A brain-enriched lncRNA shields cancer cells from immune-mediated killing for metastatic colonization in the brain.

Brain metastases, including prevalent breast-to-brain metastasis (B2BM), represent an urgent unmet medical need in the care of cancer due to a lack of effective therapies. Immune evasion is essential for cancer cells to metastasize to the brain tissue for brain metastasis. However, the intrinsic genetic circuits that enable cancer cells to avoid immune-mediated killing in the brain microenvironment remain poorly understood. Here, we report that a brain-enriched long noncoding RNA (BMOR) expressed in B2BM cells is required for brain metastasis development and is both necessary and sufficient to drive cancer cells to colonize the brain tissue. Mechanistically, BMOR enables cancer cells to evade immune-mediated killing in the brain microenvironment for the development of brain metastasis by binding and inactivating IRF3. In preclinical brain metastasis murine models, locked nucleic acid-BMOR, a designed silencer targeting BMOR, is effective in suppressing the metastatic colonization of cancer cells in the brain for brain metastasis. Taken together, our study reveals a mechanism underlying B2BM immune evasion during cancer cell metastatic colonization of brain tissue for brain metastasis, where B2BM cells evade immune-mediated killing in the brain microenvironment by acquiring a brain-enriched long noncoding RNA genetic feature.

Involvement of nucleus accumbens SERCA2b in methamphetamine-induced conditioned place preference.

Methamphetamine (METH) is a highly addictive psycho-stimulant that induces addictive behaviour by stimulating increased dopamine release in the nucleus accumbens (NAc). The sarco/endoplasmic reticulum calcium ion transport ATPases (SERCA or ATP2A) is a calcium ion (Ca2+) pump in the endoplasmic reticulum (ER) membrane. SERCA2b is a SERCA subtype mainly distributed in the central nervous system. This study used conditioned place preference (CPP), a translational drug reward model, to observe the effects of SERCA and SERCA2b on METH-CPP in mice. Result suggested that the activity of SERCA was significantly decreased in NAc after METH-CPP. Intraperitoneal SERCA agonist CDN1163 injection or bilateral CDN1163 microinjection in the NAc inhibited METH-CPP formation. SERCA2b overexpression by the Adeno-associated virus can reduce the DA release of NAc and inhibit METH-CPP formation. Although microinjection of SERCA inhibitor thapsigargin in the bilateral NAc did not significantly aggravate METH-CPP, interference with SERCA2b expression in NAc by adeno-associated virus increased DA release and promoted METH-CPP formation. METH reduced the SERCA ability to transport Ca2+ into the ER in SHSY5Y cells in vitro, which was reversed by CDN1163. This study revealed that METH dysregulates intracellular calcium balance by downregulating SERCA2b function, increasing DA release in NAc and inducing METH-CPP formation. Drugs that target SERCA2b may have the potential to treat METH addiction.

An Online Survey on the Relationship Between Positive Coping and Post-Traumatic Stress Symptoms (PTSS) of Medical Students in China During the COVID-19 Pandemic: The Mediating Role of Social Support.

BACKGROUND The COVID-19 pandemic has caused varying degrees of psychological stress among medical students. This research explored the post-traumatic stress symptoms (PTSS) of medical students in China and their relationship with positive coping and social support. MATERIAL AND METHODS In the form of cross-sectional online survey, 2280 medical students locked down at home were selected by random cluster method to investigate social support, coping style, and PTSS using the Social Support Rating Scale (SSRS), Simplified Coping Style Questionnaire (SCSQ), and Post-traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), respectively. RESULTS This research found that the PTSS detection rate in medical students was 10.42% during the COVID-19 pandemic. The PTSS scores of females were significantly higher than that of the males. However, the PTSS detection rate in females (9.71%) was not significantly different from that in males (11.24%). Compared with those of the non-PTSS group, the total score and its all-factor score of social support, the total score of coping style and the positive coping score of the PTSS group were much lower, while the negative coping score of the PTSS group was much higher (P<0.01). Positive coping was positively correlated with social support, while positive coping and social support were negatively correlated with PTSS. The total effect of positive coping on PTSS was -0.310 (P<0.001), the direct effect was -0.128 (P<0.01), and the indirect effect was -0.182 (P<0.001). Social support played a mediating role between positive coping and PTSS, with the mediating effect accounting for 58.81% of the total effect. CONCLUSIONS Social support plays a mediating role between positive coping and post-traumatic stress symptoms. Objective support and positive coping are the 2 main protective factors of PTSS.

Btk knockout attenuates the liver inflammation in STZ-induced diabetic mice by suppressing NLRP3 inflammasome activation.

Btk has pro-inflammatory role through a variety of signaling pathways. NLRP3 inflammasome plays a central role in liver inflammation for mediating the secretion of pro-inflammatory mediators. However, it is still unknown whether Btk could regulate NLRP3 inflammasome activation in diabetic liver. In this study, we used Btk knockout mice to establish the diabetic model by STZ. We found that Btk knockout could alleviate diabetic liver injury. This protection was due to reduced liver inflammation rather than lipid metabolism. Moreover, we found that macrophage infiltration and pro-inflammatory mediators were both significantly increased in diabetic mice liver. However, Btk deletion could reduce the activation of macrophage and secretion of pro-inflammatory cytokine, and reduced the liver inflammation through suppressing NLRP3 inflammasome activation. In conclusion, our study demonstrated that Btk knockout could significantly attenuate liver inflammation in diabetic mice by down-regulating NLRP3 inflammasome activation. Our finding has a broad prospect and provide a new idea for the treatment of diabetic liver injury.

Inhibition of hypertrophic scar formation with oral asiaticoside treatment in a rabbit ear scar model.

Hypertrophic scar (HS) is a fibrotic skin disease characterised by over-productive collagen and excessive inflammatory reaction, which can be functionally and cosmetically problematic. A scar-prone constitute will accelerate HS formation and functional disorder, which deserves systemic therapy with oral medicine. To examine the oral therapeutic effectiveness on HS with convincing evidence of gross view and histological improvement, a rabbit ear HS model was employed with oral administration of asiaticoside (AS) at the doses of 12 and 24 mg kg-1 d-1 daily for 60 consecutive days. Gross observation and histological findings showed that oral AS treatment could significantly inhibit HS formation in a dose dependent manner. Semi-quantification of scar elevation index at days 7, 15, 30, and 60, and quantitative polymerase chain reaction at days 30 and 60 also provided the evidences of reduced scar thickness and inhibited fibrotic gene expressions of collagens I, III, TGF-ß1, interleukins 1ß, 6 and 8, and enhanced gene expression of SMAD 7 and PPAR-γ with a dose-dependent manner. These results indicated that AS is likely to serve as a systemic therapeutic agent of HS treatment for those who may have scar-prone constitute via anti-inflammation, inhibiting fibrotic process, and enhancing matrix degradation.

Lanthanide-Based Metal-Organic Frameworks Containing "V-Shaped" Tetracarboxylate Ligands: Synthesis, Crystal Structures, "Naked-Eye" Luminescent Detection, and Catalytic Properties.

Three lanthanide-based metal-organic frameworks, [Tb(HMDIA)(H2O)3]·H2O (Tb-MDIA), [Ho(HMDIA)(H2O)3]·(H2O)2 (Ho-MDIA), and [Nd(HMDIA)(H2O)3]·(H2O)2 (Nd-MDIA) from the same V-shaped ligand 5,5'-methylenediisophthalic acid (H4MDIA), were prepared by mixing Ln3+ and H4MDIA under solvothermal conditions. The crystal structures of the three complexes were determined by single-crystal X-ray diffraction. The different coordination modes of the organic ligands resulted in different framework structures among the three complexes. The luminescent properties of Ln-MDIA in the ultraviolet-visible region were also studied. Interestingly, the bright-green emitter Tb-MDIA showed high selectivity and sensitivity to allow the naked-eye visualization of Fe3+ ions and picric acid (PA) explosive, and both sensing mechanisms were revealed. Finally, Ho-MDIA and Nd-MDIA were shown to work as heterogeneous catalysts for the cyanosilylation reaction of aromatic aldehydes, and the catalysts could be recycled at least three times without any decrease in activity.

Highly Efficient Visible-Light-Driven H2 Production via an Eosin Y-Based Metal-Organic Framework.

A simple and effective strategy was developed to immobilize ecofriendly dye inside a porous metal-organic framework (MOF) built from Eosin Y with [Cd2(COO)2(µ2-H2O)] secondary building units for the first time. The MOF exhibited efficient photocatalytic activity for H2 evolution under visible-light irradiation with a turnover number of 13920 and an initial turnover frequency of 7433 h-1, which was approximately 31 times the photocatalytic efficiency of Eosin Y.

The impact of advanced proteomics in the search for markers and therapeutic targets of bladder cancer.

Bladder cancer is the most common cancer of the urinary tract and can be avoided through proper surveillance and monitoring. Several genetic factors are known to contribute to the progression of bladder cancer, many of which produce molecules that serve as cancer biomarkers. Blood, urine, and tissue are commonly analyzed for the presence of biomarkers, which can be derived from either the nucleus or the mitochondria. Recent advances in proteomics have facilitated the high-throughput profiling of data generated from bladder cancer-related proteins or peptides in parallel with high sensitivity and specificity, providing a wealth of information for biomarker discovery and validation. However, the transmission of screening results from one laboratory to another remains the main disadvantage of these methods, a fact that emphasizes the need for consistent and standardized procedures as suggested by the Human Proteome Organization. This review summarizes the latest discoveries and progress of biomarker identification for the early diagnosis, projected prognosis, and therapeutic response of bladder cancer, informs the readers of the current status of proteomic-based biomarker findings, and suggests avenues for future work.

Hepatoprotective effect of peony total glucosides and the underlying mechanisms in diabetic rats.

CONTEXT: Total glucosides of peony (TGP), compounds extracted from the dried roots of Paeonia lactiflora Pall, have been reported to have anti-inflammatory and antioxidative activities. However, the protective effect of TGP on liver injury and the underlying mechanisms remains unknown in diabetic rats. OBJECTIVES: Current study investigates prevention of liver injury by TGP in diabetic rats and its mechanism was related to the inhibition of endoplasmic reticulum stress (ERS). MATERIALS AND METHODS: Fifty adult male rats were randomly divided into: Normal group, diabetic group, TGP (50, 100 and 200 mg/kg/day) treatment groups (n = 10 per group). At the end of the 8th week, the liver was removed for biochemical and histological examinations. RESULTS: Compared with the diabetic group, administration of TGP at doses of 50, 100 and 200 mg/kg significantly prevented the increase of hepatic fibrosis score (ED50 139.4 mg/kg). Compared with diabetic group, TGP at doses of 50, 100 and 200 mg/kg showed an inhibition on the increased macrophage infiltration. MCP-1 and TNF-α mRNA and protein expression were significantly increased in diabetic group compared with normal group; TGP administration caused significant reduction of high levels of MCP-1 and TNF-α mRNA as well as protein levels. Also, TGP at all doses showed an inhibition on the increased GRP78 levels, p-Perk levels and p-Eif2α levels in liver from diabetic group. DISCUSSION AND CONCLUSIONS: Our results indicate that TGP has potential as a treatment for diabetic liver injury attenuating liver lipid accumulation and inflammation as well as ERS induced by diabetic condition.

Growth Differentiation Factor-9 Promotes Fibroblast Proliferation and Migration in Keloids through the Smad2/3 Pathway.

BACKGROUND: Keloids are fibroproliferative scars that develop as a result of a dysregulated wound healing process; however, the molecular mechanisms of keloid pathogenesis remain unclear. Keloids are characterized by the ability to spread beyond the original boundary of the wound, and they represent a significant clinical challenge. Previous work from our group suggested that growth differentiation factor (GDF)-9 plays a role in the invasive behavior of keloids. Here, we examined the involvement of GDF-9 in keloid formation and spread and elucidated a potential underlying mechanism. METHODS: The expression of GDF-9, cyclooxygenase (COX)-2, vascular epidermal growth factor (VEGF)-C, matrix metalloprotease (MMP)-2, MMP-9, transforming growth factor (TGF)-ß1, and the related signaling pathway components in human keloid tissues or keloid fibroblasts (kFBs) was monitored by qRT-PCR and western blot. A series of overexpression and silencing experiments in normal and keloid fibroblasts were used to modify the expression of GDF-9. The effects of GDF-9 on kFB proliferation and migration were assessed using the CCK-8, cell cycle and scratch wound healing assays. RESULTS: GDF-9 promotes fibroblast proliferation and migration. GDF-9 silencing in kFBs decreased cell proliferation, blocked cell cycle progression, downregulated the angiogenic markers COX-2 and VEGF-C, and downregulated MMP-2 and MMP-9 expression, whereas it had no effect on the levels of TGF-ß1. GDF-9 silencing significantly inhibited Smad2 and Smad3 phosphorylation in kFBs. CONCLUSIONS: GDF-9 promotes the proliferation and migration of kFBs via a mechanism involving the Smad2/3 pathway.

Downregulated ECRG4 is associated with poor prognosis in renal cell cancer and is regulated by promoter DNA methylation.

Esophageal cancer-related gene 4 (ECRG4) has been proposed as a putative tumor suppressor gene in several tumors. However, the role and regulation of ECRG4 in the pathogenesis of human renal cancer remain largely unknown. Our current study revealed that expression of ECRG4 is downregulated in renal cell lines and renal cancer tissues. ECRG4 expression was significantly associated with histological grade of tumors (p < 0.001), primary tumor stage (p = 0.017), and distant metastasis (p = 0.017). Low expression of ECRG4 was an independent prognostic indicator for survival of renal cancer patients. Silencing of ECRG4 expression in renal cell lines was associated with its promoter methylation. Moreover, ectopic expression of ECRG4 markedly inhibited cell proliferation and invasion in renal cancer cell lines. These results indicated that ECRG4 is frequently silenced by the methylation of promoter in renal cell cancers. ECRG4 may be a tumor suppressor in renal cancer and serve as a prognostic marker.

Hierarchical Porous Polystyrene Monoliths from PolyHIPE.

Hierarchical porous polystyrene monoliths (HCP-PolyHIPE) are obtained by hypercrosslinking poly(styrene-divinylbenzene) monoliths prepared by polymerization of high internal phase emulsions (PolyHIPEs). The hypercrosslinking is achieved using an approach known as knitting which employs formaldehyde dimethyl acetal (FDA) as an external crosslinker. Scanning electron microscopy (SEM) confirms that the macroporous structure in the original monolith is retained during the knitting process. By increasing the amount of divinylbenzene (DVB) in PolyHIPE, the BET surface area and pore volume of the HCP-PolyHIPE decrease, while the micropore size increases. BET surface areas of 196-595 m(2) g(-1) are obtained. The presence of micropores, mesopores, and macropores is confirmed from the pore size distribution. With a hierarchical porous structure, the monoliths reveal comparable gas sorption properties and potential applications in oil spill clean-up.

Efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in the treatment of recurrent ovarian cancer: A systematic review and meta-analysis.

BACKGROUND: Recurrent ovarian cancer (OC) presents a significant therapeutic challenge with limited treatment success. Programmed cell death protein 1 (PD-1/PD-L1) immune checkpoint inhibitors have emerged as a potential treatment avenue, necessitating a systematic review and meta-analysis to evaluate their efficacy and safety. METHODS: Adhering to preferred reporting items for systematic reviews and meta-analyses guidelines, we conducted a comprehensive literature search across PubMed, Embase, Web of Science, and Cochrane Library, culminating in the inclusion of studies focusing on the treatment of recurrent OC with PD-1/PD-L1 inhibitors. Studies were evaluated using the Newcastle-Ottawa Scale and analyzed using fixed or random effects models depending on heterogeneity levels. RESULTS: Our search yielded 1215 articles, with 6 meeting the inclusion criteria for final analysis. Studies varied in size and reported median age, overall survival (OS), progression-free survival (PFS), and adverse events. The meta-analysis showed improved Objective Response Rates (ORR), Disease Control Rate (DCR), and PFS in patients treated with PD-1/PD-L1 inhibitors. The overall adverse event rate was 17.9%, indicating a need for careful patient selection and monitoring. No significant publication bias was detected, enhancing the reliability of our findings. CONCLUSIONS: PD-1/PD-L1 inhibitors offer a promising treatment option for recurrent OC, improving ORR, DCR, and PFS. However, the higher incidence of adverse events necessitates a cautious approach to their use. Future research should focus on long-term outcomes, biomarker identification, and optimal combination therapies.

Health condition and socioeconomic status mediate the causal effect of reproductive traits on nonalcoholic fatty liver disease: evidence from Mendelian randomization study.

Background: Observational data posits a correlation between reproductive traits and nonalcoholic fatty liver disease (NAFLD), but their causal inference is still unclear. This investigation seeks to elucidate the causal influence of reproductive traits on NAFLD and determine the intervening role of health condition and socioeconomic status in these connections. Methods: Utilizing a Mendelian Randomization (MR) approach, this research leveraged a comprehensive dataset from the Genome-wide Association Study (GWAS) database. The study incorporated body mass index, major depression, educational level, household income and Townsend deprivation index as intermediary variables. Initially, a bidirectional two-sample MR study was conducted to explore the genetic associations between reproductive traits and NAFLD. Then, two-step MR analyses were implemented to quantify the extent of mediation by these indicators. The weighted inverse variance method was the primary analytical approach, complemented by several sensitivity analyses to affirm the robustness of the MR assumptions. Finally, these findings were validated in the FinnGen research. Results: The bidirectional MR analysis indicated that earlier reproductive traits (age at menarche, age at first sexual intercourse, and age at first birth) were associated with an elevated risk of NAFLD, absent any evidence of the reverse relationship. Body mass index accounted for 35.64% of the association between premature menarche and NAFLD. Additionally, body mass index, major depression, educational level and household income mediated 41.65%, 14.35%, 37.88%, and 18.59% of the connection between early sexual intercourse and NAFLD, respectively. Similarly, these same variables elucidated 36.36%, 15.58%, 41.56%, and 22.73% of the correlation between younger age at first birth and NAFLD. Conclusion: Our study elucidated the causal relationships between reproductive traits and NAFLD. Potential underlying mechanisms may involve factors such as body mass index, major depression, educational attainment and household income.

Comparison of long-term survival of neoadjuvant therapy plus surgery versus upfront surgery and the role of adjuvant therapy for T1b-2N0-1 esophageal cancer: a population study of the SEER database and Chinese cohort.

BACKGROUND: For stage T1b-2N0-1 esophageal cancer, the impact of neoadjuvant therapy plus surgery (NS), surgery alone (SA), and surgery plus adjuvant therapy (ST) on cancer-specific survival (CSS) and overall survival (OS) is uncertain. METHODS: Stage T1b-2N0-1 esophageal cancer patients from the SEER database and two Chinese cancer centers were included in this study. The Kaplan-Meier method was used to plot survival curves, which were compared using the log-rank test. Propensity score matching was used to equalize differences between the groups. Cox proportional hazards regression models were used to analyze prognostic factors. A nomogram for OS was developed after screening the variables using the Cox proportional hazards regression model and the least absolute shrinkage and selection operator. The performance of the nomogram was assessed by the Harrell concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic curve, calibration plots, and decision curve analysis. RESULTS: After propensity score matching analysis, the 3-year CSS and OS rates in the NS group compared to the SA group were 80.3% versus 62.1% (P=0.016) and 75.8% versus 55.5% (P=0.006), the 3-year CSS and OS rates in the NS group compared to the ST group were 71.3% versus 68.3% (P=0.560) and 69.8% versus 62.9% (P=0.330), the 3-year CSS and OS rates in the SA group compared to the ST group were 54.6% versus 66.7% (P=0.220) and 50.2% versus 57.9% (P=0.290), respectively. The predictive nomogram for OS in T1b-2N0-1 patients ultimately incorporated five clinicopathological variables: T stage, N stage, age, examined lymph nodes , and therapy modality. The nomogram C-index for predicting OS was 0.648, 0.663, and 0.666 in the training group, external validation group-1, and external validation group-2, respectively. The 1-, 3-, and 5-year predicted AUC values of the OS prediction model were 0.659, 0.639, and 0.612 for the training group, and 0.786, 0.758, and 0.692 for validation group-1, and 0.805, 0.760, and 0.693 for validation group-2, respectively. CONCLUSION: For patients with stage T1b-2N0-1 esophageal cancer, neoadjuvant therapy significantly improves prognosis compared to surgery alone, those presenting with positive lymph nodes after upfront surgery can achieve survival benefits from adjuvant therapy.

MiR-3682-3p promotes esophageal cancer progression by targeting FHL1 and activating the Wnt/ß-catenin signaling pathway.

BACKGROUND: Esophageal cancer (EC) is highly ranked among all cancers in terms of its incidence and mortality rates. MicroRNAs (miRNAs) are considered to play key regulatory parts in EC. Multiple research studies have indicated the involvement of miR-3682-3p and four and a half LIM domain protein 1 (FHL1) in the achievement of tumors. The aim of this research was to clarify the significance of these genes and their possible molecular mechanism in EC. METHODS: Data from a database and the tissue microarray were made to analyze the expression and clinical significance of miR-3682-3p or FHL1 in EC. Reverse transcription quantitative PCR and Western blotting were used to detect the expression levels of miR-3682-3p and FHL1 in EC cells. CCK8, EdU, wound healing, Transwell, flow cytometry, and Western blotting assays were performed to ascertain the biological roles of miR-3682-3p and FHL1 in EC cells. To confirm the impact of miR-3682-3p in vivo, a subcutaneous tumor model was created in nude mice. The direct interaction between miR-3682-3p and FHL1 was demonstrated through a luciferase assay, and the western blotting technique was employed to assess the levels of crucial proteins within the Wnt/ß-catenin pathway. RESULTS: The noticeable increase in the expression of miR-3682-3p and the decrease in the expression of FHL1 were observed, which correlated with a negative impact on the patients' overall survival. Upregulation of miR-3682-3p expression promoted the growth and metastasis of EC, while overexpression of FHL1 partially reversed these effects. Finally, miR-3682-3p motivates the Wnt/ß-catenin signal transduction by directly targeting FHL1. CONCLUSION: MiR-3682-3p along the FHL1 axis activated the Wnt/ß-catenin signaling pathway and thus promoted EC malignancy.

Predictive role of impulsivity, anxiety, and depression in the efficacy of intermittent theta burst transcranial magnetic stimulation modalities for treating methamphetamine use disorder: A randomized clinical trial.

INTRODUCTION: Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. METHODS: Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. CONCLUSIONS: iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.

Integrative single-cell sequencing analysis distinguishes survival-associated cells from the breast cancer microenvironment.

BACKGROUND: Breast cancer shows a highly complex tumor microenvironment by containing various cell types. Identifying prognostic cell populations in the tumor microenvironment will improve the mechanistical understanding of breast cancer and facilitate the development of new breast cancer therapies by targeting the tumor microenvironment. The development of single-cell sequencing reveals various cell types, states, and lineages within the context of heterogenous breast tumors, but identifying phenotype-associated subpopulations is challenging. RESULTS: Here, we applied Scissor (single-cell identification of subpopulations with bulk Sample phenotype correlation) to integrate single cell and bulk data of breast cancer, and found that MHC-deficient tumor cells, FABP5+ macrophages, and COL1A1+ cancer-associated fibroblasts (CAFs) were detrimental to patient survival, while T cells and dendritic cells were the main protective cells. MHC-deficient tumor cells show strong downregulation of MHC expression for immune evasion by downregulating interferon and JAK-STATs signaling. FABP5+ macrophages show low antigen-presenting activity via associating with lipid metabolism. Our data suggest that COL1A1+ CAFs may block T-cell immune infiltration through cell interaction in breast tumor microenvironment. CONCLUSION: Taken together, our study reveals survival-associated subpopulations in breast tumor microenvironment. Importantly, subpopulations related to immune evasion of breast cancer is uncovered.

The Prognosis of Patients Tested Positive for Stenotrophomonas maltophilia from Different Sources.

Purpose: The purpose of this study was to analyze the prognosis of patients tested positive for Stenotrophomonas maltophilia (SMA) from different sources. Methods: A retrospective study was conducted among 651 patients tested positive for SMA from January 2020 to October 2022 in the First Affiliated Hospital of Anhui Medical University. The patients were divided into seven groups by the source of SMA. Univariate and multivariate analyses were used to identify risk factors for mortality in patients tested positive for SMA from different sources. Results: A total of 651 SMA isolates were collected from various sources, including sputum (348 isolates, 53%), bronchoalveolar lavage fluid (52, 8%), abdominal drainage fluid (76, 12%), wound secretion (66, 10%), blood (62, 10%), urine (41, 6%) and cerebrospinal fluid (6, 1%). Compared with other groups, the mortality of the patients in the bronchoalveolar lavage fluid culture group, blood culture group, and abdominal drainage fluid culture group was higher, at 40.38%, 32.26%, and 26.32%, respectively. Multivariate analysis showed that continuous renal replacement therapy was an independent risk factor for mortality in patients with SMA bloodstream infection (P=0.020, OR=6.86), and effective antimicrobial therapy after being positive for S. maltophilia isolates (P=0.002, OR=0.10) was negatively correlated with the death of patients with SMA bloodstream infection. Age ≥65 years (P= 0.043, OR=4.96), kidney disease (P=0.045, OR=4.62) and antifungal agent exposure (P=0.036, OR=5.13) were independent risk factors for mortality in patients with SMA intra-abdominal infection. Antifungal agent exposure (P=0.024, OR=0.51) and glycopeptide exposure (P=0.045, OR=0.53) were independent risk factors for mortality in patients in the sputum culture group. Conclusion: SMA has a high rate of antimicrobial resistance and can cause multisite infection. Pulmonary infections, bloodstream infections and abdominal infections caused by SMA have high mortality, and timely standardized treatment can reduce mortality.

Circ_0011385 knockdown inhibits cell proliferation, migration and invasion, whereas promotes cell apoptosis by regulating miR-330-3p/MYO6 axis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor. Recent studies have showed circular RNA (circRNA) participates in the development of CRC. The study was designed to reveal the role of circ_0011385 in CRC progression and underneath mechanism. METHODS: The expression circ_0011385, microRNA-330-3p (miR-330-3p) and myosin VI (MYO6) mRNA were determined by quantitative real-time polymerase chain reaction. Protein expression was detected by Western blot assay. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), cell colony formation and flow cytometry assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by wound-healing assay and transwell invasion assay, respectively. The binding sites between miR-330-3p and circ_0011385 or MYO6 were predicted by CircInteractome or starBase online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. RESULTS: Circ_0011385 and MYO6 expression were dramatically upregulated, while miR-330-3p expression was downregulated in CRC tissues or cells compared with control groups. Circ_0011385 expression was associated with tumor size, tumor-node-metastasis stage (TNM) stage and lymph node metastasis of CRC patients. Circ_0011385 silencing or MYO6 absence repressed cell proliferation, migration and invasion, whereas induced cell apoptosis in CRC. Additionally, miR-330-3p inhibitor or MYO6 overexpression attenuated the repressive impacts of circ_0011385 silencing on CRC process. Circ_0011385 was associated with miR-330-3p, and miR-330-3p targeted MYO6. Circ_0011385 knockdown inactivated MEK1/2/ERK1/2 signaling pathway by miR-330-3p/MYO6 axis. Furthermore, circ_0011385 knockdown suppressed tumor growth in vivo. CONCLUSION: Circ_0011385 regulated CRC process by miR-330-3p/MYO6 axis through MEK1/2/ERK1/2 signaling pathway, providing a novel therapeutic target for CRC.