Granzyme B PET/CT Imaging Evaluates Early Response to Immunotherapy in Gastric Cancer.

In several malignancies, only a limited number of patients respond to immune checkpoint inhibitors. Predicting and monitoring responses to these inhibitors represent an unmet clinical need. Here, we developed a PET/CT probe targeting granzyme B, [68Ga]Ga-NOTA-Gly-Gly-Gly-Ile-Glu-Pro-Asp-CHO (GSI), and aimed to investigate whether it can be used to monitor the effects of immune checkpoint inhibitors early in the course of therapy. Methods: Seventy-two patients with gastric cancer (stages III-IV) were recruited for [68Ga]Ga-DOTA-GSI PET/CT imaging after 2 or 3 cycles of the immunotherapy, and 40 patients were included in the final analysis. The SUVmax of primary tumors (SUVmax-t), SUVmax of metastatic lymph nodes (SUVmax-LN), and SUVmax of normal tissues (liver and blood pool) were measured, and their target-to-liver background ratio (TLR) and target-to-blood background ratio (TBR) were denoted for primary tumors as TLRtumor and TBRtumor and for metastatic lymph nodes as TLRLN and TBRLN, respectively. The treatment responses were assessed within 1 wk after full-course treatment according to RECIST version 1.1. Wilcoxon rank-sum tests were used to compare the PET/CT parameters between responders and nonresponders. Receiver operating characteristic curve analysis was used to assess the diagnostic efficacy of [68Ga]Ga-DOTA-GSI PET/CT parameters in identifying responders. Two-tailed P value of less than 0.05 was considered statistically significant. Results: We found that SUVmax-t, TLRtumor, TBRtumor, SUVmax-LN, and TBRLN were higher in responders than in nonresponders (2.49 ± 0.58 vs. 1.55 ± 0.48, P = 0.000; 2.24 ± 0.48 vs. 1.74 ± 0.67, P = 0.007; 1.38 ± 0.43 vs. 0.90 ± 0.23, P = 0.000; 2.24 ± 0.99 vs. 1.42 ± 0.55, P = 0.003; and 1.28 ± 0.68 vs. 0.83 ± 0.32, P = 0.012, respectively). According to receiver operating characteristic curve analysis, the area under the curve for SUVmax-t, TBRtumor, TLRtumor, SUVmax-LN, TLRLN, and TBRLN was 0.886, 0.866, 0.746, 0.772, 0.648, and 0.731, respectively. The threshold of SUVmax-t was 2.05, and its sensitivity and specificity were 81.0% and 84.2%, respectively. In addition, multivariate logistic regression indicated that TBRtumor was an independent predictor of treatment response (P = 0.03). Conclusion: Our results indicated that [68Ga]Ga-DOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.

Upregulated DNMT3a coupling with inhibiting p62-dependent autophagy contributes to NNK tumorigenicity in human bronchial epithelial cells.

NNK, formally known as 4-(methyl nitrosamine)-1-(3-pyridyl)-1-butanoe, is a potent chemical carcinogen prevalent in cigarette smoke and is a key contributor to the development of human lung adenocarcinomas. On the other hand, autophagy plays a complex role in cancer development, acting as a "double-edged sword" whose impact varies depending on the cancer type and stage. Despite this, the relationship between autophagy and NNK-induced lung carcinogenesis remains largely unexplored. Our current study uncovers a marked reduction in p62 protein expression in both lung adenocarcinomas and lung tissues of mice exposed to cigarette smoke. Interestingly, this reduction appears to be contingent upon the activity of extrahepatic cytochrome P450 (CYP450), revealing that NNK metabolic activation by CYP450 enzyme escalates its potential to induce p62 downregulation. Further mechanistic investigations reveal that NNK suppresses autophagy by accelerating the degradation of p62 mRNA, thereby promoting the malignant transformation of human bronchial epithelial cells. This degradation process is facilitated by the hypermethylation of the Human antigen R (HuR) promoter, resulting in the transcriptional repression of HuR - a key regulator responsible for stabilizing p62 mRNA through direct binding. This hypermethylation is triggered by the activation of ribosomal protein S6, which is influenced by NNK exposure and subsequently amplifies the translation of DNA methyltransferase 3 alpha (DNMT3a). These findings provide crucial insights into the nature of p62 in both the development and potential treatment of tobacco-related lung cancer.

Maternal adiposity and perinatal and offspring outcomes: an umbrella review.

Maternal adiposity deleteriously affects obstetrical health and has been associated with long-term adverse consequences in offspring. Here we conducted an umbrella review encompassing 194 observational meta-analyses, 10 Mendelian randomization studies and 748 interventional meta-analyses to appraise the published evidence on the associations between maternal adiposity and perinatal and offspring outcomes. Evidence grading suggested that 17 (8.8%) observational meta-analyses were supported by convincing evidence for 12 outcomes: maternal adiposity was associated with an increased risk of caesarean delivery following labour induction, infant mortality, Apgar score <7 at 1 min, antenatal depression, offspring overweight and obesity, early timing of puberty onset in daughters, attention deficit hyperactivity disorder, cerebral palsy, congenital heart disease and spina bifida (OR/RR ranging from 1.14 to 2.31), as well as increased offspring body fat percent and fat mass (SMD 0.31 and 0.35, respectively). Among these outcomes, interventional meta-analyses supported that maternal weight loss interventions significantly reduced the risk of antenatal depression but not low Apgar scores; these interventions also could not reduce offspring fat mass or body fat percent. Evidence from Mendelian randomization studies supported a causal relationship between maternal adiposity and gestational diabetes mellitus, preeclampsia, birth size and offspring adiposity. Our findings highlight that while observational meta-analyses reveal associations between maternal adiposity and various adverse perinatal and offspring outcomes, convincing, unbiased evidence or support from Mendelian randomization studies is limited. Maternal pre-conceptional and prenatal weight loss interventions can reduce some, but not all, of these adverse effects.

Induction of cytochrome P450 via upregulation of CAR and PXR: a potential mechanism for altered florfenicol metabolism by macranthoidin B in vivo.

Introduction: Macranthoidin B (MB) is a primary active component of Flos Lonicerae. In Chinese veterinary clinics, Flos Lonicerae is frequently used in combination with florfenicol to prevent and treat infections in livestock and poultry. However, potential interactions between Flos Lonicerae and florfenicol remain unclear. To systematically study these interactions, it is crucial to investigate the individual phytochemicals within Flos Lonicerae. Therefore, MB was selected for this study to assess its effect on the pharmacokinetics of florfenicol in vivo and to explore the underlying mechanisms involved. Methods: Male Sprague-Dawley rats were administered MB (60 mg/kg BW) or sterile water orally for 7 consecutive days. On the 8th day, a single oral dose of florfenicol (25 mg/kg BW) was given. Florfenicol pharmacokinetics were analyzed using ultra-high performance liquid chromatography. The hepatic expression levels of cytochrome P450 (CYP1A2, CYP2C11, CYP3A1), UDP-glucuronosyltransferase (UGT1A1), P-glycoprotein (P-gp), and nuclear receptors, including constitutive androstane receptor (CAR), pregnane X receptor (PXR), and retinoid X receptor alpha (RXRα), were quantified via reverse transcription-quantitative polymerase chain reaction and Western blotting (WB). Hepatic CYP1A2 and CYP2C11 activities were measured using a cocktail method. Additionally, the subcellular expression and localization of CAR, PXR, and RXRαin hepatocytes was assessed using WB and immunofluorescence staining. Results: MB significantly reduces the AUC(0-∞) and MRT(0-∞) of florfenicol. MB also markedly upregulates the mRNA and protein expression of hepatic CYP1A2 and CYP2C11, along with their catalytic activities. Substantial upregulation of CAR and PXR proteins occurs in the hepatocyte nucleus, along with significant nuclear colocalization of the transcriptionally active CAR/RXRα and PXR/RXRαheterodimers, indicating MB-induced nuclear translocation of both CAR and PXR. Discussion: These findings suggest that MB-induced alterations in florfenicol pharmacokinetics, particularly its accelerated elimination, may be due to increased expression and activities of CYP1A2 and CYP2C11, with CAR and PXR potentially involved in these regulatory effects. Further investigation is yet needed to fully elucidate the clinical implications of these interactions concerning the efficacy of florfenicol in veterinary medicine.

Pelvic floor dysfunction in postpartum women: A cross-sectional study.

BACKGROUND: Pelvic floor dysfunction (PFD) is a disease of weakened pelvic floor support tissues, leading to changes in the pelvic organ position and function of pelvic organs, with long-term effects on women. This study aimed to assess pelvic floor function using electrophysiology and clinical symptoms, exploring the risk factors for PFD one month postpartum. METHODS: This cross-sectional study included 845 women from postpartum outpatient clinic of Nantong Affiliated Hospital from August 2019 to October 2021. Pelvic floor muscle strength was evaluated via pelvic floor surface electromyography. Clinical symptoms (urinary incontinence (UI) and pelvic organ prolapse) were diagnosed by gynecologists. Sociodemographic, pregnancy, and obstetrical data were obtained from self-reported questionnaires and electronic records. RESULTS: The study identified maternal age, parity, immigrant status, and economic income as factors were related to PFD. Gestational constipation increased the risk of abnormal resting muscle strength (OR:1.553, 95%CI: 1.022-2.359). Cesarean delivery was associated with higher rates of abnormal resting muscle strength than vaginal delivery (post-resting stage: OR, 2.712; 95% CI, 1.189-6.185), but a decreased incidence of UI (OR: 0.302; 95% CI, 0.117-0.782). Increased gestational weight gain was correlated with a greater risk of developing UI (OR:1.030, 95%CI: 1.002-1.058). Women with vaginal inflammation faced a higher risk of abnormal fast-twitch muscle (OR: 2.311, 95%CI: 1.125-4.748). CONCLUSIONS: In addition to uncontrollable factors like mode of delivery, age, and parity, interventions targeting weight gain and constipation during pregnancy and vaginal flora could mitigate the risks of PFD. Educational programs for pregnant women should emphasize a proper diet and lifestyle. For women with vaginal inflammation, clinical treatment should be carried out as soon as possible to avoid further aggravating the damage to the pelvic floor muscles.

Amyloid Proteins Adhesive for Slippery Liquid-Infused Porous Surfaces.

Biomimetic slippery liquid-infused porous surfaces (SLIPS) have emerged as a promising solution to solve the limitations of superhydrophobic surfaces, such as inadequate durability in corrosion protection and a propensity for frosting. However, the challenge of ensuring strong, lasting adhesion on diverse materials to enhance the durability of the lubricant layer remains. The research addresses this by leveraging amyloid phase-transitioned lysozyme (PTL) as an adhesive interlayer, conferring stable attachment of SLIPS across a variety of substrates, including metals, inorganics, and polymers. The silica-textured interface robustly secures the lubricant with a notably low sliding angle of 1.15°. PTL-mediated adhesion fortifies the silicone oil attachment to the substrate, ensuring the retention of its repellent efficacy amidst mechanical stressors like ultrasonication, water scrubbing, and centrifugation. The integration of robust adhesion, cross-substrate compatibility, and durability under stress affords the PTL-modified SLIPS exceptional anti-fouling, anti-icing, and anti-corrosion properties, marking it as a leading solution for advanced protective applications.

Ru incorporated into Se vacancy-containing CoSe2 as an efficient electrocatalyst for alkaline hydrogen evolution.

In alkaline media, slow water dissociation leads to poor overall hydrogen evolution performance. However, Ru catalysts have a certain water dissociation performance, thus regulating the Ru-H bond through vacancy engineering and accelerating water dissociation. Herein, an excellent Ru-based electrocatalyst for the alkaline HER has been developed by incorporating Ru into Se vacancy-containing CoSe2 (Ru-VSe-CoSe2). The results from X-ray photoelectron spectroscopy, kinetic isotope effect, and cyanide poisoning experiments for four catalysts (namely Ru-VSe-CoSe2, Ru-CoSe2, VSe-CoSe2, and CoSe2) reveal that Ru is the main active site in Ru-VSe-CoSe2 and the presence of Se vacancies greatly facilitates electron transfer from Co to Ru via a bridging Se atom. Thus, electron-rich Ru is formed to optimize the adsorption strength between the active site and H*, and ultimately facilitates the whole alkaline HER process. Consequently, Ru-VSe-CoSe2 exhibits an excellent HER activity with an ultrahigh mass activity of 44.2 A mgRu-1 (20% PtC exhibits only 3 A mgRu-1) and a much lower overpotential (29 mV at 10 mA cm-2) compared to Ru-CoSe2 (75 mV), VSe-CoSe2 (167 mV), CoSe2 (190 mV), and commercial Pt/C (41 mV). In addition, the practical application of Ru-VSe-CoSe2 is illustrated by designing a Zn-H2O alkaline battery with Ru-VSe-CoSe2 as the cathode catalyst, and this battery shows its potential application with a maximum power density of 4.9 mW cm-2 and can work continuously for over 10 h at 10 mA cm-2 without an obvious decay in voltage.

Polyunsaturated triacylglycerol accumulation mainly attributes to turnover of de novo-synthesized membrane lipids in stress-induced starchless Chlamydomonas.

KEY MESSAGE: Assembly of PUFA-attached TAGs is intimately correlated to turnover of newly formed membrane lipids in starch-deficient Chlamydomonas exposed to high light and nitrogen stress under air-aerated mixotrophic conditions. Triacylglycerols (TAGs) rich in polyunsaturated fatty acids (PUFAs) in microalgae have attracted extensive attention due to its promising application in nutraceuticals and other high-value compounds. Previous studies revealed that PUFAs accumulated in TAG primarily derived from the dominant membrane lipids, monogalactosyldiacylglycerolipid, digalactosyldiacylglycerol and diacylglycerol-N,N,N-trimethylhomoserine (DGTS), in the model alga Chlamydomonas reinhardtii. However, their respective contribution to PUFA-attached TAG integration has not been clearly deciphered, particularly in starchless Chlamydomonas that hyper-accumulates TAG. In this study, the starchless C. reinhardtii BAFJ5 was mixotrophically cultivated in photobioreactors aerated with air (0.04% CO2), and we monitored the dynamic changes in growth, cellular carbon and nitrogen content, photosynthetic activity, biochemical compositions, and glycerolipid remodeling under high light and nitrogen starvation conditions. The results indicated that multiple PUFAs continually accumulated in total lipids and TAG, and the primary distributors of these PUFAs gradually shifted from membrane lipids to TAG in stress-induced BAFJ5. The stoichiometry analyses showed that the PUFA-attached TAG assembly attributed to turnover of not only the major glycerolipids, but also the phospholipids, phosphatidylethanolamine (PE) and phosphatidylglycerol. Specifically, the augmented C16:3n3 and C18:3n3 in TAG mainly originated from de novo-synthesized galactolipids, while the cumulative C18:3n6 and C18:4n3 in TAG were intimately correlated with conversion of the newly formed DGTS and PE. These findings emphasized significance of PUFA-attached TAG formation dependent on turnover of de novo assembled membrane lipids in starch-deficient Chlamydomonas, beneficial for enhanced production of value-added lipids in microalgae.

A sex-oriented analysis concerning skeletal muscle quantity and quality and associations to quality of life in hospitalized patients with cirrhosis.

BACKGROUND: There is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities. METHODS: Totally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity. RESULTS: The study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P < 0.001) and SMI (48.8 versus 42.2 cm2/m2, P < 0.001) were significantly higher in males relative to females, with comparable myosteatosis prevalence (15.3 versus 16.7%, P = 0.708). Self-care, usual activities and pain within EQ-5D scale were more prevalent in the sarcopenia compared with non-sarcopenia groups across entire population and stratified by sex. The SMI values exhibited a significantly linear correlation with EQ-5D utility index in male but not female patients (P for non-linearity = 0.281). In multiple analysis, SMI or the presence of sarcopenia was both significantly associated with EQ-5D utility index. Subgroup analyses unveiled no discernible interactions between sarcopenia and EQ-5D utility index. CONCLUSIONS: Muscle quantity measured by SMI was associated with declined HRQoL in males rather than females, whereas no associations were found regarding muscle quality measured by IMAC in both sexes. It is tempting to manage sarcopenia by increasing SMI levels as high as possible in hopes of achieving better health consequence. Our findings represent the importance of connecting CT-demarcated body composition abnormalities to meaningful patient-centered outcomes. Future targeted studies with sizable multi-center populations are warranted to clarify this causality, and in consequence develop optimized intervention against sarcopenia/myosteatosis or key determinants concerning impaired HRQoL.

BRD9 promotes the progression of gallbladder cancer via CST1 upregulation and interaction with FOXP1 through the PI3K/AKT pathway and represents a therapeutic target.

Gallbladder cancer (GBC) is highly aggressive and has poor prognosis, with most patients only diagnosed at an advanced stage. Furthermore, treatment options are limited, and their effect is unsatisfactory. Bromodomain-containing protein (BRD) is an epigenetic regulator that plays a carcinogenic role in several tumors, including squamous cell lung cancer, acute myeloid leukemia, synovial sarcoma, and malignant rhabdomyosarcoma. However, the expression, biological function, and molecular mechanisms of action of BRD9 in GBC are still unknown. Kaplan-Meier analysis, qRT-PCR, and analysis of clinical features were used to assess the clinical significance of BRD9 in GBC. Cell Counting Kit-8 and colony formation assays were performed to determine the effects of BRD9 on cell growth. The functional role of BRD9 in GBC was explored using qRT-PCR, western blotting, siRNA, and CHIP-qPCR. mRNA sequencing was performed to explore the underlying mechanisms of BRD9, and a nude mouse model of GBC was established to explore the anti-tumor effects of the BRD9 inhibitor I-BRD9 in vivo. BRD9 expression was elevated in GBC tissues compared with adjacent non-tumor tissues, and high BRD9 expression was associated with poor prognosis in patients with GBC. BRD9 knockdown by siRNA significantly decreased cell growth. Targeting BRD9 with I-BRD9 inhibited the proliferation of GBC cells without significant toxic effects. Additionally, I-BRD9 treatment suppressed CST1 expression in GBC cell lines, thereby inhibiting the PI3K-AKT pathway. The transcription factor FOXP1 was found to interact with BRD9 to regulate CST1 expression. Collectively, these results suggest that BRD9 may be a promising biomarker and therapeutic target for GBC.

Utilization of microdroplets as optical lenses for surface-enhanced Raman spectroscopy (SERS) enhancement on localized silver nanoparticle-decorated porous silicon substrates.

Surface-enhanced Raman spectroscopy (SERS) is a widely used analytical technique known for its high sensitivity and broad applicability. Despite its potential, SERS faces challenges related to detection sensitivity and reproducibility. This study proposes an innovative method to enhance SERS performance by employing water microdroplets as optical lenses on localized silver nanoparticle-decorated porous silicon (LocAg-PS) substrates. The hydrophobic nature of the LocAg-PS substrate not only ensures precise positioning of the microdroplet lenses on the silver nanoparticle grafted pad (AgNP pad) but also forms a plano-convex-like microdroplet lens for the focusing of the excitation laser and the collection of scattered light. Experimental results demonstrate that using microdroplet lenses enhances the SERS signal intensity and reproducibility, providing a rapid and cost-effective solution for advanced SERS analysis.

Encapsulated lactiplantibacillus plantarum improves Alzheimer's symptoms in APP/PS1 mice.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder that can result in neurotoxicity and an imbalance in gut microbiota. Probiotics have been shown to play an important role in regulating the gut microbiota, but their viability and bioactivity are often compromised as they traverse the gastrointestinal tract, thereby reducing their efficacy and limiting their clinical utility. RESULTS: In this work, layer-by-layer (LbL) encapsulation technology was used to encapsulate Lactiplantibacillus plantarum (LP) to improve the above shortcomings. Studies in APPswe/PS1dE9 (APP/PS1) transgenic mice show that LbL-encapsulated LP ((CS/SP)2-LP) protects LP from gastrointestinal damage while (CS/SP)2-LP treatment It improves brain neuroinflammation and neuronal damage in AD mice, reduces Aß deposition, improves tau protein phosphorylation levels, and restores intestinal barrier damage in AD mice. In addition, post-synaptic density protein 95 (PSD-95) expression increased in AD mice after treatment, indicating enhanced synaptic plasticity. Fecal metabolomic and microbiological analyzes showed that the disordered intestinal microbiota composition of AD mice was restored and short-chain fatty acids (SCFAs) levels were significantly increased after (CS/SP)2-LP treatment. CONCLUSION: Overall, the above evidence suggests that (CS/SP)2-LP can improve AD symptoms by restoring the balance of intestinal microbiota, and (CS/SP)2-LP treatment will provide a new method to improve the symptoms of AD patients.

Upcycling of nutrients from kitchen waste: Integration of anaerobic digestion system and microbial protein production system.

To upcycle the nutrients from kitchen waste (KW), an integrated system consisting of anaerobic digestion (AD) reactor and microbial protein (MP) production reactor was established in this study. The subsystem I (AD system) demonstrated an efficient bio-energy production (282.37 mL CH4/g VS), with 553.54 mg/L of NH4+-N remained in the digestate. The subsystem II (MP production system) utilized the nitrogenous constituents of the digestate, with 2.04 g/L MP production. In order to further enhance the recovery efficiency, C/N ratio in the subsystem II was studied. NH4+-N recovery efficiency was 23.08% higher after C/N ratio optimization along with 0.24 g/L increment on MP production. Over 0.7 g/L of essential amino acids was obtained, according with the qualitative necessary for the feeds. Also, the key enzyme abundance of CO2 releasing and amino acid biosynthesis was obviously increased with max. 55.21%. Meanwhile, the integrated system was profitable via a simplified economic assessment.

Overexpression of two DELLA subfamily genes MiSLR1 and MiSLR2 from mango promotes early flowering and enhances abiotic stress tolerance in Arabidopsis.

Gibberellic acids (GAs) are a group of endogenous phytohormones that play important roles in plant growth and development. SLENDER RICE (SLR) serves as a vital component of the DELLA gene family, which plays an irreplaceable role in regulating plant flowering and height, as well as stress responses. SLR gene has not been reported in mango, and its function is unknown. In present study, two DELLA subfamily genes MiSLR1 and MiSLR2 were identified from mango. MiSLR1 and MiSLR2 were highly expressed in the stems of the juvenile stage, but were expressed at a low level in flower buds and flowers. Gibberellin treatment could up-regulate the expression of MiSLR1 and MiSLR2 genes, but gibberellin biosynthesis inhibitor prohexadione-calcium (Pro-Ca) and paclobutrazol (PAC) treatments significantly down-regulated the expression of MiSLR1, while MiSLR2 was up-regulated. The expression levels of MiSLR1 and MiSLR2 were up-regulated under both salt and drought treatments. Overexpression of MiSLR1 and MiSLR2 genes significantly resulted early flowering in transgenic Arabidopsis and significantly up-regulated the expression levels of endogenous flower-related genes, such as SUPPRESSOR OF CONSTANS1 (SOC1), APETALA1 (AP1), and FRUITFULL (FUL). Interestingly, MiSLR1 significantly reduced the height of transgenic plants, while MiSLR2 gene increased. Overexpression of MiSLR1 and MiSLR2 increased seed germination rate, root length and survival rate of transgenic plants under salt and drought stress. Physiological and biochemical detection showed that the contents of proline (Pro) and superoxide dismutase (SOD) were significantly increased, while the contents of malondialdehyde (MDA) and H2O2 were significantly decreased. Additionally, protein interaction analysis revealed that MiSLR1 and MiSLR2 interacted with several flowering-related and GA-related proteins. The interaction between MiSLR with MiGF14 and MiSOC1 proteins was found for the first time. Taken together, the data showed that MiSLR1 and MiSLR2 in transgenic Arabidopsis both regulated the flowering time and plant height, while also acting as positive regulators of abiotic stress responses.

PTBP3 Mediates IL-18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer.

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA-seq analysis, it is found high expression of the splicing factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping of interleukin-18 (IL-18), resulting in the expression of ΔIL-18, an isoform specifically expressed in tumors. That ΔIL-18 promotes GBC immune escape by down-regulating FBXO38 transcription levels in CD8+T cells to reduce PD-1 ubiquitin-mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL-18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL-18 production displayed anti-tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL-18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL-18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL-18 pre-mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.

Enhanced catalytic performance through a single-atom preparation approach: a review on ruthenium-based catalysts.

The outstanding catalytic properties of single-atom catalysts (SACs) stem from the maximum atom utilization and unique quantum size effects, leading to ever-increasing research interest in SACs in recent years. Ru-based SACs, which have shown excellent catalytic activity and selectivity, have been brought to the frontier of the research field due to their lower cost compared with other noble catalysts. The synthetic approaches for preparing Ru SACs are rather diverse in the open literature, covering a wide range of applications. In this review paper, we attempt to disclose the synthetic approaches for Ru-based SACs developed in the most recent years, such as defect engineering, coordination design, ion exchange, the dipping method, and electrochemical deposition etc., and discuss their representative applications in both electrochemical and organic reaction fields, with typical application examples given of: Li-CO2 batteries, N2 reduction, water splitting and oxidation of benzyl alcohols. The mechanisms behind their enhanced catalytic performance are discussed and their structure-property relationships are revealed in this review. Finally, future prospects and remaining unsolved issues with Ru SACs are also discussed so that a roadmap for the further development of Ru SACs is established.

Oxygen vacancy-regulated nanorod array electrodes for boosting the electrocatalytic synthesis of ammonia from nitrate wastewater.

The adsorption of nitrate is the key to enhancing the electrocatalytic nitrate reduction reaction (NitRR). Herein, a typical hydrolysis-coupled redox (HCR) reaction has been designed to prepare unique 3D Cu/Fe2O3 core-shell nanorod array cathodes with controllable oxygen vacancy concentrations for NitRR. The optimal Cu/Fe2O3-13 achieves a high nitrate conversion of 99.10% and ammonia selectivity of 98.30%. The outstanding electrochemical performance is attributed to the enhancement mechanism of OVs and a unique nanorod array structure with a high density of surface-exposed OVs and high-throughput transport pathways for ion-aspects.

A bibliometric analysis of contrast-enhanced ultrasound over the past twenty years.

Background: Contrast-enhanced ultrasound (CEUS) technology has been developed for decades, and its application is becoming increasingly more extensive. In this study, bibliometrics was used to characterize the development status of CEUS over the past 20 years and to identify future research hotspots. Methods: We collected data from the Web of Science and analyzed the literature related to CEUS published from 2002 to 2022. We examined 6,382 publications and analyzed the publication year, country of origin, affiliated institutions, authors, journal, categories, keywords, and research frontiers within the relevant literature. Using bibliometric analysis, we aimed to determine the general research direction and current publication trends. This allowed us to identify the most prolific and outstanding authors, institutions, countries, and keywords in CEUS research. For data collection, analysis, and visualization, we employed VOSviewer (Leiden University, Leiden, the Netherlands), Excel (Microsoft Corp., Redmond, WA, USA), CiteSpace, and biblioshiny. These tools helped us gather, analyze, and visualize the data effectively. Results: The analyzed publications indicated a consistent upward trend in the number of works published between 2002 and 2022. Notably, China and Sun Yat-sen University emerged as the most prolific countries and institutions, respectively. China published 391 articles with 5,817 citations and was the leader in terms of international cooperation. Moreover, pediatrics-related keywords have surged in frequency in recent years. Conclusions: The amount of research on CEUS has increased rapidly and continues to grow, with China being at the forefront of this research field. The application of CEUS in some pediatric diseases is a recent research hotspot and perhaps warrants close attention.

Prognostic Impact of Neoadjuvant Chemotherapy in Localized or Locoregionally Advanced Gallbladder Cancer: A Population-Based and Propensity Score Matched SEER Analysis.

BACKGROUND: The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis. METHODS: Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT. RESULTS: Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups. CONCLUSIONS: NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.

A Self-Powered, Skin Adhesive, and Flexible Human-Machine Interface Based on Triboelectric Nanogenerator.

Human-machine interactions (HMIs) have penetrated into various academic and industrial fields, such as robotics, virtual reality, and wearable electronics. However, the practical application of most human-machine interfaces faces notable obstacles due to their complex structure and materials, high power consumption, limited effective skin adhesion, and high cost. Herein, we report a self-powered, skin adhesive, and flexible human-machine interface based on a triboelectric nanogenerator (SSFHMI). Characterized by its simple structure and low cost, the SSFHMI can easily convert touch stimuli into a stable electrical signal at the trigger pressure from a finger touch, without requiring an external power supply. A skeleton spacer has been specially designed in order to increase the stability and homogeneity of the output signals of each TENG unit and prevent crosstalk between them. Moreover, we constructed a hydrogel adhesive interface with skin-adhesive properties to adapt to easy wear on complex human body surfaces. By integrating the SSFHMI with a microcontroller, a programmable touch operation platform has been constructed that is capable of multiple interactions. These include medical calling, music media playback, security unlocking, and electronic piano playing. This self-powered, cost-effective SSFHMI holds potential relevance for the next generation of highly integrated and sustainable portable smart electronic products and applications.