Remittance from migrants reinforces forest recovery for China's reforestation policy.

Forests play a key role in the mitigation of global warming and provide many other vital ecosystem goods and services. However, as forest continues to vanish at an alarming rate from the surface of the planet, the world desperately needs knowledge on what contributes to forest preservation and restoration. Migration, a hallmark of globalization, is widely recognized as a main driver of forest recovery and poverty alleviation. Here, we show that remittance from migrants reinforces forest recovery that would otherwise be unlikely with mere migration, realizing the additionality of payments for ecosystem services for China's largest reforestation policy, the Conversion of Cropland to Forest Program (CCFP). Guided by the framework that integrates telecoupling and coupled natural and human systems, we investigate forest-livelihood dynamics under the CCFP through the lens of rural out-migration and remittance using both satellite remote sensing imagery and household survey data in two representative sites of rural China. Results show that payments from the CCFP significantly increases the probability of sending remittance by out-migrants to their origin households. We observe substantial forest regeneration and greening surrounding households receiving remittance but forest decline and browning in proximity to households with migrants but not receiving remittance, as measured by forest coverage and the Enhanced Vegetation Index derived from space-borne remotely sensed data. The primary mechanism is that remittance reduces the reliance of households on natural capital from forests, particularly fuelwood, allowing forests near the households to recover. The shares of the estimated ecological and economic additionality induced by remittance are 2.0% (1.4%∼3.8%) and 9.7% (5.0%∼15.2%), respectively, to the baseline of the reforested areas enrolled in CCFP and the payments received by the participating households. Remittance-facilitated forest regeneration amounts to 12.7% (6.0%∼18.0%) of the total new forest gained during the 2003-2013 in China. Our results demonstrate that remittance constitutes a telecoupling mechanism between rural areas and cities over long distances, influencing the local social-ecological gains that the forest policy intended to stimulate. Thus, supporting remittance-sending migrants in cities can be an effective global warming mitigation strategy.

KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Osteogenic effect of low-intensity pulsed ultrasound on peri-implant bone: A systematic review and meta-analysis.

Purpose This study aimed to evaluate the effect of low-intensity pulsed ultrasound (LIPUS) on promoting osseointegration around dental implants.Study selection A comprehensive search was performed on two databases, including MEDLINE (PubMed) and Web of Science to identify relevant studies published before June 1, 2022. Randomized controlled trials that met the inclusion criteria were selected for the study. The year of publication, study design, animal species, number of animals, number of implants, implant position, implant size, intervention, follow-up time, bone volume ratio (BV/TV), bone-implant contact ratio (BIC), and implant removal torque value (RTV) measurements, including mean and SD, were extracted.Results Ten randomized trials were included in this meta-analysis. The results showed that LIPUS significantly promoted osteogenesis around dental implants. Furthermore, in animal models of pre-existing diseases such as osteoporosis and diabetes, LIPUS had the same effect. The included data were divided into subgroups to explore the effects of different follow-up time, acoustic intensities, and frequencies. Results showed that higher acoustic intensities and frequencies significantly improve the osteogenic effects of LIPUS. There was some degree of heterogeneity owing to bias in the included studies. More high-quality randomized controlled trials are necessary in the future.Conclusions LIPUS can promote bone healing around dental implants and is an attractive option for edentulous patients, especially those with pre-existing diseases. Further clinical trials on the use of LIPUS in implant dentistry are warranted. Furthermore, future studies must pay more attention to acoustic intensity and frequency.

Prediction of percutaneous nephrolithotomy outcomes and flexible ureteroscopy outcomes using nephrolithometry scoring systems.

BACKGROUND: Kidney stones account for a high proportion of urological emergencies. The main objective of this paper is to evaluate the predictive ability of five scoring systems for overall stone-free status and postoperative complications after percutaneous nephrolithotomy and retrograde ureteroscopy. MATERIALS AND METHODS: This study retrospectively analysed 312 cases of kidney stone patients between January 2021 and May 2022 at our centre. Multivariate logistic regression as well as ROC curves were applied to determine the ability to evaluate each scale to predict stone-free rates and postoperative complications. RESULTS: 179 patients have undergone PCNL. After multivariate logistic regression, the S.T.O.N.E score and history of ipsilateral renal surgery were predictive of stone-free status, and the predictive power of the S.T.O.N.E score was higher than that of history of ipsilateral renal surgery. Grade 1 complications were considered to be related to Guy's score and grade 2 complications were considered to be related to history of diabetes mellitus. 133 patients have undergone f-URS. After multivariate logistic regression analysis, the modified S-ReSC score, RUSS score, and R.I.R.S score were predictive of stone-free status, with the R.I.R.S score being the strongest predictor. Evidence of grade 2 complications was considered to be related to abnormal renal function. CONCLUSION: For PCNL, the S.T.O.N.E score had the best efficacy in predicting stone-free status, and the Guy's score had the best efficacy in predicting postoperative complications; for f-URS, the R.I.R.S score had the best efficacy in predicting stone-free status, and no scoring system predicted postoperative complications.

The safety and efficacy of emergency stenting during bridging therapy: A Single-Center Retrospective Study.

INTRODUCTION: To investigated the safety and efficacy of emergency stenting for patients with ischemic stroke treated with bridging therapy. METHODS: Patients with onset of stroke who underwent bridging therapy were included in the two groups with emergency stenting (ESG) and without stenting (NSG). To avoid the bias due to confounding variables, subjects were further assigned in two groups using 1:1 propensity score matching (PSM). The safety outcomes include the incidence of intracranial hemorrhage (ICH), parenchymal hemorrhage type 2 (PH2), symptomatic intracranial hemorrhage (sICH), fatal hemorrhage, and mortality. The efficacy outcomes include successful recanalization, three-month favorable outcome (modified Rankin Scale [mRS]: 0-2). RESULTS: 175 patients treated with bridging therapy were included in this study, with 52 patients in the ES group and 123 patients in the groups without ES, and with 30 patients in each group after PSM. No significant differences in the incidences of ICH, PH2, sICH, fatal hemorrhage, and mortality were found between the two groups with ES and without ES before and after PSM (P>0.05 for all groups). The analysis without PSM showed that the group with ES had a higher rate of successful recanalization (98.1% vs. 81.6%，P=0.041) than the group without ES, but no significant difference was seen (96.6% vs. 93.3%，P=0.554) between the two groups after PSM. There was no difference in favorable outcome between the two groups before and after matching as well (P>0.05). CONCLUSIONS: It is safe and effective for patients with onset of ischemic stroke to receive emergency stenting during bridging therapy, without increasing the risk of hemorrhagic transformation and mortality.

Ae index is an independent predictor of kidney stone recurrence in overweight and obese patients.

BACKGROUND: Finding some convenient and economical indicators to initially screen overweight and obese patients at high risk of kidney stone recurrence can help them prevent stone recurrence with lower medical cost. The purpose of this article is to determine the clinical value of Ae index (Apo B × 1000/eGFR) as an independent predictor for kidney stone recurrence in overweight and obese populations. METHODS: We queried the electronic medical records of patients with kidney stone operated at our hospital from March 2016 to March 2022, and selected BMI ≥ 25 kg/m2 as the study population and divided the patients into stone recurrence group and non-recurrence group. Relevant parameters of routine blood and biochemical test, glycated serum protein (GSP), and history of hypertension and hyperglycemia were collected. Then the Chi-square test, independent samples t-test or Wilcoxon rank-sum test were used to calculate the differences between the two groups of data. Next, we performed univariate and multivariate logistic regression analysis to screen out the most significant variables Apo B and eGFR, and then we calculated the Ae index using the formula Apo B × 1000/eGFR, and analyzed the relationship between Ae index and kidney stone recurrence. RESULTS: Univariate analysis found that Apo B (OR:8.376,95%CI:3.093-22.680), Creatinine (OR:1.012,95%CI:1.003-1.021), Cystatin C(OR:2.747,95%CI:1.369-5.508), LDL-C (OR:1.588,95%CI:1.182-2.134), TC (OR:1.543,95%CI:1.198-1.988) were positively associated, eGFR (OR:0.980,95%CI:0.970-0.991) was negatively associated with kidney stone recurrence. And multivariate logistic regression analysis suggested that Apo B (OR:11.028, 95%CI:3.917-31.047) and eGFR (OR:0.976, 95%CI:0.965-0.988) were the most significant factors. Then we calculated Ae index and analyzed it, the sensitivity was 74.26% and the specificity was 60.00%, higher than either individual variable. Its smoothed curve revealed a non-linear relationship between them with the inflection point of 9.16. And the OR on the left side of the inflection point was 1.574 (95% CI: 1.228-2.018), whereas the OR on the right side of the inflection point was 1.088 (95% CI: 1.007-1.177). CONCLUSIONS: Ae index is an easily calculated and obtained index that has some predictive value for kidney stone recurrence in overweight and obese patients, which is of interest.

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.

Establishment of a new predictive model for the recurrence of upper urinary tract stones.

PURPOSE: To construct a nomogram for evaluation of the recurrence risk of upper urinary tract stones in patients. METHODS: We retrospectively reviewed the clinical data of 657 patients with upper urinary tract stones and divided them into stone recurrence group and non-recurrence group. Blood routine, urine routine, biochemical, and urological CT examinations were searched from the electronic medical record, relevant clinical data were collected, including age, BMI, stones number and location, maximum diameter, hyperglycemia, hypertension, and relevant blood and urine parameters. The Wilcoxon rank-sum test, independent sample t test, and Chi-square test were used to preliminarily analyze the data of the two groups, then LASSO and logistic regression analysis were used to find out the significant difference indicators. Finally, R software was used to draw a nomogram to construct the model, and ROC curve was drawn to evaluate the sensitivity and specificity. RESULTS: The results showed that multiple stones (OR: 1.832, 95% CI 1.240-2.706), bilateral stones (OR: 1.779, 95% CI 1.226-2.582), kidney stones (OR: 3.268, 95% CI 1.638-6.518), and kidney ureteral stones (OR: 3.375, 95% CI 1.649-6.906) were high risk factors. And the stone recurrence risk was positively correlated with creatinine (OR: 1.012, 95% CI 1.006-1.018), urine pH (OR: 1.967, 95% CI 1.343-2.883), Apo B (OR: 4.189, 95% CI 1.985-8.841) and negatively correlated with serum phosphorus (OR: 0.282, 95% CI 0.109-0.728). In addition, the sensitivity and specificity of the prediction model were 73.08% and 61.25%, diagnosis values were greater than any single variable. CONCLUSION: The nomogram model can effectively evaluate the recurrence risk of upper urinary stones, especially suitable for stone postoperative patients, to help reduce the possibility of postoperative stone recurrence.

Understanding the mediating role of labor out-migration in household income generation and distribution under a reforestation policy in rural China.

Income inequality is a critical issue of socio-economic development, particularly in rural areas where forest-dependent people are often vulnerable to the intervention of forest policies. This paper aims to elucidate income distribution and inequality of rural households influenced by China's largest reforestation policy implemented in early 2000s. Drawing on socioeconomic and demographic data from household surveys in two rural sites, we applied the Gini coefficient to measure income inequality and used a regression-based approach to examine the underlying factors that are associated with income generation among households. We also performed a mediation analysis to test the role of labor out-migration in shaping household income distribution under the reforestation policy. Results show that remittances sent by rural out-migrants substantially contribute to household income but tend to worsen inequality, particularly for households having retired cropland for reforestation. The inequality in total income depends on capital accumulation for land endowment and labor availability that render diversified livelihoods possible. Such linkage reveals regional disparity, which, along with policy-implementing institutions (e.g., rules for tree species choice for reforestation), can influence income generation from a given source (e.g., agriculture). Rural out-migration of female labor significantly mediates the economic benefits of the policy delivered to the households with an estimated mediating share of 11.7%. These findings add value to the knowledge of poverty-environment interrelationships in a sense that supporting rural livelihoods of the more vulnerable and underrepresented groups is essential for securing and sustaining the stewardship of forests. Policymaking for such forest restoration programs needs to integrate strategies for targeted or precise poverty alleviation to strengthen the conservation effectiveness.

Spatial analysis of stromal signatures identifies invasive front carcinoma-associated fibroblasts as suppressors of anti-tumor immune response in esophageal cancer.

BACKGROUND: Increasing evidence indicates that the tumor microenvironment (TME) is a crucial determinant of cancer progression. However, the clinical and pathobiological significance of stromal signatures in the TME, as a complex dynamic entity, is still unclear in esophageal squamous cell carcinoma (ESCC). METHODS: Herein, we used single-cell transcriptome sequencing data, imaging mass cytometry (IMC) and multiplex immunofluorescence staining to characterize the stromal signatures in ESCC and evaluate their prognostic values in this aggressive disease. An automated quantitative pathology imaging system determined the locations of the lamina propria, stroma, and invasive front. Subsequently, IMC spatial analyses further uncovered spatial interaction and distribution. Additionally, bioinformatics analysis was performed to explore the TME remodeling mechanism in ESCC. To define a new molecular prognostic model, we calculated the risk score of each patient based on their TME signatures and pTNM stages. RESULTS: We demonstrate that the presence of fibroblasts at the tumor invasive front was associated with the invasive depth and poor prognosis. Furthermore, the amount of α-smooth muscle actin (α-SMA)+ fibroblasts at the tumor invasive front positively correlated with the number of macrophages (MØs), but negatively correlated with that of tumor-infiltrating granzyme B+ immune cells, and CD4+ and CD8+ T cells. Spatial analyses uncovered a significant spatial interaction between α-SMA+ fibroblasts and CD163+ MØs in the TME, which resulted in spatially exclusive interactions to anti-tumor immune cells. We further validated the laminin and collagen signaling network contributions to TME remodeling. Moreover, compared with pTNM staging, a molecular prognostic model, based on expression of α-SMA+ fibroblasts at the invasive front, and CD163+ MØs, showed higher accuracy in predicting survival or recurrence in ESCC patients. Regression analysis confirmed this model is an independent predictor for survival, which also identifies a high-risk group of ESCC patients that can benefit from adjuvant therapy. CONCLUSIONS: Our newly defined biomarker signature may serve as a complement for current clinical risk stratification approaches and provide potential therapeutic targets for reversing the fibroblast-mediated immunosuppressive microenvironment.

Multifunctionalized carbon-fiber-reinforced polyetheretherketone implant for rapid osseointegration under infected environment.

Carbon fiber reinforced polyetheretherketone (CFRPEEK) possesses a similar elastic modulus to that of human cortical bone and is considered as a promising candidate to replace metallic implants. However, the bioinertness and deficiency of antibacterial activities impede its application in orthopedic and dentistry. In this work, titanium plasma immersion ion implantation (Ti-PIII) is applied to modify CFRPEEK, achieving unique multi-hierarchical nanostructures and active sites on the surface. Then, hybrid polydopamine (PDA)@ZnO-EDN1 nanoparticles (NPs) are introduced to construct versatile surfaces with improved osteogenic and angiogenic properties and excellent antibacterial properties. Our study established that the modified CFRPEEK presented favorable stability and cytocompatibility. Compared with bare CFRPEEK, improved osteogenic differentiation of rat mesenchymal stem cells (BMSCs) and vascularization of human umbilical vein endothelial cells (HUVECs) are found on the functionalized surface due to the zinc ions and EDN1 releasing. In vitro bacteriostasis assay confirms that hybrid PDA@ZnO NPs on the functionalized surface provided an effective antibacterial effect. Moreover, the rat infected model corroborates the enhanced antibiosis and osteointegration of the functionalized CFRPEEK. Our findings indicate that the multilevel nanostructured PDA@ZnO-EDN1 coated CFRPEEK with enhanced antibacterial, angiogenic, and osteogenic capacity has great potential as an orthopedic/dental implant material for clinical application.

Identification of hub biomarkers and immune cell infiltration characteristics of polymyositis by bioinformatics analysis.

Background: Polymyositis (PM) is an acquirable muscle disease with proximal muscle involvement of the extremities as the main manifestation; it is a category of idiopathic inflammatory myopathy. This study aimed to identify the key biomarkers of PM, while elucidating PM-associated immune cell infiltration and immune-related pathways. Methods: The gene microarray data related to PM were downloaded from the Gene Expression Omnibus database. The analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks were performed on differentially expressed genes (DEGs). The hub genes of PM were identified using weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) algorithm, and the diagnostic accuracy of hub markers for PM was assessed using the receiver operating characteristic curve. In addition, the level of infiltration of 28 immune cells in PM and their interrelationship with hub genes were analyzed using single-sample GSEA. Results: A total of 420 DEGs were identified. The biological functions and signaling pathways closely associated with PM were inflammatory and immune processes. A series of four expression modules were obtained by WGCNA analysis, with the turquoise module having the highest correlation with PM; 196 crossover genes were obtained by combining DEGs. Subsequently, six hub genes were finally identified as the potential biomarkers of PM using LASSO algorithm and validation set verification analysis. In the immune cell infiltration analysis, the infiltration of T lymphocytes and subpopulations, dendritic cells, macrophages, and natural killer cells was more significant in the PM. Conclusion: We identified the hub genes closely related to PM using WGCNA combined with LASSO algorithm, which helped clarify the molecular mechanism of PM development and might have great significance for finding new immunotherapeutic targets, and disease prevention and treatment.

Association between body fat distribution and kidney stones: Evidence from a US population.

Objectives: We aimed to evaluate the relationship between the proportion of Android to Gynoid ratio and the incidence of kidney stones among US adults. Methods: Participants aged 20-59 years from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) database were selected to assess the association between Android to Gynoid ratio and kidney stone prevalence using logistic regression analysis, subgroup analysis and calculation of dose-response curves. Results: This study ultimately included 10858 participants, of whom 859 self-reported a history of kidney stones. And after adjusting for all confounders, an increased Android to Gynoid ratio was associated with an increased prevalence of kidney stones (OR=2.75, 95% CI:1.62-4.88). And subgroup analysis showed an increased prevalence of kidney stones in women (OR=3.55, 95% CI: 1.54-8.22), non-diabetic (OR=2.59, 95% CI: 1.45-4.60), 60 > age ≥ 40 years (OR=3.51, 95% CI: 1.83-6.71), Mexican-American (OR=4.35, 95% CI: 1.40- 13.53) and white (OR=3.86, 95% CI: 1.82-8.18) groups, there was a significant positive association between A/G ratio and kidney stones. In contrast, in the hypertensive subgroup, the A/G ratio was associated with kidney stones in all groups. Conclusions: Higher Android to Gynoid ratio is associated with a high prevalence of kidney stone disease.

Pyroptosis-related gene-based prognostic signature for predicting the overall survival of oral squamous cell carcinoma patients.

Purpose: Oral squamous cell carcinoma (OSCC) is the most common oral cancer worldwide. Pyroptosis is a type of programmed cell death mediated by caspase, accompanied by an inflammatory response, and plays an important role in cancer progression. The purpose of this study was to explore and identify potential biomarkers and further elucidate the potential role of cell pyroptosis in OSCC. Methods: We regarded the samples from The Cancer Genome Atlas database as a training dataset, screened differentially expressed genes (DEGs), and further screened out OSCC phenotypic characteristic genes by using weighted gene co-expression network analysis. The analysis of 42 known pyroptosis-related genes showed that Psuch genes were widely expressed, mutated, and methylated in OSCC samples. Results: Through correlation analysis, we identified our OSCC pyroptosis-related DEGs. To further evaluate the prognostic value of pyroptosis-related regulators, we constructed a seven gene-based prognostic signature using Cox univariate analysis and least absolute shrinkage and selection operator Cox regression analysis. Meanwhile, we found that patients in the low-risk group had higher immune infiltration. Moreover, our results also indicated significant differences in sensitivity to cisplatin and gefitinib between the high-risk and low-risk groups. Conclusion: Our study successfully constructed the pyroptosis-related prognostic signature, which might play a potential prediction role in OSCC prognosis. Our findings also suggested that pyroptosis-related regulators might be novel biomarkers for tumor diagnosis and treatment in OSCC.

Mutational landscape of pan-cancer patients with PIK3CA alterations in Chinese population.

PURPOSE: To analyze the mutational landscape of pan-cancer patients with PIK3CA mutations in Chinese population in real-world. METHODS: We analyzed PIK3CA mutation status in sequencing data of cell-free DNA from plasma and genomic DNA from matched peripheral blood lymphocyte in 11,904 Chinese pan-cancer patients, and compared them with genomic data from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Besides, concomitant genomic aberrations in PIK3CA-mutated samples were detected to investigate cancer driver genes, as well as their enriched pathways. Meanwhile, the mutations of Alpelisib targeting genes were screened and their co-alterations were analyzed according to OncoKB definition to identify the potential actionable ones. RESULTS: The proportion of patients with PIK3CA mutations varied among 21 types of cancer, with the top being BRCA, CESC, SCL, and UCEC. The most common PIK3CA mutation hotspots were found to be E545K, E542K and H1047R. The Chinese cohort had significantly lower frequencies of PIK3CA mutations in breast and stomach cancers, but markedly higher PIK3CA mutation frequencies in large intestine, kidney and lung cancers than the COSMIC cohort. Compared with COSMIC cohort, the mutation frequencies of Alpelisib-targeted genes in breast cancer were significantly reduced in the Chinese cohort. All PIK3CA-mutated patients had concomitant genomic aberrations. While the most common concomitant genomic alterations occurred in TP53, EGFR and FAT1, these co-mutated genes were mainly enriched in RTK/RAS pathway, PI3K pathway and P53 pathway. Moreover, 83.6% of patients carrying mutations in Alpelisib-targeted genes had at least one actionable concomitant alteration. Level 1 actionable alteration was identified in LUAD, BRCA, COAD, LUSC, READ, and STAD. CONCLUSION: Compared with the Western cohort, the mutation frequency of PIK3CA in breast cancer was reduced in the Chinese cohort. RTK/RAS pathway, PI3K pathway and P53 pathway were identified as the most common co-mutation pathways, suggesting that they may potentially serve as targets for possible Alpelisib-based combination therapy.

Microfluidics-Based Time-Resolved Fluorescence Immunoassay for the On-Site Detection of Aflatoxins B1 Zearalenone and Deoxynivalenol in Cereals.

The primary pollutants in cereal products are aflatoxins B1 (AFB1), zearalenone (ZEN), and deoxynivalenol (DON). In this study, anti-AFB1 MAb (4C9), anti-ZEN MAb (2A3), and anti-DON MAb (1F10) were developed and used in time-resolved fluorescence immunoassay microfluidics to determine AFB1, ZEN, and DON in agricultural products. The linear range for AFB1, ZEN, and DON were 0.05~2.2 µg/kg, 1.45~375.75 µg/kg, and 11.1~124.2 µg/kg, respectively. In maize, the recoveries of AFB1/ZEN/DON were 92~101%, 102~105%, and 103~108%, respectively. High-performance liquid chromatography and the proposed approach had a good correlation. Time-resolved fluorescence immunoassay microfluidics is a highly efficient and sensitive field detection method for fungal toxins in agricultural products.

Circular RNA Sirtuin1 represses pulmonary artery smooth muscle cell proliferation, migration and autophagy to ameliorate pulmonary hypertension via targeting microRNA-145-5p/protein kinase-B3 axis.

Recently, several studies have been clarified that circular RNA (circRNA) was a vital regulatory gene of pulmonary hypertension (PH). Nevertheless, the action of circRNA in PH was not yet explored. This study was to figure out the biological function and potential molecular mechanism of circSirtuin1 (SIRT1) in PH. Construction of the PH rat model and hypoxia pulmonary artery smooth muscle cells (PASMC) model was performed, and test of circSIRT1/microRNA (miR)-145-5p/protein kinase-B3 (Akt3) was conducted. The influence of the circSIRT1/miR-145-5p/Akt3 axis on the histopathology, hemodynamics with autophagy of the pulmonary artery in rats was examined. Additionally, the impact of circSIRT1/miR-145-5p/Akt3 on the proliferation, migration and apoptosis with autophagy of PASMC under hypoxic environment was also determined. The targeting of circSIRT1/miR-145-5p/Akt3 was testified. The results manifested that circSIRT1 and Akt3 were elevated in PH, while miR-145-5p was declined. Knockdown of circSIRT1 ameliorated rat PH, suppressed PASMC proliferation, migration with autophagy in hypoxic environment. CircSIRT1 competitively combined with miR-145-5p to mediate Akt3. To sum up, circSIRT1/miR-145-5p/Akt3 was supposed to perform as a prospective molecular target for the treatment of PH.

Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment.

The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

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.

STAT3ß disrupted mitochondrial electron transport chain enhances chemosensitivity by inducing pyroptosis in esophageal squamous cell carcinoma.

The clinical efficacy of cisplatin in the treatment of esophageal squamous cell carcinoma (ESCC) is undesirable. Signal transducer and activator of transcription 3ß (STAT3ß), a splice variant of STAT3, restrains STAT3α activity and enhances chemosensitivity in ESCC. However, the underlying molecular mechanisms remain poorly understood. Here, we found that high expression of STAT3ß contributes to cisplatin sensitivity and enhances Gasdermin E (GSDME) dependent pyroptosis in ESCC cells after exposure to cisplatin. Mechanistically, STAT3ß was located into the mitochondria and its high expression disrupts the activity of the electron transport chain, resulting in an increase of ROS in cisplatin treatment cells. While high levels of ROS caused activation of caspase-3 and GSDME, and induced cell pyroptosis. STAT3ß blocked the phosphorylation of STAT3α S727 in mitochondria by interacting with ERK1/2 following cisplatin treatment, disrupting electron transport chain and inducing activation of GSDME. Clinically, high expression of both STAT3ß and GSDME was strongly associated with better overall survival and disease-free survival of ESCC patients. Overall, our study reveals that STAT3ß sensitizes ESCC cells to cisplatin by disrupting mitochondrial electron transport chain and enhancing pyroptosis, which demonstrates the prognostic significance of STAT3ß in ESCC therapy.