The impact of negative cognitive bias on NSSI: mediating non-adaptive cognitive emotion regulation strategies.

BACKGROUND: Individuals may be more likely to engage in NSSI due to negative cognitive bias, while the use of negative emotional regulation mechanisms may further contribute to NSSI. Currently, there is a dearth of studies regarding the correlation among the three variables. METHOD: The study employed convenience sampling to collect data via online platforms from a total of 572 college students in Harbin, Heilongjiang Province, China, over the period of January 2024 to February 2024. The questionnaires comprise the Non-Adaptive Cognitive Emotion Srategy Regulation Subscale, the Negative Cognitive Processing Bias Questionnaire, and the NSSI Questionnaire. OUTCOME: Negative cognitive bias significantly and directly influences NSSI, as indicated by a beta coefficient of 0.3788 and a confidence interval of [0.2878, 0.4698]. The existence of negative cognitive bias significantly enhances the impact of non-adaptive cognitive emotion control approaches (ß = 0.5613, CI [0.4808, 0.6418]). Non-adaptive cognitive emotion regulation strategies showed a significant effect on NSSI, as indicated by a beta coefficient of 0.2033 and a confidence interval of [0.0942, 0.3125]. The non-adaptive cognitive emotion control strategy serves as an intermediary between negative cognitive bias and NSSI, explaining 30.12% of the overall impact. IN CONCLUSION: The results demonstrate that non-adaptive cognitive emotion regulation strategies play a partially moderating role in the relationship between negative cognitive bias and NSSI among nursing students. We emphasize the importance of non-adaptive cognitive emotion regulation strategies, negative cognitive biases, and NSSI among nursing students. In order to reduce the occurrence of NSSI, it is important for schools, families, and teachers to work together closely and implement a well-organized and efficient intervention to protect the mental well-being of nursing students.

The pyroptosis mediated biomarker pattern: an emerging diagnostic approach for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) affects 1% of people over 60, and long-term levodopa treatment can cause side effects. Early diagnosis is of great significance in slowing down the pathological process of PD. Multiple pieces of evidence showed that non-coding RNAs (ncRNAs) could participate in the progression of PD pathology. Pyroptosis is known to be regulated by ncRNAs as a key pathological feature of PD. Therefore, evaluating ncRNAs and pyroptosis-related proteins in serum could be worthy biomarkers for early diagnosis of PD. METHODS: NcRNAs and pyroptosis/inflammation mRNA levels were measured with reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Luciferase assays were performed to confirm GSDME as a target of miR-675-5p and HMGB1 as a target of miR-1247-5p. In the serum of healthy controls (n = 106) and PD patients (n = 104), RT-qPCR was utilized to assess miR-675-5p, miR-1247-5p, and two related ncRNAs (circSLC8A1and lncH19) levels. The enzyme-linked immunosorbent assay measured serum levels of pyroptosis-related proteins in controls (n = 54) and PD patients (n = 70). RESULTS: Our data demonstrated that miR-675-5p and miR-1247-5p significantly changed in PD neuron and animal models. Overexpressed miR-675-5p or downregulated miR-1247-5p could regulate pyroptosis and inflammation in PD neuron models. Using the random forest algorithm, we constructed a classifier based on PD neuron-pyroptosis pathology (four ncRNAs and six proteins) having better predictive power than single biomarkers (AUC = 92%). Additionally, we verified the performance of the classifier in early-stage PD patients (AUC ≥ 88%). CONCLUSION: Serum pyroptosis-related ncRNAs and proteins could serve as reliable, inexpensive, and non-invasive diagnostic biomarkers for PD. LIMITATIONS: All participants were from the same region. Additionally, longitudinal studies in the aged population are required to explore the practical application value of the classifier.

Diversified molecular adaptations of inorganic nitrogen assimilation and signaling machineries in plants.

Plants evolved sophisticated machineries to monitor levels of external nitrogen supply, respond to nitrogen demand from different tissues and integrate this information for coordinating its assimilation. Although roles of inorganic nitrogen in orchestrating developments have been studied in model plants and crops, systematic understanding of the origin and evolution of its assimilation and signaling machineries remains largely unknown. We expanded taxon samplings of algae and early-diverging land plants, covering all main lineages of Archaeplastida, and reconstructed the evolutionary history of core components involved in inorganic nitrogen assimilation and signaling. Most components associated with inorganic nitrogen assimilation were derived from the ancestral Archaeplastida. Improvements of assimilation machineries by gene duplications and horizontal gene transfers were evident during plant terrestrialization. Clusterization of genes encoding nitrate assimilation proteins might be an adaptive strategy for algae to cope with changeable nitrate availability in different habitats. Green plants evolved complex nitrate signaling machinery that was stepwise improved by domains shuffling and regulation co-option. Our study highlights innovations in inorganic nitrogen assimilation and signaling machineries, ranging from molecular modifications of proteins to genomic rearrangements, which shaped developmental and metabolic adaptations of plants to changeable nutrient availability in environments.

Phylotranscriptomics unveil a Paleoproterozoic-Mesoproterozoic origin and deep relationships of the Viridiplantae.

The Viridiplantae comprise two main clades, the Chlorophyta (including a diverse array of marine and freshwater green algae) and the Streptophyta (consisting of the freshwater charophytes and the land plants). Lineages sister to core Chlorophyta, informally refer to as prasinophytes, form a grade of mainly planktonic green algae. Recently, one of these lineages, Prasinodermophyta, which is previously grouped with prasinophytes, has been identified as the sister lineage to both Chlorophyta and Streptophyta. Resolving the deep relationships among green plants is crucial for understanding the historical impact of green algal diversity on marine ecology and geochemistry, but has been proven difficult given the ancient timing of the diversification events. Through extensive taxon and gene sampling, we conduct large-scale phylogenomic analyses to resolve deep relationships and reveal the Prasinodermophyta as the lineage sister to Chlorophyta, raising questions about the necessity of classifying the Prasinodermophyta as a distinct phylum. We unveil that incomplete lineage sorting is the main cause of discordance regarding the placement of Prasinodermophyta. Molecular dating analyses suggest that crown-group green plants and crown-group Prasinodermophyta date back to the Paleoproterozoic-Mesoproterozoic. Our study establishes a plausible link between oxygen levels in the Paleoproterozoic-Mesoproterozoic and the origin of Viridiplantae.

Novel nomograms for predicting survival for immediate breast reconstruction patients diagnosed with invasive breast cancer-a single-center 15-year experience.

Background: Immediate breast reconstruction is widely accepted following oncologic mastectomy. This study aimed to build a novel nomogram predicting the survival outcome for Chinese patients undergoing immediate reconstruction following mastectomy for invasive breast cancer. Methods: A retrospective review of all patients undergoing immediate reconstruction following treatment for invasive breast cancer was performed from May 2001 to March 2016. Eligible patients were assigned to a training set or a validation set. Univariate and multivariate Cox proportional hazard regression models were used to select associate variables. Two nomograms were developed based on the training cohort for breast cancer-specific survival (BCSS) and disease-free survival (DFS). Internal and external validations were performed, and the C-index and calibration plots were generated to evaluate the performance (discrimination and accuracy) of the models. Results: The 10-year estimated BCSS and DFS were 90.80% (95% CI: 87.30%-94.40%) and 78.40% (95% CI: 72.50%-84.70%), respectively, in the training cohort. In the validation cohort, they were and 85.60% (95% CI, 75.90%-96.50%) and 84.10% (95% CI, 77.80%-90.90%), respectively. Ten independent factors were used to build a nomogram for prediction of 1-, 5- and 10-year BCSS, while nine were used for DFS. The C-index was 0.841 for BCSS and 0.737 for DFS in internal validation, and the C-index was 0.782 for BCSS and 0.700 for DFS in external validation. The calibration curve for both BCSS and DFS demonstrated acceptable agreement between the predicted and actual observation in the training and the validation cohorts. Conclusion: The nomograms provided valuable visualization of factors predicting BCSS and DFS in invasive breast cancer patients with immediate breast reconstruction. The nomograms may have tremendous potential in guiding individualized decision-making for physicians and patients in choosing the optimized treatment methods.

Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis.

BACKGROUND: Chemoresistance is the main reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Thus, there is an urgent need to screen out new targets and compounds to reverse chemotherapeutic resistance. METHODS: We established a bio-bank of human PDAC organoid models, covering a representative range of PDAC tumor subtypes. We screened a library of 1304 FDA-approved compounds to identify candidates efficiently overcoming chemotherapy resistance. The effects of the compounds were evaluated with a CellTiter-Glo-3D assay, organoid apoptosis assay and in vivo patient-derived xenograft (PDX), patient-derived organoid (PDO) and LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) genetically engineered mouse models. RNA-sequencing, genome editing, sphere formation assays, iron assays and luciferase assays were conducted to elucidate the mechanism. RESULTS: High-throughput drug screening of chemotherapy-resistant PDOs identified irbesartan, an angiotensin ‖ type 1 (AT1) receptor antagonist, which could synergistically enhance the ability of chemotherapy to kill PDAC cells. In vitro and in vivo validation using PDO, PDX and KPC mouse models showed that irbesartan efficiently sensitized PDAC tumors to chemotherapy. Mechanistically, we found that irbesartan decreased c-Jun expression by inhibiting the Hippo/YAP1 pathway and further overcame chemotherapy resistance in PDAC. We also explored c-Jun, a potential target of irbesartan, which can transcriptionally upregulate the expression of key genes involved in stemness maintenance (SOX9/SOX2/OCT4) and iron metabolism (FTH1/FTL/TFRC). More importantly, we observed that PDAC patients with high levels of c-Jun expression demonstrated poor responses to the current standard chemotherapy regimen (gemcitabine plus nab-paclitaxel). Moreover, patients with PDAC had significant survival benefits from treatment with irbesartan plus a standard chemotherapy regimen in two-center retrospective clinical cohorts and patients with high c-Jun expression exhibited a better response to combination chemotherapy. CONCLUSIONS: Irbesartan could be used in combination with chemotherapy to improve the therapeutic efficacy in PDAC patients with high levels of c-Jun expression. Irbesartan effectively inhibited chemotherapy resistance by suppressing the Hippo/YAP1/c-Jun/stemness/iron metabolism axis. Based on our findings, we are designing an investigator-initiated phase II clinical trial on the efficacy and safety of irbesartan plus a standard gemcitabine/nab-paclitaxel regimen in the treatment of patients with advanced III/IV staged PDAC and are hopeful that we will observe patient benefits.

The origin, evolution and functional divergence of HOOKLESS1 in plants.

Apical hooks are functional innovations only observed in angiosperms, which effectively protect the apical meristems out of damage during plant seedlings penetrating soil covers. Acetyltransferase like protein HOOKLESS1 (HLS1) in Arabidopsis thaliana is required for hook formation. However, the origin and evolution of HLS1 in plants are still not solved. Here, we traced the evolution of HLS1 and found that HLS1 originated in embryophytes. Moreover, we found that Arabidopsis HLS1 delayed plant flowering time, in addition to their well-known functions in apical hook development and newly reported roles in thermomorphogenesis. We further revealed that HLS1 interacted with transcription factor CO and repressed the expression of FT to delay flowering. Lastly, we compared the functional divergence of HLS1 among eudicot (A. thaliana), bryophytes (Physcomitrium patens and Marchantia polymorpha) and lycophyte (Selaginella moellendorffii). Although HLS1 from these bryophytes and lycophyte partially rescued the thermomorphogenesis defects in hls1-1 mutants, the apical hook defects and early flowering phenotypes could not be reversed by either P. patens, M. polymorpha or S. moellendorffii orthologs. These results illustrate that HLS1 proteins from bryophytes or lycophyte are able to modulate thermomorphogenesis phenotypes in A. thaliana likely through a conserved gene regulatory network. Our findings shed new light on the understanding of the functional diversity and origin of HLS1, which controls the most attractive innovations in angiosperms.

SDCBP promotes pancreatic cancer progression by preventing YAP1 from ß-TrCP-mediated proteasomal degradation.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumour with limited treatment options. Here, we identified syndecan binding protein (SDCBP), also known as syntenin1, as a novel targetable factor in promoting PDAC tumour progression. We also explored a therapeutic strategy for suppressing SDCBP expression. DESIGN: We used samples from patients with PDAC, human organoid models, LSL-KrasG12D/+mice, LSL-Trp53R172H/+ and Pdx1-Cre (KPC) mouse models, and PDX mouse models. Immunostaining, colony formation assay, ethynyl-2-deoxyuridine incorporation assay, real-time cell analysis, cell apoptosis assay, automated cell tracking, invadopodia detection and gelatin degradation assays, coimmunoprecipitation, and pull-down assays were performed in this study. RESULTS: The median overall survival and recurrence-free survival rates in the high-SDCBP group were significantly shorter than those in the low-SDCBP group. In vitro and in vivo studies have demonstrated that SDCBP promotes PDAC proliferation and metastasis. Mechanically, SDCBP inhibits CK1δ/ε-mediated YAP-S384/S387 phosphorylation, which further suppresses ß-TrCP-mediated YAP1 ubiquitination and proteasome degradation by directly interacting with YAP1. SDCBP interacts with the TAD domain of YAP1, mainly through its PDZ1 domain. Preclinical KPC mouse cohorts demonstrated that zinc pyrithione (ZnPT) suppresses PDAC tumour progression by suppressing SDCBP. CONCLUSIONS: SDCBP promotes the proliferation and metastasis of PDAC by preventing YAP1 from ß-TrCP-mediated proteasomal degradation. Therefore, ZnPT could be a promising therapeutic strategy to inhibit PDAC progression by suppressing SDCBP.

Opposing manner of miR-455-3p against NR2B-PSD-95-nNOS complex in the cortex and hippocampus of depressive rats under simulated complex space environment.

Depression in astronauts is one of the consequences of space flight effects, negatively impacting their work performances. Unfortunately, the underlying molecular mechanisms in space flight-induced depression are still unknown; however, various neuropsychiatric disorders reported that overexpressed NR2B-PSD-95-nNOS complex in the brain triggers various pathological pathways, and inhibiting NR2B-PSD-95-nNOS complex asserts antidepressant effects. Through our in silico analysis, we found that epigenetic regulator miR-445-3p targets PSD-95 and is hypothesized to down-regulate NR2B-PSD-95-nNOS complex to prevent neuronal damage associated with depression. Therefore, the present study is aimed to determine the novel insight of the miR-455-3p against the NR2B-PSD-95-nNOS complex in the neurobiology of space flight-induced depressive behavior. Using a simulated space environment complex model (SCSE) for 21 days, we induced depressive behavior in rats to analyze miR-455-3p expression and NR2B-PSD-95-nNOS complex in the cortex and hippocampus of the SCSE depressed rats through qRT-PCR and western blot analysis. Further, an in vitro microgravity model using rat hippocampus cell lines (RHNC) was utilized to identify the independent role of miR-455-3p on (1) NR2B-PSD-95-nNOS complex and TrKB-BDNF proteins, (2) oxidative stress, (3) nitric oxide level, (4) inflammatory cytokines, (5) mitochondrial biogenesis/ dynamics, and (6) cell survival. Our results showed that miR-455-3p regulates NR2B-PSD-95-nNOS complex in the SCSE depressed rats in opposite ways, with the cortex revealing a higher level of miR-455-3p and low-level NR2B-PSD-95-nNOS complex and the hippocampus showing down-regulated miR-455-3p and up-regulated NR2B-PSD-95-nNOS complex, indicating a region-specific change in the miR-455-3p and NR2B-PSD-95-nNOS complex in the SCSE depressed rats. Further RHNC results also confirmed down-regulated miR-455-3p and up-regulated NR2B-PSD-95-nNOS complex expression, similar to the findings in the hippocampus of SCSE rats, suggesting that microgravity influences miR-455-3p and associated changes. Additional investigations revealed that miR-455-3p targets PSD-95 and co-regulates NR2B-PSD-95-nNOS complex along with TrkB-BDNF signaling and exert protective effects against NR2B-PSD-95-nNOS complex, oxidative stress, nitric oxide, inflammatory cytokines, and mitochondrial defects, suggesting a valuable biomarker for devising depressive disorders.

Change in patent foramen ovale height is associated with cryptogenic stroke and the construction of a morphology-based scoring system.

Introduction: Current guidelines recommended patent foramen ovale (PFO) occlusion as the preferred treatment for PFO-related cryptogenic stroke (CS); however, finding the causative foramen ovale remains challenging. This study aimed to identify predictors and establish a scoring system by assessing PFO morphology and stroke-related factors. Methods: Based on a prospective multicenter registered clinical trial, we compared data mainly derived from transesophageal echocardiography (TEE) and clinical history in patients with PFO-related CS and those without CS (non-CS) with incidental PFO. Subsequently, we explored independent predictors using logistic analysis, established a scoring system based on the results, and finally evaluated the scoring system using receiver operating characteristic (ROC) analysis and internal validation. Results: 75 patients with PFO-related CS and 147 non-CS patients were enrolled. Multivariate logistic analysis showed that the change in PFO height, large PFO, atrial septal aneurysm (ASA), and sustained right-to-left shunt (RLS) had independent relationships with CS. Based on the odds ratio value of each independent factor, a scoring system was built: change in PFO height ≥ 1.85 mm (3 points), large PFO (2 points), ASA (5 points), sustained RLS (2 points). 0-2 points correspond to low-risk PFO, 3-5 points medium-risk PFO, and 7-12 points high-risk PFO. ROC analysis showed an area under the curve of 0.80 to predict CS. The proportion of patients with CS is increasing based on these points. Conclusions: Our study screened out the change in PFO height as an independent predictor of CS. A simple and convenient scoring system can provide constructive guidance for identifying whether the PFO is causal and consequently selecting patients more likely to benefit from closure.

A Single-Center Retrospective Analysis of Local and Distant Relapse of Breast Cancer Following Immediate Breast Reconstruction According to Molecular Subtypes.

Purpose: Concerns have been raised about the oncologic safety of immediate breast reconstruction (IBR) following mastectomy for breast cancer. This study aimed to evaluate locoregional recurrence (LRR) and distant metastasis (DM) of breast cancer according to its molecular subtype in patients who underwent mastectomy alone or IBR after mastectomy. Methods: In this retrospective cohort study, consecutive breast cancer patients treated by the single senior surgeon (XZ) between February 2010 and December 2014 were eligible. In total, 389 consecutive patients were included; 295 patients underwent mastectomy alone and 94 patients underwent mastectomy with IBR. Data were retrospectively collected and analyzed for LRR and DM stratified by molecular subtypes. Results: With a median follow-up of 73 and 87.5 months, 1.69% of patients in the mastectomy alone group developed LRR compared to 0% in the reconstruction group (p = 0.342) and the total incidence of DMs was 11.52% in patients who received mastectomy alone and 7.44% in patients who received postmastectomy IBR (p = 0.262), respectively. The cumulative incidence of LRR was 2.1% vs. 0% for luminal A, 0% vs. 0% for luminal B, 0% vs. 0% for human epidermal growth factor receptor 2 (HER2)-enriched, and 4.5% vs. 0% for triple-negative in the mastectomy alone group compared to the postmastectomy IBR group. The cumulative incidence of DM was 15.5% vs. 5.7% for luminal A, 10% vs. 8.7% for luminal B, 17.3% vs. 0% for HER2-enriched, and 6.8% vs. 7.1% for triple-negative in the mastectomy alone group compared to the postmastectomy IBR group. On multivariable Cox regression analysis, lymph node metastasis was associated with an increased risk of DM in the mastectomy alone group (p = 0.03) and neoadjuvant chemotherapy was associated with an increased risk of DM in the postmastectomy IBR group (p = 0.021). Conclusion: This study suggests that IBR does not have a negative impact on the LRR and DM of breast cancer according to molecular subtypes.

Interaction in acting training and its different manifestations in novice and professional actors.

This study aimed to identify the characteristics of interactions during acting training and the underlying intrapersonal changes evoked by a training process that emphasizes paying attention to a partner (the Meisner technique). This was operationalized by conducting a post-hoc analysis and categorizing the utterances made by novice and professional actors during acting training based on video and audio recordings. In Study 1, novice participants tended to change their way of communication as the course progressed, decreasing the number of utterances that simply described the partner's behavior and increasing those that speculated about the partner's inner state. We then used a different focus placed on the interaction, as implied by the different kinds of utterances used, to describe the divergences between novice and professional actors regarding their interaction characteristics. In Study 2, results showed that while professional actors devoted themselves more to the connection with their partner and demonstrated more balanced communication, novice actors relied on general inference to speculate about others' affective states. By comparing the characteristics of the utterances between novice and professional actors as they played different roles or made switches (i.e., changing from passive to active utterance in communication), this study suggests that an important impact of acting training on social abilities relates to its potential to increase the levels of involvement in on-going interactions.

Comparison of outcomes between immediate implantbased and autologous reconstruction: 15-year, single-center experience in a propensity score-matched Chinese cohort.

OBJECTIVE: The number of immediate breast reconstruction (IBR) procedures has been increasing in China. This study aimed to investigate the oncological safety of IBR, and to compare the survival and surgical outcomes between implant-based and autologous reconstruction. METHODS: Data from patients diagnosed with invasive breast cancer who underwent immediate total breast reconstruction between 2001 and 2016 were retrospectively reviewed. Long-term breast cancer-specific survival (BCSS), disease-free survival (DFS), and locoregional recurrence-free survival (LRFS) were evaluated. Patient satisfaction with the breast was compared between the implant-based and autologous groups. BCSS, DFS, and LRFS were compared between groups after propensity score matching (PSM). RESULTS: A total of 784 IBR procedures were identified, of which 584 were performed on patients with invasive breast cancer (implant-based, n = 288; autologous, n = 296). With a median follow-up of 71.3 months, the 10-year estimates of BCSS, DFS, and LRFS were 88.9% [95% confidence interval (CI) (85.1%-93.0%)], 79.6% [95% CI (74.7%-84.8%)], and 94.0% [95% CI (90.3%-97.8%)], respectively. A total of 124 patients completed the Breast-Q questionnaire, and no statistically significant differences were noted between groups (P = 0.823). After PSM with 27 variables, no statistically significant differences in BCSS, DFS, and LRFS were found between the implant-based (n = 177) and autologous (n = 177) groups. Further stratification according to staging, histological grade, lymph node status, and lymph-venous invasion status revealed no significant survival differences between groups. CONCLUSIONS: Both immediate implant-based and autologous reconstruction were reasonable choices with similar long-term oncological outcomes and patient-reported satisfaction among patients with invasive breast cancer in China.

Combined Effects of Mother's, Father's and Teacher's Psychological Distress on Schoolchildren's Mental Health Symptoms.

PURPOSE: Few studies have assessed the individual and joint effects of the mother's, father's and teacher's mental health symptoms on schoolchildren's behavior and emotional well-being simultaneously in the same study. PATIENTS AND METHODS: A cross-sectional survey was conducted among 8488 Chinese schoolchildren aged 6-17 years in northeast China. The Strengths and Difficulties Questionnaire (SDQ) and General Health Questionnaire (GHQ) were used to measure the mental health of the students, their parents and the teacher in charge of the class, respectively. A total of 6173 students (72.73%) with full mental health information from all three caretakers were included in the final analysis. RESULTS: We found a significantly elevated risk of mental health symptoms in children when their mothers (odds ratios (OR)=2.30, 95% CI=1.93-2.73), fathers (OR=2.08, 95% CI=1.73-2.50) and teachers (OR=1.18, 95% CI=1.01-1.39) reported poorer mental health, and the risk increased significantly with the number of the caretakers with mental symptoms. A father with poor mental health has both direct and indirect effects on a child's emotional health, by worsening the influence of a mother's poor mental health. CONCLUSION: All three caretakers have a significant negative influence on schoolchildren's emotional well-being, in the order of mother > father > teacher. It is desirable to assess and manage students' mental health in the both the family and school contexts.

RIPK1 is a negative mediator in Aquaporin 1-driven triple-negative breast carcinoma progression and metastasis.

The triple-negative breast carcinoma (TNBC) is the most aggressive subtype of breast cancer. In TNBC, Aquaporin 1 (AQP1), a water-transporting transmembrane protein, is aberrantly enriched in cytoplasm and causes tumor cell death evasion. However, the carcinogenetic bioactivities of cytoplasmic AQP1 cannot be attributed to the canonical "osmotic engine model". In the present study, the receptor-interacting protein kinase 1 (RIPK1), a cell death regulator, was identified to negatively mediate AQP1-driven TNBC progression and metastasis. AQP1 overabundance and RIPK1 depletion occurred in TNBC, which were correlated with aggressive oncological features and poor prognosis. AQP1 bound with RIPK1, resulting in the inhibition of RIPK1/RIPK3/MLKL-mediated necroptosis and RIPK1/caspase-8/caspase-3-mediated apoptosis. Genetic inhibition of RIPK1 significantly exacerbated the pro-tumor effect of AQP1, while ectopic expression of RIPK1 notably blunted AQP1 signaling. Mechanistically, AQP1 binds to the D324 site of RIPK1, and facilitates RIPK1 cleavage and inactivation by excessively activating the caspase-8/RIPK1 negative feedback loop. RIPK1D324K overexpression significantly prevented RIPK1 cleavage and weakened the aggressiveness of AQP1-enriched TNBC cells. Overall, our findings clarify the underlying mechanism of cytoplasmic AQP1-driven TNBC progression and metastasis, in which RIPK1 exerts an essential role as a negative mediator and exhibits the potential as a therapeutic target for TNBC.

LncRNA DANCR attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through regulating of miR-33a-5p/XBP1s.

Brain microvascular endothelial cell (BMEC) survival and angiogenesis after ischemic stroke has great significance for improving the prognosis of stroke. Abnormal variants of lncRNAs are closely associated with stroke. In this study, we examined the effects and molecular mechanisms of differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis, migration, and angiogenesis of oxygen-glucose deprivation (OGD)-treated BMECs. We found that DANCR expression significantly increased at 2, 4, 6, 8, and 10 h after OGD. DANCR overexpression promoted cell viability, migration, and angiogenesis in OGD-treated BMECs. Additionally, we found that X-box binding protein l splicing (XBP1s) expression was positively correlated with DANCR expression. DANCR overexpression promoted XBP1s expression in OGD-treated BMECs. Silenced XBP1s reversed the effect of DANCR in OGD-treated BMECs. Furthermore, we found that microRNA (miR)-33a-5p bound to DANCR and the 3'-UTR of XBP1. miR-33a-5p overexpression inhibited proliferation, migration, angiogenesis, and XBP1s expression in OGD-treated DANCR-overexpressing BMECs, reversing the protective effect of DANCR. Finally, we found that XBP1s expression promoted proliferation, migration, and angiogenesis, reversing the damaging effect of miR-33a-5p. In conclusion, DANCR enhanced survival and angiogenesis in OGD-treated BMECs through the miR-33a-5p/XBP1s axis.

Endogenous H2S-Activable Liposomal Nanoplatform for Synergistic Colorectal Tumor Ablation at Mild Apparent Temperature.

Photoinduced hyperthermia possesses great potential in photothermal therapy and thermal-responsive chemotherapy of tumors. However, traditional thermal-triggered drug release requires high temperature, which results in unpleasant activation of thermal-induced cellular self-protection. In this work, a Cu-complex modified and drug-loaded liposomal nanoplatform was constructed for endogenous H2S-activated synergistic ablation of colorectal tumors. In response to H2S, the incorporated Cu-complex contributed to the formation of semiconductor CuS on the surface of the as-designed liposomal nanoplatform, which led to local heating under near-infrared (NIR) laser irradiation to achieve simultaneous photothermal therapy and drug release. It is noteworthy that although the drug release occurred at a mild apparent temperature, it was actually triggered by the high eigen temperature on the surface of the liposomal nanoplatform. Therefore, efficient and synergistic photothermal and chemotherapy was achieved under mild apparent temperatures. This work provides insights into achieving selective and bioactivated photothermal therapy and therefore thermal-controlled drug release without using excessive hyperthermia.

Association of sociodemographic and oncological features with decision on implant-based versus autologous immediate postmastectomy breast reconstruction in Chinese patients.

BACKGROUND AND OBJECTIVES: Immediate postmastectomy breast reconstruction (IPBR) has gained wide popularity in China. We sought to clarify the prevalence and predictors of implant-based vs autologous IPBR among Chinese patients. METHODS: A retrospective cohort study was performed using a prospectively maintained database. Women who underwent IPBR during 2001-2017 were included. The modality-specific trends were deciphered by curve fitting analysis. The association of sociodemographic and oncological features with the decision for implant-based vs autologous IPBR was investigated using multivariate logistic regression and structural equation modeling. RESULTS: Among 905 patients included in the study, 479 underwent implant-based IPBR and 426 underwent autologous procedures. The implant/autologous ratio has increased exponentially over time. Multivariate analysis demonstrated that unmarried patients with BMI ≤ 24 kg/m2 , earlier clinical tumor stage, and preoperative pathological diagnosis of noninvasive lesion are more likely to choose implant-based IPBR compared to autologous procedures. The indirect effects of age, mastectomy type, and neoadjuvant chemotherapy were further demonstrated by the structural equations. CONCLUSIONS: The sociodemographic and oncological features are directly or indirectly associated with the decision on type of IPBR. The findings may facilitate both patients and physicians to make a high-quality decision by holistic evaluation of the sociodemographic and oncological features.

PCA-based GRS analysis enhances the effectiveness for genetic correlation detection.

Genetic risk score (GRS, also known as polygenic risk score) analysis is an increasingly popular method for exploring genetic architectures and relationships of complex diseases. However, complex diseases are usually measured by multiple correlated phenotypes. Analyzing each disease phenotype individually is likely to reduce statistical power due to multiple testing correction. In order to conquer the disadvantage, we proposed a principal component analysis (PCA)-based GRS analysis approach. Extensive simulation studies were conducted to compare the performance of PCA-based GRS analysis and traditional GRS analysis approach. Simulation results observed significantly improved performance of PCA-based GRS analysis compared to traditional GRS analysis under various scenarios. For the sake of verification, we also applied both PCA-based GRS analysis and traditional GRS analysis to a real Caucasian genome-wide association study (GWAS) data of bone geometry. Real data analysis results further confirmed the improved performance of PCA-based GRS analysis. Given that GWAS have flourished in the past decades, our approach may help researchers to explore the genetic architectures and relationships of complex diseases or traits.

Single-Surgeon Experience for Maximizing Outcomes in Implant-Based Breast Reconstruction in Chinese Patients.

INTRODUCTION: Breast reconstruction for Chinese patients is vastly different given cultural differences, patient preferences, access to resources, and insurance coverage in China. Given these unique factors, a different approach for optimizing outcomes should be considered. METHODS: Retrospective review of all patients undergoing implant-based breast reconstruction from January 2013 to May 2016 was performed. Esthetic evaluations were made both by the patients and 1 nonoperative surgeon at least 6 months postoperative, and patient satisfaction was assessed using the Breast-Q. RESULTS: Overall, 135 patients undergoing 141 implant-based breast reconstructions were reviewed. The majority of implants (n = 134) were placed in a subpectoral position, whereas 7 were placed prepectorally, and no acellular dermal matrix was used. Given the limitations in acellular dermal matrix usage, soft-tissue coverage was augmented with local regional flaps. Ninety-four reconstructions (66.7%) used latissimus dorsi, 39 (27.7%) used serratus anterior, and 7 (5.0%) used mastectomy skin flaps only for implant coverage. Four patients (2.8%) underwent revision surgery to the reconstructed breasts. Grade III and grade IV capsular contracture was observed in 10 (7.1%) and 2 (1.4%) reconstructions, respectively. Both the patient's and the surgeon's satisfaction were higher than 80% in breast symmetry. CONCLUSIONS: Our implant selection method fit the Chinese population characteristics and could be extended to different types of implant-based breast reconstruction. It produced good esthetic outcomes and was reproducible, predictable, and simple to master in the clinical setting.