE significantly increased the average daily gain (p < 0.01); spleen index (p < 0.05) contents of IL-10, TGF-ß, IgG in serum and sIgA in the ileum mucus of neonatal piglets at 7 d and 21 d (p < 0.01). The diarrhoea incidence and serum TNF-α and IFN-γ contents of neonatal piglets at 7 d and 21 d were significantly decreased (p < 0.01). In addition, MCE significantly increased the mRNA expression of TGF-ß, IL-10, and REG3γ (p < 0.01) and significantly decreased the mRNA expression of IL-33, TNF-α and IFN-γ in the ileal mucosa of neonatal piglets at 21 d (p < 0.01). The differentially expressed genes and the signal pathways, related to cytokine generation and regulation, immunoregulation and inflammation were identified. In conclusion, MCE can significantly improve growth performance, reduce diarrhoea incidence, relieve inflammation, improve immune function, and improve disease resistance in neonatal piglets. MCE can be used as a potential substitute for antibiotics in neonatal piglets.

Adhesion Energy-Assisted Low Contact Thermal Resistance Epoxy Resin-Based Composite.

Although intense efforts have been devoted to the development of thermally conductive epoxy resin composites, most previous works ignore the importance of the contact thermal resistance between epoxy resin composites and mating surfaces. Here, we report on epoxy resin/hexagonal boron nitride (h-BN) composites, which show low contact thermal resistance with the contacting surface by tuning adhesion energy. We found that adhesion energy increases with increasing the ratio of soybean-based epoxy resin/amino silicone oil and h-BN contents. The adhesion energy has a negative correlation with the contact thermal resistance; that is, enhancing the adhesion energy will lead to reduced contact thermal resistance. The contact thermal conductance increases with the h-BN contents and is low to 0.025 mm2·K/W for the epoxy resin/60 wt % h-BN composites, which is consistent with the theoretically calculated value. By investigating the wettability and chain dynamics of the epoxy resin/h-BN composites, we confirm that the low contact thermal resistance stems from the increased intermolecular interaction between the epoxy resin chains. The present study provides a practical approach for the development of epoxy resin composites with enhanced thermal conductivity and reduced contact thermal resistance, aiming for effective thermal management of electronics.

The Impact of FBN1-α5ß1 Axis in Fibro/Adipogenic Progenitor Cells (FAPCD9-) on Intramuscular Fat Content in Pigs.

Intramuscular fat (IMF) plays a crucial role in enhancing meat quality, enriching meat flavor, and overall improving palatability. In this study, Single-cell RNA sequencing was employed to analyze the longissimus dorsi (LD) obtained from Guangdong small-ear spotted pigs (GDSS, with high IMF) and Yorkshire pigs (YK, with low IMF). GDSS had significantly more Fibro/Adipogenic Progenitor (FAPs), in which the CD9 negative FAPs (FAPCD9-) having adipogenic potential, as demonstrated by in vitro assays using cells originated from mouse muscle. On the other hand, Yorkshire had more fibro-inflammatory progenitors (FIPs, marked with FAPCD9+), presenting higher expression of the FBN1-Integrin α5ß1. FBN1-Integrin α5ß1 could inhibit insulin signaling in FAPCD9-, suppressing adipogenic differentiation. Our results demonstrated that fat-type pigs possess a greater number of FAPCD9-, which are the exclusive cells in muscle capable of differentiating into adipocytes. Moreover, lean-type pigs exhibit higher expression of FBN1-Integrin α5ß1 axis, which inhibits adipocyte differentiation. These results appropriately explain the observed higher IMF content in fat-type pigs.

Effects of clarithromycin exposure on the growth of Microcystis aeruginosa and the production of algal dissolved organic matter.

Antibiotics are commonly found in the aquatic environment, which can affect microbial community compositions and activities, and even have potential adverse impacts on human and ecosystem health. The current understanding of the effects of antibiotics on microalgae growth and algal dissolved organic matter (DOM) remains indistinct. To understand the toxic effects of antibiotics on the microalgae, Microcystis aeruginosa was exposed to clarithromycin (CLA) in this study. Cell density determination, chlorophyll content determination, and organic spectrum analysis were conducted to show the effect of CLA exposure on the growth, photosynthetic activity, and organic metabolic processes of Microcystis aeruginosa. The findings revealed that the physiological status of algae could be significantly influenced by CLA exposure in aquatic environments. Specifically, exposure to 1 µg/L CLA stimulated the growth and photosynthetic activity of algal cells. Conversely, CLA above 10 µg/L led to the inhibition of algal cell growth and photosynthesis. Notably, the inhibitory effects intensified with the increasing concentration of CLA. The molecular weight of DOM produced by Microcystis aeruginosa increased when exposed to CLA. Under the exposure of 60 µg/L CLA, a large number of algal cells ruptured and died, and the intracellular organic matter was released into the algal liquid. This resulted in an increase in high molecular weight substances and soluble microbial-like products in the DOM. Exposure to 1 and 10 µg/L CLA stimulated Microcystis aeruginosa to produce more humic acid-like substances, which may be a defense mechanism against CLA. The results were useful for assessing the effects of antibiotic pollution on the stability of the microalgae population and endogenous DOM characteristics in aquatic ecosystems.

Differentiation of Type 17 Mucosal-Associated Invariant T Cells in Circulation Contributes to the Severity of Sepsis.

Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RAR-related orphan receptor γt in patients with sepsis. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA-sequencing analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in patients with sepsis. Cell-culture experiments demonstrated that phosphoinositide 3-kinase-LDHA signaling was required for RAR-related orphan receptor γt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 cells in sepsis. In summary, this study reveals a new role of circulating MAIT17 in promoting sepsis severity and suggests the phosphoinositide 3-kinase-LDHA signaling as a driving force in MAIT17 responses.

Strain engineering of Bacillus coagulans with high osmotic pressure tolerance for effective L-lactic acid production from sweet sorghum juice under unsterile conditions.

Open unsterile fermentation of the low-cost non-food crop, sweet sorghum, is an economically feasible lactic acid biosynthesis process. However, hyperosmotic stress inhibits microbial metabolism and lactic acid biosynthesis, and engineering strains with high osmotic tolerance is challenging. Herein, heavy ion mutagenesis combined with osmotic pressure enrichment was used to engineer a hyperosmotic-tolerant Bacillus coagulans for L-lactic acid production. The engineered strain had higher osmotic pressure tolerance, when compared with the parental strain, primarily owing to its improved properties such as cell viability, cellular antioxidant capacity, and NADH supply. In a pilot-scale open unsterile fermentation using sweet sorghum juice as a feedstock, the engineered strain produced 94 g/L L-lactic acid with a yield of 91 % and productivity of 6.7 g/L/h, and optical purity of L-lactic acid at the end of fermentation was 99.8 %. In short, this study provided effective and low-cost approach to produce polymer-grade L-lactic acid.

Light-induced giant enhancement of nonreciprocal transport at KTaO3-based interfaces.

Nonlinear transport is a unique functionality of noncentrosymmetric systems, which reflects profound physics, such as spin-orbit interaction, superconductivity and band geometry. However, it remains highly challenging to enhance the nonreciprocal transport for promising rectification devices. Here, we observe a light-induced giant enhancement of nonreciprocal transport at the superconducting and epitaxial CaZrO3/KTaO3 (111) interfaces. The nonreciprocal transport coefficient undergoes a giant increase with three orders of magnitude up to 105 A-1 T-1. Furthermore, a strong Rashba spin-orbit coupling effective field of 14.7 T is achieved with abundant high-mobility photocarriers under ultraviolet illumination, which accounts for the giant enhancement of nonreciprocal transport coefficient. Our first-principles calculations further disclose the stronger Rashba spin-orbit coupling strength and the longer relaxation time in the photocarrier excitation process, bridging the light-property quantitative relationship. Our work provides an alternative pathway to boost nonreciprocal transport in noncentrosymmetric systems and facilitates the promising applications in opto-rectification devices and spin-orbitronic devices.

hsa_circ_0007919 promotes pancreatic cancer metastasis by modulating Sp1-mediated THBS1 transcription.

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC.

Encoding Genetic Circuits with DNA Barcodes Paves the Way for High-Throughput Profiling of Dose-Response Curves of Metabolite Biosensors.

Metabolite biosensors, through which the intracellular metabolite concentrations could be converted to changes in gene expression, are widely used in a variety of applications according to the different output signals. However, it remains challenging to fine-tune the dose-response relationships of biosensors to meet the needs of various scenarios. On the other hand, the short read length of next-generation sequencing (NGS) has greatly limited the design capability of sequence libraries. To address these issues, we describe a DNA trackable assembly method, coupled with fluorescence-activated cell sorting and NGS (Sort-Seq), to achieve the characterization of dose-response curves in a massively parallel manner. As a proof of the concept, we constructed a malonyl-CoA biosensor library containing 5184 combinations with six levels of transcription factor dosage, four different operator positions, and 216 possible upstream enhancer sequence (UAS) designs in Saccharomyces cerevisiae BY4700. By using Sort-Seq and machine learning approach, we obtained comprehensive dose-response relationships of the combinatorial sequence space. Therefore, our pipeline provides a platform for the design, tuning, and profiling of biosensor response curves and shows great potential to facilitate the rational design of genetic circuits.

Timely use of Bakri intrauterine balloon tamponade contributes to the effectiveness in controlling severe postpartum hemorrhage.

The aim of the present study was to explore the effectiveness of Bakri intrauterine balloon tamponade (IUBT) in treating severe postpartum hemorrhage (SPPH). A cohort of 198 women with SPPH using IUBT were retrospectively selected. The baseline and maternal outcome characteristics were examined. The results demonstrated that women with SPPH had a high proportion of placenta accrete (53.0%). Bakri IUBT demonstrated a global effectiveness of 84.5% in SPPH treatment, accounting for 82.9% in women with placenta accrete. Compared with women with Bakri failure, women who experienced Bakri success had reduced rates of less use of pre-/post-IUBT intervention, blood transfusion, lower genital tract trauma, estimated blood loss (EBL), and a longer indwelling duration (P<0.05). Logistic regression revealed that the pre-IUBT intervention (OR=3.910; 95% CI: 1.684-9.079; P=0.002) was positively associated with hemostasis success, while lower genital tract trauma was negatively associated with Bakri success (OR=0.091; 95% CI: 0.009-0.894; P=0.040). Moreover, women diagnosed with placenta accrete underwent a greater number of transabdominal placed Bakri IUBT and pre-IUBT interventions than those without placenta accrete (P<0.05). No significant differences were observed in Bakri success, total EBL, pre-/post-IUBT EBL, infused volume of IUBT, IUBT indwelling duration, even the rate of hemostasis, lower genital tract trauma, blood transfusion, post-IUBT intervention, and puerperal fever between women with and without placenta accrete (P>0.05). In conclusion, placenta accrete may be the leading cause of SPPH. Bakri IUBT is an effective and safe measure for SPPH. Pre-IUBT intervention may be predictive of Bakri's success. The timely use of IUBT during labor may mitigate the impact of risk factors identified on PPH.

An activatable fluorescent-photoacoustic dual-modal probe for highly sensitive imaging of nitroxyl in vivo.

Nitroxyl (HNO) plays a vital role in various biological functions and pharmacological activities, so the development of an excellent near-infrared fluorescent (NIRF) and photoacoustic (PA) dual-modality probe is crucial for understanding HNO-related physiological and pathological progression. Herein, we proposed and synthesized a novel NIRF/PA dual probe (QL-HNO) by substituting an indole with quinolinium in hemicyanine for the sensitive detection of exogenous and endogenous HNO in vivo. The designed probe showed the highest sensitivity in NIRF mode and a desirable PA signal-to-noise ratio for HNO detection in vitro and was further applied for NIRF/PA dual-modal imaging of HNO with high contrast in living cells and tumor-bearing animals. Based on the excellent performance of QL-HNO, we believe that this study provides a promising molecular tool for further understanding of HNO-related physiological and pathological progression.

Novel prognostic biomarker TBC1D1 is associated with immunotherapy resistance in gliomas.

Background: Glioma, an aggressive brain tumor, poses a challenge in understanding the mechanisms of treatment resistance, despite promising results from immunotherapy. Methods: We identified genes associated with immunotherapy resistance through an analysis of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. Subsequently, qRT-PCR and western blot analyses were conducted to measure the mRNA and protein levels of TBC1 Domain Family Member 1 (TBC1D1), respectively. Additionally, Gene Set Enrichment Analysis (GSEA) was employed to reveal relevant signaling pathways, and the expression of TBC1D1 in immune cells was analyzed using single-cell RNA sequencing (scRNA-seq) data from GEO database. Tumor Immune Dysfunction and Exclusion (TIDE) database was utilized to assess T-cell function, while Tumor Immunotherapy Gene Expression Resource (TIGER) database was employed to evaluate immunotherapy resistance in relation to TBC1D1. Furthermore, the predictive performance of molecules on prognosis was assessed using Kaplan-Meier plots, nomograms, and ROC curves. Results: The levels of TBC1D1 were significantly elevated in tumor tissue from glioma patients. Furthermore, high TBC1D1 expression was observed in macrophages compared to other cells, which negatively impacted T cell function, impaired immunotherapy response, promoted treatment tolerance, and led to poor prognosis. Inhibition of TBC1D1 was found to potentially synergistically enhance the efficacy of immunotherapy and prolong the survival of cancer patients with gliomas. Conclusion: Heightened expression of TBC1D1 may facilitate an immunosuppressive microenvironment and predict a poor prognosis. Blocking TBC1D1 could minimize immunotherapy resistance in cancer patients with gliomas.

Individual stigma in people with severe mental illness: Associations with public stigma, psychological capital, cognitive appraisal and coping orientations.

INTRODUCTION: The reason why some people with severe mental illness (SMI) maintain positive self-identity, while some are affected by the stigmatized environment is unclear. AIMS: To describe the status of individual stigma and explore the relationship between self-stigma, stigma resistance and related variables in people with SMI. METHODS: A cross-sectional study was conducted from April 2021 to March 2022. The Chinese version of Internalized Stigma of Mental Illness Scale and Stigma Resistance Scale were used to assess individual stigma. Perceived public stigma, psychological capital, stigma stress appraisal and coping orientations were also measured by scales. Data was provided by 422 patients with schizophrenia or bipolar disorder, from one psychiatric hospital and four community healthcare centers in China. A structural equation model was applied for analysis. RESULTS: The total mean scores of self-stigma and stigma resistance were (2.06 ± 0.65), and (3.95 ± 0.84). Perceived public stigma was the primary condition for constructing individual stigma, which indirectly affected self-stigma (ß = 0.268) and stigma resistance (ß = -0.145). Stigma stress appraisal mediated the transformation of public stigma into individual, which had direct and indirect effects on self-stigma (ß = 0.417, 0.166), and an indirect effect on stigma resistance (ß = -0.374). Secrecy positively affected self-stigma (ß = 0.117), while positive coping positively affected stigma resistance (ß = 0.380). Psychological capital significantly directly impacted individual stigma. CONCLUSIONS: Findings highlighted how public stigma determines the degree to which patients with SMI deal with stigma stress appraisal, and how this influences individuals. Anti-stigma programs and interventions to improve individuals' psychological capital and coping capabilities should be emphasized.