Endoscopic ultrasound-guided biliary drainage vs percutaneous transhepatic bile duct drainage in the management of malignant obstructive jaundice.

BACKGROUND: Malignant obstructive jaundice (MOJ) is a condition characterized by varying degrees of bile duct stenosis and obstruction, accompanied by the progressive development of malignant tumors, leading to high morbidity and mortality rates. Currently, the two most commonly employed methods for its management are percutaneous transhepatic bile duct drainage (PTBD) and endoscopic ultrasound-guided biliary drainage (EUS-BD). While both methods have demonstrated favorable outcomes, additional research needs to be performed to determine their relative efficacy. AIM: To compare the therapeutic effectiveness of EUS-BD and PTBD in treating MOJ. METHODS: This retrospective analysis, conducted between September 2015 and April 2023 at The Third Affiliated Hospital of Soochow University (The First People's Hospital of Changzhou), involved 68 patients with MOJ. The patients were divided into two groups on the basis of surgical procedure received: EUS-BD subgroup (n = 33) and PTBD subgroup (n = 35). Variables such as general data, preoperative and postoperative indices, blood routine, liver function indices, myocardial function indices, operative success rate, clinical effectiveness, and complication rate were analyzed and compared between the subgroups. RESULTS: In the EUS-BD subgroup, hospital stay duration, bile drainage volume, effective catheter time, and clinical effectiveness rate were superior to those in the PTBD subgroup, although the differences were not statistically significant (P > 0.05). The puncture time for the EUS-BD subgroup was shorter than that for the PTBD subgroup (P < 0.05). Postoperative blood routine, liver function index, and myocardial function index in the EUS-BD subgroup were significantly lower than those in the PTBD subgroup (P < 0.05). Additionally, the complication rate in the EUS-BD subgroup was lower than in the PTBD subgroup (P < 0.05). CONCLUSION: EUS-BD may reduce the number of punctures, improve liver and myocardial functions, alleviate traumatic stress, and decrease complication rates in MOJ treatment.

Application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy diagnosis of gastric cancer: Meta-analysis.

BACKGROUND: Gastric cancer is a common malignant tumor of the digestive system worldwide, and its early diagnosis is crucial to improve the survival rate of patients. Indocyanine green fluorescence imaging (ICG-FI), as a new imaging technology, has shown potential application prospects in oncology surgery. The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice. AIM: To assess the diagnostic efficacy of optical imaging in conjunction with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy for gastric cancer. METHODS: Electronic databases such as PubMed, Embase, Medline, Web of Science, and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy. Stata 12.0 software was used for analysis by combining the "bivariable mixed effect model" with the "midas" command. The true positive value, false positive value, false negative value, true negative value, and other information from the included literature were extracted. A literature quality assessment map was drawn to describe the overall quality of the included literature. A forest plot was used for heterogeneity analysis, and P < 0.01 was considered to indicate statistical significance. A funnel plot was used to assess publication bias, and P < 0.1 was considered to indicate statistical significance. The summary receiver operating characteristic (SROC) curve was used to calculate the area under the curve (AUC) to determine the diagnostic accuracy. If there was interstudy heterogeneity (I 2 > 50%), meta-regression analysis and subgroup analysis were performed. RESULTS: Optical imaging involves two methods: Near-infrared (NIR) imaging and fluorescence imaging. A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis. The positive likelihood ratio was 30.39 (95%CI: 0.92-1.00), the sensitivity was 0.95 (95%CI: 0.82-0.99), and the specificity was 1.00 (95%CI: 0.92-1.00). The negative likelihood ratio was 0.05 (95%CI: 0.01-0.20), the diagnostic odds ratio was 225.54 (95%CI: 88.81-572.77), and the SROC AUC was 1.00 (95%CI: The crucial values were sensitivity = 0.95 (95%CI: 0.82-0.99) and specificity = 1.00 (95%CI: 0.92-1.00). The Deeks method revealed that the "diagnostic odds ratio" funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical (P = 0.01), suggesting significant publication bias. Further meta-subgroup analysis revealed that, compared with fluorescence imaging, NIR imaging had greater sensitivity (0.98 vs 0.73). Compared with optical imaging immediately after ICG injection, optical imaging after 20 minutes obtained greater sensitivity (0.98 vs 0.70). Compared with that of patients with an average SLN detection number < 4, the sensitivity of patients with a SLN detection number ≥ 4 was greater (0.96 vs 0.68). Compared with hematoxylin-eosin (HE) staining, immunohistochemical (+ HE) staining showed greater sensitivity (0.99 vs 0.84). Compared with subserous injection of ICG, submucosal injection achieved greater sensitivity (0.98 vs 0.40). Compared with 5 g/L ICG, 0.5 and 0.05 g/L ICG had greater sensitivity (0.98 vs 0.83), and cT1 stage had greater sensitivity (0.96 vs 0.72) than cT2 to cT3 clinical stage. Compared with that of patients ≤ 26, the sensitivity of patients > 26 was greater (0.96 vs 0.65). Compared with the literature published before 2010, the sensitivity of the literature published after 2010 was greater (0.97 vs 0.81), and the differences were statistically significant (all P < 0.05). CONCLUSION: For the diagnosis of stomach cancer, optical imaging in conjunction with ICG-guided SLN biopsy is a therapeutically viable approach, especially for early gastric cancer. The concentration of ICG used in the SLN biopsy of gastric cancer may be too high. Moreover, NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.

In-situ monitoring of cellular H2O2 within 3D cell clusters using conductive scaffolds.

Accurately monitoring H2O2 concentrations in 3D cell clusters is challenging due to limited diffusion and rapid degradation of H2O2 in the culture medium. Despite the incorporation of three-dimensional cell culture approaches, the detection technology has largely remained as a 2D planar system. In this study, we present a versatile approach of 3D electrochemical sensing utilizing carbon nanotubes as conductive scaffolds for in-situ monitoring of H2O2 in cell clusters. These scaffolds enabled direct contact between H2O2 released from cells and the electrodes, thereby improving sensitivity and ensuring biocompatibility for cell aggregates. The scaffolds exhibited electrocatalytic behavior with a limit of detection of 6.7 nM H2O2. Additionally, the electrochemical responses of cell clusters with the scaffolds exhibited significantly higher current compared to clusters without scaffolds when stimulated with model drugs. This study underscores the potential of conductive scaffolds for real-time monitoring of H2O2 released from cell clusters in 3D microenvironments.

Seeing the unseen boundary behind you: Predicting the out-of-bounds of flick serves in playing badminton doubles.

Previous research on affordance perception has shown that elite athletes can relate the environmental features to their motor abilities to detect the opportunities for action. In playing badminton doubles, experienced players can often anticipate whether a flick serve will go out-of-bounds or not. A field study was performed to examine if such an ability was associated with a developed affordance perception. Twenty-two players with and without badminton playing experience were asked to play a receiver on court to judge without looking back whether a flick serve was out-of-bounds in both standing and retreating conditions. Forty flick serves were randomly delivered to either inner or outer rear corner of the receiver's box and land adjacent to the back service line. Each player's ability to reach high and retreat backward with a racquet was assessed on court. The results showed that predictions were better in the inner direction than the outer direction, but experienced players were more sensitive and conservative overall. Playing experience appeared to be a consistent predictor for judgment accuracy. In identifying the affordance information that could have been utilized by players for accurate predictions, only experienced players demonstrated the ability to utilize both body-scaled and action-scaled affordances effectively and reliably for better predictions in both standing and retreating conditions.

Mitigation of malondialdehyde-induced protein lipoxidation by epicatechin in whey protein isolate.

Malondialdehyde (MDA) can induce lipoxidation in whey protein isolate (WPI). The physicochemical changes in this reaction with or without the presence of a phenolic compound epicatechin (EC) were characterized in this study. Results suggested the content of MDA was significantly reduced during co-incubation of MDA and EC. The addition of EC dose-dependently alleviated MDA-induced protein carbonylation, Schiff base formation and loss of tryptophan fluorescence. The interruption of MDA-binding to WPI was directly visualized by immunoblotting analysis. Observation of the surface microstructure of WPI showed that MDA-induced protein aggregation was partially restored by EC. Meanwhile, EC was found to promote loss of both protein sulfhydryls and surface hydrophobicity due to possible phenol-protein interactions. These observations suggested the potential of EC in the relief of MDA-mediated protein lipoxidation.

Rational design and application of broad-spectrum antibodies for Bt Cry toxins determination.

Using the amino acid sequences and analysis of selected known structures of Bt Cry toxins, Cry1Ab, Cry1Ac, Cry1Ah, Cry1B, Cry1C and Cry1F we specifically designed immunogens. After antibodies selection, broad-spectrum polyclonal antibodies (pAbs) and monoclonal antibody (namely 1A0-mAb) were obtained from rabbit and mouse, respectively. The produced pAbs displayed broad spectrum activity by recognizing Cry1 toxin, Cry2Aa, Cry2Ab and Cry3Aa with half maximal inhibitory concentration (IC50) values of 0.12-9.86 µg/mL. Similarly, 1A0-mAb showed broad spectrum activity, recognizing all of the above Cry protein (IC50 values of 4.66-20.46 µg/mL) with the exception of Cry2Aa. Using optimizations studies, 1A10-mAb was used as a capture antibody and pAbs as detection antibody. Double antibody sandwich enzyme-linked immunosorbent assays (DAS-ELISAs) were established for Cry1 toxin, Cry2Ab and Cry3Aa with the limit of detection (LOD) values of 2.36-36.37 ng/mL, respectively. The present DAS-ELISAs had good accuracy and precisions for the determination of Cry toxin spiked tap water, corn, rice, soybeans and soil samples. In conclusion, the present study has successfully obtained broad-spectrum pAbs and mAb. Furthermore, the generated pAbs- and mAb-based DAS-ELISAs protocol can potentially be used for the broad-spectrum monitoring of eight common subtypes of Bt Cry toxins residues in food and environmental samples.

Effects of family life cycle events on individual Body Mass Index trajectories: Evidence from China.

PURPOSE: Body mass index (BMI) is an important predictor of one's physiological health. China is a family-centric nation compared to Western societies and has already entered an aged society. Exploring the characteristics and patterns of BMI changes during household events in China provides critical insights into the biological and social determinants of health, which can help enhance the scientific validity of health promotion measures and contribute to the realization of healthy aging goals in China. METHODS: Using data from the China Health and Nutrition Survey (CHNS) from 1993 to 2015, this article utilizes two-level growth curve models with piecewise spline specifications for age to examine the effects of family life cycle events on BMI trajectories for age groups and gender differences. RESULTS: Compared to continuing status, experiencing transition in an individual's family life cycle could lead to more fluctuating variations in their BMI trajectories, generally, there is a faster increase in BMI during youth and a faster decline during old age. As for gender heterogeneity, males are more affected by divorce, widowhood, and empty nest, whereas females' BMI changes are influenced by entering/maintaining marriage and parenthood. CONCLUSIONS: A long-term perspective has revealed the significance of family events on BMI throughout the life course. Future research should focus on the nutrition and health of specific populations, especially elderly individuals in vulnerable groups.

Unanticipated mid-flight external trunk perturbation increased frontal plane ACL loading variables during sidestep cuttings.

Unanticipated trunk perturbation is commonly observed when anterior cruciate ligament (ACL) injuries occur during direction-changing manoeuvres. This study aimed to quantify the effect of mid-flight medial-lateral external trunk perturbation directions/locations on ACL loading variables during sidestep cuttings. Thirty-two recreational athletes performed sidestep cuttings under combinations of three perturbation directions (no-perturbation, ipsilateral-perturbation, and contralateral-perturbation relative to the cutting leg) and two perturbation locations (upper-trunk versus lower-trunk). The pushing perturbation was created by customised devices releasing a slam ball to contact participants near maximum jump height prior to cutting. Perturbation generally resulted in greater peak vertical ground reaction force and slower cutting velocity. Upper-trunk contralateral perturbation showed the greatest lateral trunk bending away from the travel direction, greatest peak knee flexion and abduction angles, and greatest peak internal knee adduction moments compared to other conditions. Such increased ACL loading variables were likely due to the increased lateral trunk bending and whole-body horizontal velocity away from the cutting direction caused by the contralateral perturbation act at the upper trunk. The findings may help understand the mechanisms of indirect contact ACL injuries and develop effective cutting techniques for ACL injury prevention.

The Metabolic Functional Feature of Gut Microbiota in Mongolian Patients with Type 2 Diabetes.

The accumulating evidence substantiates the indispensable role of gut microbiota in modulating the pathogenesis of type 2 diabetes. Uncovering the intricacies of the mechanism is imperative in aiding disease control efforts. Revealing key bacterial species, their metabolites and/or metabolic pathways from the vast array of gut microorganisms can significantly contribute to precise treatment of the disease. With a high prevalence of type 2 diabetes in Inner Mongolia, China, we recruited volunteers from among the Mongolian population to investigate the relationship between gut microbiota and the disease. Fecal samples were collected from the Volunteers of Mongolia with Type 2 Diabetes group and a Control group, and detected by metagenomic analysis and untargeted metabolomics analysis. The findings suggest that Firmicutes and Bacteroidetes phyla are the predominant gut microorganisms that exert significant influence on the pathogenesis of type 2 diabetes in the Mongolian population. In the disease group, despite an increase in the quantity of most gut microbial metabolic enzymes, there was a concomitant weakening of gut metabolic function, suggesting that the gut microbiota may be in a compensatory state during the disease stage. ß-Tocotrienol may serve as a pivotal gut metabolite produced by gut microorganisms and a potential biomarker for type 2 diabetes. The metabolic biosynthesis pathways of ubiquinone and other terpenoid quinones could be the crucial mechanism through which the gut microbiota regulates type 2 diabetes. Additionally, certain Clostridium gut species may play a pivotal role in the progression of the disease.

Patterning and folding of intestinal villi by active mesenchymal dewetting.

Tissue folds are structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, finger-like protrusions that enable nutrient absorption. However, the molecular and mechanical processes driving villus morphogenesis remain unclear. Here, we identify an active mechanical mechanism that simultaneously patterns and folds the intestinal epithelium to initiate villus formation. At the cellular level, we find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. This symmetry-breaking process requires altered cell and extracellular matrix interactions that are enabled by matrix metalloproteinase-mediated tissue fluidization. Computational models, together with in vitro and in vivo experiments, revealed that these cellular features manifest at the tissue level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active dewetting of a thin liquid film.

Dynamic influence of maternal education on height among Chinese children aged 0-18 years.

Background: Maternal education is one of key factors affecting nurturing environment which significantly impacts children's height levels throughout their developmental stages. However, the influence of maternal education on children's height is less studied. This study aims to investigate the dynamic influence of maternal education on children's height among Chinese children aged 0-18 years. Methods: Children undergoing health examinations from January 2021 to September 2023 were included in this study. Clinical information including height, weight, maternal pregnancy history, blood specimens for bone metabolism-related indicators and maternal education level was collected. Children's height was categorized into 14 groups based on age and gender percentiles, following WHO 2006 growth standards. One-way analysis of variance (ANOVA), linear regression, chi-square test and Fisher's exact test were applied for data analysis. Results: A total of 6269 samples were collected, including 3654 males and 2615 females, with an average age of 8.38 (3.97) for males and 7.89 (3.55) for females. Significant correlations between maternal education level, birth weight, birth order, weight percentile, vitamin D, serum phosphorus, alkaline phosphatase levels, and children's height were identified. Birth weight's influence on height varied across age groups. Compared with normal birth weight children, low birth weight children exhibited catch-up growth within the first 6 years and a subsequent gradual widening of the height gap from 6 to 18 years old. Remarkably, the impact of maternal education on height became more pronounced among children above 3-6 years old, which can mitigate the effect of low birth weight on height. Conclusion: We found that weight percentile, birth weight, birth order, bone marker levels, and maternal education level have significant effect on height. Maternal education attenuates the impact of low birth weight on height. The findings indicated that maternal education plays a consistent and critical role in promoting robust and healthy growth.

Uric acid-lowering effect of harpagoside and its protective effect against hyperuricemia-induced renal injury in mice.

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.

Two new withanolides from Physalis minima L.

Two new withanolides named physaminilides L (1) and M (2), together with four known ones (3-6) were isolated from the Physalis minima L. The structures were established by analysis of the HR ESIMS, IR and NMR spectroscopic data. The absolute configurations were determined through NOESY and ECD spectra. For compounds 1-5 assayed at 20 µM and compound 6 at 10 µM, inhibition rates of hepatic fibrosis were 22.19%, 15.29%, 37.07%, 9.27%, 12.45%, and 37.03%, respectively.

Ultra-processed food consumption and chronic kidney disease risk: a systematic review and dose-response meta-analysis.

Background: High intake of ultra-processed food (UPF) has been associated with increased risk of chronic kidney disease(CKD), but the results remain inconsistent. We therefore performed this systematic review and dose­response meta-analysis of observational studies that shed light on the association between UPF consumption and the risk of CKD. Methods: A systematic literature search of PubMed, Embase, Web of Science, Scopus and China National Knowledge Infrastructure (CNKI) databases was carried out to find the eligible articles published up to October 31, 2023. Random-effects or fixed-effects models were used to pool the relative risks(RRs) and their 95% confidence intervals (CIs).The potential sources of heterogeneity across studies were examined using the Cochran's Q test and I-square(I2). Publication bias was examined using the visual inspection of asymmetry in funnel plots and quantified by Begg's and Egger's tests. Results: Eight studies (six cohort and two cross-sectional studies) exploring the association between UPF consumption and risk of CKD, were included in the final analysis. The pooled analyses revealed that high consumption of UPF was associated with an increased risk of CKD (RR = 1.25; 95%CI: 1.09­1.42, p < 0.0001). Moreover, a 10% increase of UPF consumption was associated with a 7% higher risk of CKD (RR = 1.07; 95%CI: 1.04­1.10, p < 0.001). Dose­response analysis of all included studies showed a linear association between UPF consumption and the risk of CKD (RR = 1.02; 95%CI:0.99­1.05, Pdose­response = 0.178, Pnonlinearity = 0.843). Conclusion: Our findings indicate that high consumption of UPF is significantly associated with an increased risk of CKD. Future research with prospective design is required to confirm this positive association.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023478483, PROSPERO identifier CRD42023478483.

Discovery and preclinical development of a therapeutically active nanobody-based chimeric antigen receptor targeting human CD22.

Chimeric antigen receptor (CAR) T cell therapies targeting B cell-restricted antigens CD19, CD20, or CD22 can produce potent clinical responses for some B cell malignancies, but relapse remains common. Camelid single-domain antibodies (sdAbs or nanobodies) are smaller, simpler, and easier to recombine than single-chain variable fragments (scFvs) used in most CARs, but fewer sdAb-CARs have been reported. Thus, we sought to identify a therapeutically active sdAb-CAR targeting human CD22. Immunization of an adult Llama glama with CD22 protein, sdAb-cDNA library construction, and phage panning yielded >20 sdAbs with diverse epitope and binding properties. Expressing CD22-sdAb-CAR in Jurkat cells drove varying CD22-specific reactivity not correlated with antibody affinity. Changing CD28- to CD8-transmembrane design increased CAR persistence and expression in vitro. CD22-sdAb-CAR candidates showed similar CD22-dependent CAR-T expansion in vitro, although only membrane-proximal epitope targeting CD22-sdAb-CARs activated direct cytolytic killing and extended survival in a lymphoma xenograft model. Based on enhanced survival in blinded xenograft studies, a lead CD22sdCAR-T was selected, achieving comparable complete responses to a benchmark short linker m971-scFv CAR-T in high-dose experiments. Finally, immunohistochemistry and flow cytometry confirm tissue and cellular-level specificity of the lead CD22-sdAb. This presents a complete report on preclinical development of a novel CD22sdCAR therapeutic.

A mechanism linking ferroptosis and ferritinophagy in melatonin-related improvement of diabetic brain injury.

Ferroptosis and ferritinophagy play critical roles in various disease contexts. Herein, we observed that ferroptosis and ferritinophagy were induced both in the brains of mice with diabetes mellitus (DM) and neuronal cells after high glucose (HG) treatment, as evidenced by decreases in GPX4, SLC7A11, and ferritin levels, but increases in NCOA4 levels. Interestingly, melatonin administration ameliorated neuronal damage by inhibiting ferroptosis and ferritinophagy both in vivo and in vitro. At the molecular level, we found that not only the ferroptosis inducer p53 but also the ferritinophagy mediator NCOA4 was the potential target of miR-214-3p, which was downregulated by DM status or HG insult, but was increased after melatonin treatment. However, the inhibitory effects of melatonin on ferroptosis and ferritinophagy were blocked by miR-214-3p downregulation. These findings suggest that melatonin is a potential drug for improving diabetic brain damage by inhibiting p53-mediated ferroptosis and NCOA4-mediated ferritinophagy through regulating miR-214-3p in neurons.

PREX2 contributes to radiation resistance by inhibiting radiotherapy-induced tumor immunogenicity via cGAS/STING/IFNs pathway in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. METHODS: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models. RESULTS: PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8+ T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy. CONCLUSIONS: PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.

J-Aggregate Promoting NIR-II Emission for Fluorescence/Photoacoustic Imaging-Guided Phototherapy.

J-aggregate is a promising strategy to enhance second near-infrared window (NIR-II) emission, while the controlled synthesis of J-aggregated NIR-II dyes is a huge challenge because of the lack of molecular design principle. Herein, bulk spiro[fluorene-9,9'-xanthene] functionalized benzobisthiadiazole-based NIR-II dyes (named BSFX-BBT and OSFX-BBT) are synthesized with different alkyl chains. The weak repulsion interaction between the donor and acceptor units and the S…N secondary interactions make the dyes to adopt a co-planar molecular conformation and display a peak absorption >880 nm in solution. Importantly, BSFX-BBT can form a desiring J-aggregate in the condensed state, and femtosecond transient absorption spectra reveal that the excited states of J-aggregate are the radiative states, and J-aggregate can facilitate stimulated emission. Consequently, the J-aggregated nanoparticles (NPs) display a peak emission at 1124 nm with a high relative quantum yield of 0.81%. The efficient NIR-II emission, good photothermal effect, and biocompatibility make the J-aggregated NPs demonstrate efficient antitumor efficacy via fluorescence/photoacoustic imaging-guided phototherapy. The paradigm illustrates that tuning the aggregate states of NIR-II dye via spiro-functionalized strategy is an effective approach to enhance photo-theranostic performance.

MILIP Binding to tRNAs Promotes Protein Synthesis to Drive Triple-Negative Breast Cancer.

Patients with triple-negative breast cancer (TNBC) have a poor prognosis due to the lack of effective molecular targets for therapeutic intervention. Here we found that the long noncoding RNA (lncRNA) MILIP supports TNBC cell survival, proliferation, and tumorigenicity by complexing with transfer RNAs (tRNA) to promote protein production, thus representing a potential therapeutic target in TNBC. MILIP was expressed at high levels in TNBC cells that commonly harbor loss-of-function mutations of the tumor suppressor p53, and MILIP silencing suppressed TNBC cell viability and xenograft growth, indicating that MILIP functions distinctively in TNBC beyond its established role in repressing p53 in other types of cancers. Mechanistic investigations revealed that MILIP interacted with eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) and formed an RNA-RNA duplex with the type II tRNAs tRNALeu and tRNASer through their variable loops, which facilitated the binding of eEF1α1 to these tRNAs. Disrupting the interaction between MILIP and eEF1α1 or tRNAs diminished protein synthesis and cell viability. Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment. SIGNIFICANCE: LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors.

Challenges and opportunities in human dimensions behind cat-wildlife conflict.

Because global anthropogenic activities cause vast biodiversity loss, human dimensions research is essential to forming management plans applicable to biodiversity conservation outside wilderness areas. Engaging public participation is crucial in this context to achieve social and environmental benefits. However, knowledge gaps remain in understanding how a balance between conservation and public demands can be reached and how complicated sociocultural contexts in the Anthropocene can be incorporated in conservation planning. We examined China's nationwide conflict between free-ranging cats (owned cats that are allowed to go outdoors or homeless cats living outdoors) and wildlife to examine how a consensus between compassion and biodiversity conservation can help in decision-making. We surveyed a random sample of people in China online. Over 9000 questionnaires were completed (44.2% response). In aggregate, respondents reported approximately 29 million free-ranging owned cats and that over 5 million domestic cats per year become feral in mainland China. Respondents who were cat owners, female, and religious were more likely to deny the negative impacts of cats on wildlife and ongoing management strategies and more supportive of stray cat shelters, adoption, and community-based fund raising than nonowners, male, and nonreligious respondents (p < 0.05). Free-ranging cat ownership and abandonment occurred less with owners with more knowledge of biodiversity and invasive species than with respondents with less knowledge of these subjects (p < 0.05). We recommend that cat enthusiasts and wildlife conservationists participate in community-based initiatives, such as campaigns to keep cats indoors. Our study provides a substantially useful framework for other regions where free-ranging cats are undergoing rapid expansion.

Retos y oportunidades de las dimensiones humanas detrás del conflicto entre gatos y fauna Resumen Debido a que las actividades antropogénicas globales causan una enorme pérdida de la biodiversidad, la investigación sobre las dimensiones humanas es esencial para generar planes de manejo aplicables a la conservación de la biodiversidad fuera de las áreas silvestres. Es muy importante lograr que el público participe en este contexto para obtener los beneficios sociales y ambientales. Sin embargo, todavía existen vacíos en el conocimiento sobre cómo lograr el balance entre la conservación y las demandas públicas y cómo incorporar los contextos socioculturales complejos del Antropoceno a la planeación de la conservación. Analizamos el conflicto nacional entre los gatos libres (gatos callejeros o gatos domésticos que se les permite salir) y la fauna en China para estudiar cómo un consenso entre la compasión y la conservación de la biodiversidad puede ayudar en la toma de decisiones. Encuestamos en línea a una muestra aleatoria de personas en China. Se completaron más de 9000 cuestionarios (44.2% de respuesta). En total, los respondientes reportaron un aproximado de 29 millones de gatos libres y que más de cinco millones de gatos domésticos se vuelven ferales al año en China. Quienes respondieron y son dueños de gatos, mujeres y religiosos tuvieron la mayor probabilidad de negar los impactos negativos de los gatos sobre la fauna y de las estrategias actuales de manejo y de mostrar más apoyo por los refugios de gatos abandonados, la adopción y de la recaudación de fondos comunitaria que quienes no son dueños, no son religiosos y son hombres (p < 0.05). La propiedad de gatos libres y el abandono ocurrieron menos con los dueños con más conocimiento sobre la biodiversidad y las especies invasoras que con los respondientes con menos conocimiento sobre estos temas (p < 0.05). Recomendamos que los aficionados a los gatos y los conservacionistas de la fauna participen en las iniciativas comunitarias; por ejemplo, campañas para mantener a los gatos dentro de casa. Nuestro estudio proporciona un marco sustancialmente útil para otras regiones en donde los gatos libres se encuentran en rápida expansión.