CREB3 suppresses hepatocellular carcinoma progression by depressing AKT signaling through competitively binding with insulin receptor and transcriptionally activating RNA-binding motif protein 38.

cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA-binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38.

Rapid discrimination of African swine fever virus nucleic acid and virions using BenzoNuclease.

African swine fever (ASF) is an acute and severe infectious disease caused by the African Swine Fever Virus (ASFV). ASFV exhibits significant resistance and stability in the environment, which, coupled with its double-stranded DNA and large genome, predisposes it to contaminate laboratory samples. This characteristic can lead to false-positive results in swine farm settings even days after disinfection, as detectable through polymerase chain reaction (PCR) or real-time fluorescent quantitative PCR (qPCR) assays. To meet the demand for efficient clinical methods capable of discriminating between ASFV nucleic acid and ASFV virions, this study aims to ascertain the efficacy of the nuclease "BenzoNuclease" in distinguishing ASFV nucleic acid (ASFV-DNA) from ASFV virions. BenzoNuclease is a versatile nucleic acid enzyme with the capacity to degrade nearly all forms of DNA and RNA. Initially, this research established a highly sensitive general PCR detection method for ASFV. Subsequently, a positive control was constructed using the M13 bacteriophage to substitute for active ASFV, facilitating the development of an improved qPCR method. It is important to note that common disinfectants have the potential to deactivate BenzoNuclease. However, in an environment simulating actual production applications, residual disinfectants do not interfere with the enzymatic efficacy of BenzoNuclease, thus not affecting the detection capabilities of this method. Positive clinical samples from pig farms, upon testing with the improved method, revealed that three samples were positive, indicating the presence of viral particles, while the remaining samples were negative, indicating the presence of nucleic acids. This provides an additional new option for sample testing in pig farms.

One-to-Nine Single Spectroscopic Intelligent Probe for Risk Assessment of Multiple Metals in Drinking Water.

26% of the world's population lacks access to clean drinking water; clean water and sanitation are major global challenges highlighted by the UN Sustainable Development Goals, indicating water security in public water systems is at stake today. Water monitoring using precise instruments by skilled operators is one of the most promising solutions. Despite decades of research, the professionalism-convenience trade-off when monitoring ubiquitous metal ions remains the major challenge for public water safety. Thus, to overcome these disadvantages, an easy-to-use and highly sensitive visual method is desirable. Herein, an innovative strategy for one-to-nine metal detection is proposed, in which a novel thiourea spectroscopic probe with high 9-metal affinity is synthesized, acting as "one", and is detected based on the 9 metal-thiourea complexes within portable spectrometers in the public water field; this is accomplished by nonspecialized personnel as is also required. During the processing of multimetal analysis, issues arise due to signal overlap and reproducibility problems, leading to constrained sensitivity. In this innovative endeavor, machine learning (ML) algorithms were employed to extract key features from the composite spectral signature, addressing multipeak overlap, and completing the detection within 30-300 s, thus achieving a detection limit of 0.01 mg/L and meeting established conventional water quality standards. This method provides a convenient approach for public drinking water safety testing.

MnO2 Nanoparticles Decorated PEDOT:PSS for High Performance Stretchable and Transparent Supercapacitors.

With the swift advancement of wearable electronics and artificial intelligence, the integration of electronic devices with the human body has advanced significantly, leading to enhanced real-time health monitoring and remote disease diagnosis. Despite progress in developing stretchable materials with skin-like mechanical properties, there remains a need for materials that also exhibit high optical transparency. Supercapacitors, as promising energy storage devices, offer advantages such as portability, long cycle life, and rapid charge/discharge rates, but achieving high capacity, stretchability, and transparency simultaneously remains challenging. This study combines the stretchable, transparent polymer PEDOT:PSS with MnO2 nanoparticles to develop high-performance, stretchable, and transparent supercapacitors. PEDOT:PSS films were deposited on a PDMS substrate using a spin-coating method, followed by electrochemical deposition of MnO2 nanoparticles. This method ensured that the nanosized MnO2 particles were uniformly distributed, maintaining the transparency and stretchability of PEDOT:PSS. The resulting PEDOT:PSS/MnO2 nanoparticle electrodes were gathered into a symmetric device using a LiCl/PVA gel electrolyte, achieving an areal capacitance of 1.14 mF cm-2 at 71.2% transparency and maintaining 89.92% capacitance after 5000 cycles of 20% strain. This work presents a scalable and economical technique to manufacturing supercapacitors that combine high capacity, transparency, and mechanical stretchability, suggesting potential applications in wearable electronics.

HGF ameliorates cardiomyocyte apoptosis and inflammatory response in sepsis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.

OBJECTIVE: This study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). METHODS: Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. RESULTS: The outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. CONCLUSION: HGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.

In situ imaging of intracellular miRNAs in tumour cells by branched hybridisation chain reaction.

The ability to visualise microRNA in situ is crucial for studying microRNAs, their microRNA-associated biological functions and disease diagnosis. Traditional fluorescence in situ hybridisation methods based on paraformaldehyde fixation of microRNAs suffer from release of microRNAs from cells, which limits the sensitivity of in situ hybridisation, making them unsuitable for the detection of small, low-abundance microRNAs. To reduce the loss, microRNAs were covalently cross-linked to proteins within cells by combining EDC and paraformaldehyde, and the target microRNA was used as the initiator chain for a branched hybridisation chain reaction to detect microRNA expression levels in situ. A simplified branched hybridisation chain reaction can be realised by coupling two hybridisation chain reaction circuits with a hairpin linker. Upon forming the primary hybridisation chain reaction product with extended sequence, this sequence reacts with the linker hairpin H3 to release the initiator sequence, resulting in the formation of numerous dendritic branched hybridisation chain reaction products. Imaging results show that this technique can detect microRNAs with high sensitivity and selectivity at both the single-cell and single-molecule levels. Compared with the traditional fluorescence in situ hybridisation technique, this method greatly improves the sensitivity and image resolution of in situ imaging detection. Therefore, we believe that the target-initiated branched hybridisation chain reaction based in situ detection method provides a reliable assay platform for analysing disease-related microRNA expression.

African swine fever virus pB475L evades host antiviral innate immunity via targeting STAT2 to inhibit IFN-I signaling.

African swine fever virus (ASFV) causes severe disease in domestic pigs and wild boars, seriously threatening the development of the global pig industry. Type I interferon (IFN-I) is an important component of innate immunity, inducing the transcription and expression of antiviral cytokines by activating Janus-activated kinase-signal transducer and activator of transcription (STAT). However, the underlying molecular mechanisms by which ASFV antagonizes IFN-I signaling have not been fully elucidated. Therefore, using coimmunoprecipitation, confocal microscopy, and dual luciferase reporter assay methods, we investigated these mechanisms and identified a novel ASFV immunosuppressive protein, pB475L, which interacts with the C-terminal domain of STAT2. Consequently, pB475L inhibited IFN-I signaling by inhibiting STAT1 and STAT2 heterodimerization and nuclear translocation. Furthermore, we constructed an ASFV-B475L7PM mutant strain by homologous recombination, finding that ASFV-B475L7PM attenuated the inhibitory effects on IFN-I signaling compared to ASFV-WT. In summary, this study reveals a new mechanism by which ASFV impairs host innate immunity.

Subcellular localization of viral proteins after porcine epidemic diarrhea virus infection and their roles in the viral life cycle.

Porcine epidemic diarrhea virus (PEDV) is one of the most devastating diseases affecting the pig industry globally. Due to the emergence of novel strains, no effective vaccines are available for prevention and control. Investigating the pathogenic mechanisms of PEDV may provide insights for creating clinical interventions. This study constructed and expressed eukaryotic expression vectors containing PEDV proteins (except NSP11) with a 3' HA tag in Vero cells. The subcellular localization of PEDV proteins was examined using endogenous protein antibodies to investigate their involvement in the viral life cycle, including endocytosis, intracellular trafficking, genome replication, energy metabolism, budding, and release. We systematically analyzed the potential roles of all PEDV viral proteins in the virus life cycle. We found that the endosome sorting complex required for transport (ESCRT) machinery may be involved in the replication and budding processes of PEDV. Our study provides insight into the molecular mechanisms underlying PEDV infection. IMPORTANCE: The global swine industry has suffered immense losses due to the spread of PEDV. Currently, there are no effective vaccines available for clinical protection. Exploring the pathogenic mechanisms of PEDV may provide valuable insights for clinical interventions. This study investigated the involvement of viral proteins in various stages of the PEDV lifecycle in the state of viral infection and identified several previously unreported interactions between viral and host proteins. These findings contribute to a better understanding of the pathogenic mechanisms underlying PEDV infection and may serve as a basis for further research and development of therapeutic strategies.

Oxidative stress induces extracellular vesicle release by upregulation of HEXB to facilitate tumour growth in experimental hepatocellular carcinoma.

Extracellular vesicles (EVs) play a crucial role in triggering tumour-aggressive behaviours. However, the energetic process by which tumour cells produce EVs remains poorly understood. Here, we demonstrate the involvement of ß-hexosaminidase B (HEXB) in mediating EV release in response to oxidative stress, thereby promoting the development of hepatocellular carcinoma (HCC). Mechanistically, reactive oxygen species (ROS) stimulate the nuclear translocation of transcription factor EB (TFEB), leading to the upregulation of both HEXB and its antisense lncRNA HEXB-AS. HEXB-AS can bind HEXB to form a protein/RNA complex, which elevates the protein stability of HEXB. The stabilized HEXB interacts with lysosome-associated membrane glycoprotein 1 (LAMP1), disrupting lysosome-multivesicular body (MVB) fusion, which protects EVs from degradation. Knockdown of HEXB efficiently inhibits EV release and curbs HCC growth both in vitro and in vivo. Moreover, targeting HEXB by M-31850 significantly inhibits HCC growth, especially when combined with GW4869, an inhibitor of exosome release. Our results underscore the critical role of HEXB as a modulator that promotes EV release during HCC development.

Causal relationship between gut microbiota and puerperal sepsis: a 2-sample Mendelian randomization study.

Background: Some recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis. Methods: This study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p < 1.0 × 10-5. The inverse variance weighted (IVW) parameter was used as the primary method for MR and it was supplemented by other methods. Additionally, a set of sensitivity analytical methods, including the MR-Egger intercept, Mendelian randomized polymorphism residual and outlier, Cochran's Q and the leave-one-out tests were carried out to assess the robustness of our findings. Results: Our study found 3 species of gut microbiota, Lachnospiraceae FCS020, Lachnospiraceae NK4A136, and Ruminococcaceae NK4A214, to be associated with PS. The IVW method indicated an approximately 19% decreased risk of PS per standard deviation increase with Lachnospiraceae FCS020 (OR = 0.81; 95% CI 0.66-1.00, p = 0.047). A similar trend was also found with Lachnospiraceae NK4A136 (OR = 0.80; 95% CI 0.66-0.97, p = 0.024). However, Ruminococcaceae NK4A214 was positively associated with the risk of PS (OR = 1.33, 95% CI: 1.07-1.67, p = 0.011). Conclusion: This two-sample MR study firstly found suggestive evidence of beneficial and detrimental causal associations of gut microbiota on the risk of PS. This may provide valuable insights into the pathogenesis of microbiota-mediated PS and potential strategies for its prevention and treatment.

Double-Cabin Galvanic Cell-Synthesizing Nanoporous, Flower-like, Pb-Containing Pd-Au Nanoparticles for Nonenzymatic Formaldehyde Sensor.

In this work, a novel formaldehyde sensor was constructed based on nanoporous, flower-like, Pb-containing Pd-Au nanoparticles deposited on the cathode in a double-cabin galvanic cell (DCGC) with a Cu plate as the anode, a multiwalled carbon nanotube-modified glassy carbon electrode as the cathode, a 0.1 M HClO4 aqueous solution as the anolyte, and a 3.0 mM PdCl2 + 1.0 mM HAuCl4 + 5.0 mM Pb(ClO4)2 + 0.1 M HClO4 aqueous solution as the catholyte, respectively. Electrochemical studies reveal that the stripping of bulk Cu can induce underpotential deposition (UPD) of Pb during the galvanic replacement reaction (GRR) process, which affects the composition and morphology of Pb-containing Pd-Au nanoparticles. The electrocatalytic activity of Pb-containing nanoparticles toward formaldehyde oxidation was examined in an alkaline solution, and the experimental results showed that formaldehyde mainly caused direct oxidation on the surface of Pb-containing Pd-Au nanoparticles while inhibiting the formation of CO poison to a large degree. The proposed formaldehyde sensor exhibits a linear amperometric response to formaldehyde concentrations from 0.01 mM to 5.0 mM, with a sensitivity of 666 µA mM-1 cm-2, a limit of detection (LOD) of 0.89 µM at triple signal-to-noise, rapid response, high anti-interference ability, and good repeatability.

[Correlation Analysis between STING Promoter Polymorphism and Susceptibility to Infection after Chemotherapy for Multiple Myeloma].

OBJECTIVE: To investigate the correlation between the stimulator of interferon genes (STING ) promoter polymorphism and the susceptibility to infection after chemotherapy for multiple myeloma. METHODS: A total of 102 patients who had undergone chemotherapy for multiple myeloma in our hospital from January 2016 to July 2022 were selected. Depending on the presence or absence of infection after chemotherapy, the enrolled patients were divided into infection group (53 cases) and non-infection group (49 cases). The infection sites and distribution characteristics of pathogenic bacteria of the infection group were analyzed. The genotype distribution of STING gene promoter rs587777609 was compared between the two groups, and the risk factors of infection after chemotherapy for multiple myeloma were analyzed. RESULTS: For infection site, digestive system, respiratory system, urinary system, skin and mucous membranes accounted for 43.40%, 26.42%, 20.75%, and 9.43%, respectively. For pathogenic bacteria, Gram-negative bacteria, Gram-positive bacteria and fungi accounted for 57.14%, 26.98%, and 15.87%, respectively. The CC genotype frequency of STING gene rs587777609 locus in the infection group was lower than that in the non-infection group, while the TT genotype frequency was higher than that in the non-infection group (P < 0.05). The proportions of patients with diabetes, chronic obstructive pulmonary disease, renal insufficiency, serum albumin level< 35 g/L, ISS stage III, mechanical ventilation, and indwelling catheter in the infection group were higher than those in the non-infection group (P < 0.05). Multivariate logistic regression analysis showed that diabetes (OR =1.992), serum albumin level< 35 g/L (OR =2.782), ISS stage III (OR =2.707), mechanical ventilation (OR =3.031), and TT genotype (OR =2.401) were risk factors of infection after chemotherapy for multiple myeloma (P < 0.05). CONCLUSION: There is a correlation between STING promoter polymorphism and the susceptibility to infection after chemotherapy for multiple myeloma, and patients with TT genotype have a higher risk of infection.

Highly Tribo-Positive Nylon-11 Film Fabricated by Multiscale Structural Regulation through a Roll-to-Roll Processing.

Triboelectric polymers have attracted extensive attention due to their great electron-accepting and electron-donating properties in contact electrification as well as their flexible and low-cost merits and have become promising electrode materials in triboelectric nanogenerators (TENGs). However, most research has exclusively focused on improving the electron capture capability of the triboelectric layer, neglecting to enhance the electron-donating capability, which leads to a low output performance of TENG and limits its practical application. In this study, we developed a method to fabricate highly tribo-positive Nylon-11 film through roll-to-roll processing. Paired with the poly(tetrafluoroethylene) triboelectric layer, the transferred charge density of contact-separation TENG based on Nylon-11 film prepared by this method reaches 291.1 µC/m2, which has been improved by 12.4% compared with the conventional compression molding sample. The novel fabricating method can regulate the surface functional groups to achieve higher surface potential and obtain a favorable pseudohexagonal crystal phase, leading to an increasing transferred charge density in triboelectrification. Additionally, it has been analyzed that higher chemical potential of materials can facilitate the transfer of electrons from the triboelectric polymer surface. This study provides a nonadditive, simple, and effective strategy to fabricate excellent tribo-positive material, which can significantly enhance the performance of TENG.

Source, preservation and re-suspension of 239,240Pu in a well dated peat core collected from northwest China.

Owning to the high radiotoxicity in high concentrations, as well as the irreplaceability in quantifying soil erosion rates, demarcating the Anthropocene, and dating of sediment, anthropogenic 239,240Pu have drawn high attention. However, the source in specific areas, preservation characteristics in different environment media, and re-distribution process after the cessation of atmospheric nuclear weapons tests, have not been fully understood, which obscures the exact start year, temporal variation, and deposition flux of 239,240Pu in sedimentary records, and hinders the wide application of 239,240Pu in environment study. A sediment core from the Yiwu peat bog with dominance of atmospheric deposition in the source material, simple sedimentary environment, and high dust deposition flux, was collected to examine the 239,240Pu, and explore the source, preservation, and re-distribution process. The double peaks of 239,240Pu in 1952 CE and 1963 CE, as well as 240Pu/239Pu ratios of 0.163-0.190 with an average of 0.177 ± 0.010 confirmed that the 239,240Pu source originated predominantly from global fallout. The minimal vertical migration of plutonium in the Yiwu peat core was attributed to the near-neutral pH condition. The high inventory of 128 ± 7 Bq m-2, as well as the atypical negative correlation between 239,240Pu concentrations and organic matter content (r = - 0.79, P < 0.01), was attributed to the contribution of 239,240Pu re-suspended with dust from the neighboring Gobi Desert, particularly in the cold and dry years. The total re-suspended 239,240Pu was estimated to be 77 Bq m-2, exceeding the direct fallout level of 51 Bq m-2 during 1945-2016 CE. In this study, the specified deposition pattern of 239,240Pu after the cessation of atmospheric nuclear weapons was established, providing an important standard for multiple environmental studies, and the re-suspended amount of 239,240Pu in a typical arid area was quantified for the first time.

Uncovering the characteristics of the gut microbiota in patients with ischemic stroke and hemorrhagic stroke.

This study aimed to explore the gut microbiota characteristics of ischemic and hemorrhagic stroke patients. A case-control study was conducted, and high-throughput sequencing of the V4-V5 region of 16S rRNA was used to analyze the differences in gut microbiota. The results showed that Proteobacteria was significantly increased in the ischemic stroke group compared with the healthy control group, while Fusobacteria was significantly increased in the hemorrhagic stroke group. In the ischemic stroke group, Butyricimonas, Alloprevotella, and Escherichia were significantly more abundant than in the healthy control group. In the hemorrhagic stroke group, Atopobium, Hungatella, Eisenbergiella, Butyricimonas, Odonbacter, Lachnociostridium, Alistipes, Parabacteroides, and Fusobacterium were significantly more abundant than in the healthy control group. Additionally, Alloprevotella, Ruminococcus, and Prevotella were significantly more abundant in the ischemic stroke group than in the hemorrhagic stroke group. The gut microbiota of ischemic and hemorrhagic stroke patients has significant diversity characteristics. These results provide new theoretical basis for exploring the prevention and treatment of different types of stroke through gut microbiota research.

Simple and Efficient Synthesis of Ruthenium(III) PEDOT:PSS Complexes for High-Performance Stretchable and Transparent Supercapacitors.

In the evolving landscape of portable electronics, there is a critical demand for components that meld stretchability with optical transparency, especially in supercapacitors. Traditional materials fall short in harmonizing conductivity, stretchability, transparency, and capacity. Although poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) stands out as an exemplary candidate, further performance enhancements are necessary to meet the demands of practical applications. This study presents an innovative and effective method for enhancing electrochemical properties by homogeneously incorporating Ru(III) into PEDOT:PSS. These Ru(III) PEDOT:PSS complexes are readily synthesized by dipping PEDOT:PSS films in RuCl3 solution for no longer than one minute, leveraging the high specific capacitance of Ru(III) while minimizing interference with transmittance. The supercapacitor made with this Ru(III) PEDOT:PSS complex demonstrated an areal capacitance of 1.62 mF cm-2 at a transmittance of 73.5%, which was 155% higher than that of the supercapacitor made with PEDOT:PSS under comparable transparency. Notably, the supercapacitor retained 87.8% of its initial capacitance even under 20% tensile strain across 20,000 cycles. This work presents a blueprint for developing stretchable and transparent supercapacitors, marking a significant stride toward next-generation wearable electronics.

Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial.

Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 103/µL at baseline and 300 mg/day otherwise. OS was a secondary endpoint. Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].

Immunization with a peptide mimicking lipoteichoic acid induces memory B cells in BALB/c mice.

BACKGROUND: There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. METHODS: BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student's t-test. RESULTS: The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. CONCLUSIONS: Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.

Quantitative estimation of dust transport in the desert region of northwest China by plutonium isotopes.

Dust is an important source of atmospheric pollution, and quantitative estimation of desert dust transport is crucial for air pollution control. In this study, five typical sandy soil profiles in the Tengger Desert were collected and analyzed for 239,240Pu concentration and 240Pu/239Pu atomic ratios in order to identify the source of 239,240Pu in this area and explore the sedimentary characteristics of dust in different profiles. The results revealed that the concentrations of 239,240Pu in the soil profiles were between 0.002 and 0.443 mBq/g with an exception of the deep layer soil at one site. The measured atomic ratios of 240Pu/239Pu are at the global atmospheric fallout level with a mean of 0.184 ± 0.020, indicating that global fallout is the dominant source of plutonium in this region. The total inventories of 239,240Pu in the reference sites in this area were estimated to be 39.2-44.6 Bq/m2, this is in agreement with the value from the global fallout of atmospheric nuclear weapon tests at the similar latitude (30-40 °N: 42 Bq/m2). The estimated erosion rate in the erosion profile utilizing soil erosion intensity mode is 2491 t/km2/yr and the soil erosion depth is 9.86 cm, While, the stacking rate of the accumulation profile is 1383 t/km2/yr, and the depth of accumulation is estimated to be 5.48 cm. The difference between the erosion and accumulation profiles indicated that approximately 1107 t/km2/yr of dust was exported from the Gobi landform area of the Tengger Desert, which might be transported long distance in the downwind direction.

Global research trends and prospects of cellular metabolism in colorectal cancer.

BACKGROUND: An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer (CRC). However, no work is currently available to synthesize the field through bibliometrics. AIM: To analyze the development in the field of "glucose metabolism" (GM), "amino acid metabolism" (AM), "lipid metabolism" (LM), and "nucleotide metabolism" (NM) in CRC by visualization. METHODS: Articles within the abovementioned areas of GM, AM, LM and NM in CRC, which were published from January 1, 1991, to December 31, 2022, are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19. RESULTS: The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields. Meanwhile, China and the United States were two of the most prominent contributors in these four areas. In addition, Gang Wang, Wei Jia, Maria Notarnicola, and Cornelia Ulrich ranked first in publication numbers, while Jing-Yuan Fang, Senji Hirasawa, Wei Jia, and Charles Fuchs were the most cited authors on average in these four fields, respectively. "Gut microbiota" and "epithelial-mesenchymal transition" emerged as the newest burst words in GM, "gut microbiota" was the latest outburst word in AM, "metastasis", "tumor microenvironment", "fatty acid metabolism", and "metabolic reprogramming" were the up-to-date outbreaking words in LM, while "epithelial-mesenchymal transition" and "apoptosis" were the most recently occurring words in NM. CONCLUSION: Research in "cellular metabolism in CRC" is all the rage at the moment, and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC. Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.