Ultrasonic-driven degradation of organic pollutants using piezoelectric catalysts WS2/Bi2WO6 heterojunction composites.

Water pollution has been made worse by the widespread use of organic dyes and their discharge, which has coincided with the industry's rapid development. Piezoelectric catalysis, as an effective wastewater purification method with promising applications, can enhance the catalyst activity by collecting tiny vibrations in nature and is not limited by sunlight. In this work, we designed and synthesized intriguing WS2/Bi2WO6 heterojunction nanocomposites, investigated their shape, structure, and piezoelectric characteristics using a range of characterization techniques, and used ultrasound to accelerate the organic dye Rhodamine B (RhB) degradation in wastewater. In comparison to the pristine monomaterials, the results demonstrated that the heterojunction composites demonstrated excellent degradation and stability of RhB under ultrasonic circumstances. The existence of heterojunctions and the internal piezoelectric field created by ultrasonic driving work in concert to boost catalytic performance, and the organic dye's rate of degradation is further accelerated by the carriers that are mutually transferred between the composites.

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer: Unravelling challenges and future directions.

Colorectal cancer (CRC) is a complex disease with diverse etiologies and clinical outcomes. Despite considerable progress in development of CRC therapeutics, challenges remain regarding the diagnosis and management of advanced stage metastatic CRC (mCRC). In particular, the five-year survival rate is very low since mCRC is currently rarely curable. Over the past decade, cancer treatment has significantly improved with the introduction of cancer immunotherapies, specifically immune checkpoint inhibitors. Therapies aimed at blocking immune checkpoints such as PD-1, PD-L1, and CTLA-4 target inhibitory pathways of the immune system, and thereby enhance anti-tumor immunity. These therapies thus have shown promising results in many clinical trials alone or in combination. The efficacy and safety of immunotherapy, either alone or in combination with CRC, have been investigated in several clinical trials. Clinical trials, including KEYNOTE-164 and CheckMate 142, have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab, respectively, for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC. Unfortunately, these drugs benefit only a small percentage of patients, with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients. To this end, primary and secondary resistance to immunotherapy remains a significant issue, and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response. This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC. The underlying rationale, challenges faced, and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

DNA Hypomethylation-Mediated Transcription Dysregulation Participates in Pathogenesis of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a highly heterogeneous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidence suggests that abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in PCOS. Herein, a dehydroepiandrosterone-induced PCOS-like mouse model which has a similar metabolic and reproductive phenotype as human patients with PCOS was generated. It was used to experimentally validate the potential role of aberrant DNA methylation in PCOS in this study. Integrated DNA methylation and transcriptome analysis revealed the potential role of genomic DNA hypomethylation in transcription regulation of PCOS and identified several key candidate genes, including BMP4, Adcy7, Tnfaip3, and Fas, which were regulated by aberrant DNA hypomethylation. Moreover, i.p. injection of S-adenosylmethionine increased the overall DNA methylation level of PCOS-like mice and restored expression of the candidate genes to similar levels as the control, alleviating reproductive and metabolic abnormalities in PCOS-like mice. These findings provide direct evidence showing the importance of normal DNA methylation in epigenetic regulation of PCOS and potential targets for diagnosis and treatment of the disease.

Ecological transformation is the key to improve ecosystem health for resource-exhausted cities: A case study in China based on future development scenarios.

Numerous cities are currently grappling with the challenge of ecological transformation, especially those categorized as resource-exhausted cities. In these urban areas, land use change is a highly scrutinized issue, as different land use strategies can lead to varied outcomes, impacting the ecological environment in multiple dimensions. Assessing ecosystem health reflects the quality of the regional ecological environment and serves as a comprehensive indicator for evaluating the sustainability and stability of urban ecosystems. To this end, a multi-objective optimization model was constructed to predict land use changes under four future development scenarios (four ecological transformation modes), using Shizuishan City (China), a resource-exhausted city situated in an ecologically fragile area, as an example. The "vigor-organization-resilience" assessment framework was employed to evaluate the ecosystem health conditions in each scenario from three dimensions. The study results showed: (1) The ranking of the average ecological health levels in Shizuishan City for 2022 and different future development scenarios is as follows: Low-Carbon Economic Development Scenario (0.302) > Ecological-Economic Coordinated Development Scenario (0.291) > Baseline Scenario (0.290) > Economic Development Scenario (0.281) > 2022 (0.248). (2) Compared to 2022, the ecosystem health levels under the four ecological transformation modes had all improved, with improvement areas accounting for over 60 %, highlighting the urgent necessity of ecological transformation in Shizuishan City. Among them, the Low-Carbon Economic Development Scenario exhibited the largest improvement area, reaching 75.81 %. (3) Ecological system vitality was identified as the dominant dimension influencing the ecological health in this region. This study emphasized multi-objective development needs and provided an integrated ecosystem health assessment method for assessing the comprehensive ecological effects of future ecological transformation modes in resource-exhausted cities.

Prevalence of oral mucosal lesions in patients with systemic Lupus Erythematosus: a systematic review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause a range of symptoms, including oral mucosal lesions (OMLs). The prevalence of OMLs in SLE patients and their associated factors have been studied in various regions, but the results are inconsistent. This study aims to evaluate the prevalence of OMLs in patients with SLE. METHODS: Observational studies of OML prevalence in SLE patients published before 2022 were retrieved from PubMed, Embase, Web of Science, Google Scholar, and the Cochrane Library without language restriction. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ). RESULTS: Our meta-analysis included 113 studies with a total of 53,307 SLE patients. We found that the prevalence of OMLs in SLE patients was 31% (95% CI: 28%, 35%), with oral ulcers being present in 30% of SLE patients (95% CI: 26%, 33%). Subgroup analysis showed that the prevalence of OMLs varied significantly by region, disease activity, and sample size (p ≤ 0.01). However, gender and year of publication had little effect on the prevalence of OMLs (p = 0.78 and 0.30, respectively). Oral ulcers were significantly associated with age of onset (p = 0.02), geographic location (p < 0.01), and race (p < 0.01). We also found that the prevalence of oral erythema was 9%, oral candidiasis was 9%, petechiae was 8%, cheilitis was 6%, and white plaque was 3%. CONCLUSIONS: Our analysis showed that the prevalence of OMLs varied significantly by region and disease activity, and child-onset patients of Indian, Malay, and Caucasian descent were more likely to have oral ulcers. The high prevalence of OML in SLE patients emphasizes the importance of regular oral examination and management in the comprehensive care of individuals with SLE.

A T Cell-Engaging Tumor Organoid Platform for Pancreatic Cancer Immunotherapy.

Pancreatic ductal adenocarcinoma (PDA) is a clinically challenging disease with limited treatment options. Despite a small percentage of cases with defective mismatch DNA repair (dMMR), PDA is included in the most immune-resistant cancer types that are poorly responsive to immune checkpoint blockade (ICB) therapy. To facilitate drug discovery combating this immunosuppressive tumor type, a high-throughput drug screen platform is established with the newly developed T cell-incorporated pancreatic tumor organoid model. Tumor-specific T cells are included in the pancreatic tumor organoids by two-step cell packaging, fully recapitulating immune infiltration in the immunosuppressive tumor microenvironment (TME). The organoids are generated with key components in the original tumor, including epithelial, vascular endothelial, fibroblast and macrophage cells, and then packaged with T cells into their outside layer mimicking a physical barrier and enabling T cell infiltration and cytotoxicity studies. In the PDA organoid-based screen, epigenetic inhibitors ITF2357 and I-BET151 are identified, which in combination with anti-PD-1 based therapy show considerably greater anti-tumor effect. The combinatorial treatment turns the TME from immunosuppressive to immunoactive, up-regulates the MHC-I antigen processing and presentation, and enhances the effector T cell activity. The standardized PDA organoid model has shown great promise to accelerate drug discovery for the immunosuppressive cancer.

The unrelenting global expansion of the urban heat island over the last century.

The past century has seen dramatic increases in global temperatures and mounting urbanization. As a result of these events, the urban heat island (UHI) effect has received growing attention in scientific research worldwide. A global search was initially conducted using a scientific literature database to collect all available relevant publications to understand how the UHI has been expanding worldwide and affecting more cities across different latitudes and altitudes. Subsequently, a semantic analysis was performed to extract city names. The literature search and analysis combined resulted in 6078 publications in which UHI was investigated in 1726 cities worldwide in the 1901 to 2022 time period. The cities were grouped into 'first appearance' and 'recurrent appearance'. Results show that UHI was studied in only 134 cities during the 90-year period from 1901 to 1992, with a remarkable growth over time in the number of cities where interest in UHI increased. Interestingly, the number of first appearances was always notably higher than the number of recurrent appearances. The Shannon evenness index was employed to identify the spatial locations (hotspots) across the globe where UHI-related research has been concentrated in multiple cities over the last 120 years. Finally, Europe was selected as a testbed for conducting an analysis to shed light on how economic, demographic, and environmental factors can impact UHI. Our study is unique for having demonstrated not only the rapid growth of cities affected by UHI globally but also the increasing and unrelenting expansion of UHI occurrences across different latitudes and altitudes over time. These novel findings will undoubtedly be of interest to scientists investigating the UHI phenomenon and its trends. Stakeholders will acquire a broader perspective and deeper understanding of UHI in order to engage in more effective urban planning to offset and mitigate the phenomenon's adverse effects in the context of increasing climate change and urbanization.

Left Atrial and Ventricular Strain Differentiates Cardiac Amyloidosis and Hypertensive Heart Disease: A Cardiac MR Feature Tracking Study.

RATIONALE AND OBJECTIVES: Strain measured by feature tracking technique represents the degree of deformation and reflects the systolic and diastolic function of the heart. Our purpose was to evaluate the differential diagnostic value and correlations of left atrial (LA) strain (LAS) and left ventricular (LV) strain (LVS) in cardiac amyloidosis (CA) and hypertensive heart disease (HHD) patients. MATERIALS AND METHODS: We recruited 25 CA patients, 30 sex- and age-matched HHD patients and 20 healthy subjects totally. LAS and LVS were analyzed by CVI42 post-processing software. The efficiency of LAS and LVS in differentiating CA from HHD was compared by receiver operating characteristic curves analysis. Pearson or Spearman's analysis were used to assess the correlation between LAS and LV parameters. RESULTS: Both HHD and CA patients had impaired LVS, the gradient of increasing absolute values of longitudinal strain (LS) and radial strain (RS) from the basal to the apical myocardium was most pronounced in the CA group, its relative apical sparing of LS (RASLS) ratio reached 0.91 ± 0.02, significantly higher than other two groups (HHD: 0.72 ± 0.02; controls: 0.56 ± 0.01, all p <0.001). Additionally, except for the booster strain in the HHD group was preserved, all other LAS were reduced in patients' groups. The RASLS had the best differential diagnostic efficacy with an area under the curve (AUC) of 0.930 (p <0.001); The AUCs of LAS all greater than 0.850, above global LS (GLS) (AUC = 0.770, p = 0.001). LAS was notably correlated with LV ejection fraction (LVEF) and GLS, with reservoir strain having the greatest correlation with GLS (r = -0.828, p <0.001). CONCLUSION: The RASLS has high efficiency in guiding the differential diagnosis of CA and HHD with similar degree and presentation of LVH. Moreover, LAS values can also provide some useful information and they are closely linked with LV function, CMR feature tracking may provide assistance in the evaluation of LA-LV coupling.

3D whole-heart noncontrast coronary MR angiography based on compressed SENSE technology: a comparative study of conventional SENSE sequence and coronary computed tomography angiography.

OBJECTIVE: The relatively long scan time has hampered the clinical use of whole-heart noncontrast coronary magnetic resonance angiography (NCMRA). The compressed sensitivity encoding (SENSE) technique, also known as the CS technique, has been found to improve scan times. This study aimed to identify the optimal CS acceleration factor for NCMRA. METHODS: Thirty-six participants underwent four NCMRA sequences: three sequences using the CS technique with acceleration factors of 4, 5, and 6, and one sequence using the conventional SENSE technique with the acceleration factor of 2. Coronary computed tomography angiography (CCTA) was considered as a reference sequence. The acquisition times of the four NCMRA sequences were assessed. The correlation and agreement between the visible vessel lengths obtained via CCTA and NCMRA were also assessed. The image quality scores and contrast ratio (CR) of eight coronary artery segments from the four NCMRA sequences were quantitatively evaluated. RESULTS: The mean acquisition time of the conventional SENSE was 343 s, while that of CS4, CS5, and CS6 was 269, 215, and 190 s, respectively. The visible vessel length from the CS4 sequence showed good correlation and agreement with CCTA. The image quality score and CR from the CS4 sequence were not statistically significantly different from those in the other groups (p > 0.05). Moreover, the image score and CR showed a decreasing trend with the increase in the CS factor. CONCLUSIONS: The CS technique could significantly shorten the acquisition time of NCMRA. The CS sequence with an acceleration factor of 4 was generally acceptable for NCMRA in clinical settings to balance the image quality and acquisition time.

Dual-layer dual-energy CT for improving differential diagnosis of squamous cell carcinoma from adenocarcinoma at gastroesophageal junction.

Objective: To examine the clinical values of dual-energy CT parameters derived from dual-layer spectral detector CT (SDCT) in the differential diagnosis of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the gastroesophageal junction (GEJ). Methods: Totally 66 patients with SCC and AC of the GEJ confirmed by pathological analysis were retrospectively enrolled, and underwent dual-phase contrast-enhancement chest CT with SDCT. Plain CT value, CT attenuation enhancement (△CT), iodine concentration (IC), spectral slope (λHU), effective atomic number (Zeff) and 40keV CT value (CT40keV) of the lesion in the arterial phase (AP) and venous phase (VP) were assessed. Multivariate logistic regression analysis was performed to evaluate the diagnostic efficacies of different combinations of dual-energy CT parameters. Receiver operating characteristic (ROC) curves were used to analyze the accuracy of dual-energy CT parameters and Delong test was used to compare AUCs. Results: IC, λHU, Zeff and CT40keV in AP and VP and △CT in VP were significantly higher in the AC group than those in the SCC group (all P<0.05). ROC curve analysis showed that IC, λHU, Zeff and CT40keV in VP had high diagnostic performances, with AUCs of 0.74, 0.74, 0.79 and 0.78, respectively. Logistic regression showed the combination of ICVP, λHU VP, CT40keV VP and Zeff VP had the highest AUC (0.84), with a threshold of 0.40, sensitivity and specificity in distinguishing SCC and AC were 93.1% and 73.0%, respectively. Delong test showed that the AUC of △CTVP was lower than other AUCs of dual-energy CT parameters. Conclusion: Dual-energy CT parameters derived from SDCT provide added value in the differential diagnosis of SCC and AC of the GEJ, especially the combination of IC, λHU, CT40keV and Zeff in VP. Advances in knowledge: Dual-energy CT parameters derived from dual-layer spectral detector CT provide added value to differentiate AC from SCC at the GEJ, especially the combination of effective atomic number, spectral slope, iodine concentration and 40keV CT value in VP.

Thinning can increase shrub diversity and decrease herb diversity by regulating light and soil environments.

Tree thinning affects the light environment, which in turn affects the growth and survival of understory vegetation, thus improving species diversity and nutrient cycling, as well as the ecological habitat factors. However, the response of understory vegetation to the thinning intensity and short-time effects in the temperate broadleaf-conifer mixed forest is not completely clear. In this study, four permanent plots with a total area of 4 hm2 were established in a mixed broadleaf-conifer forest in northeast China, with thinning intensities of 20% (light thinning, LT), 35% (medium thinning, MT), 55% (heavy thinning, HT) and the unthinned plot (CK), respectively, in accordance with the basal area. The responses of species diversity to changes in understory vegetation were conducted by a structural equation model (SEM). The results showed that compared with CK, thinning significantly increased the photosynthetically active radiation (PAR) and the light quality (R/FR) (p < 0.05), while decreased the contents of soil total nitrogen (TN), total phosphorous (TP), organic matter (OM), nitrate nitrogen (NN), ammonia nitrogen (AN) and pH. The degree of fragmentation of light factors among the treatment plots gradually decreased as thinning intensity increased. Among all the thinning treatments, PAR and R/FR were found to be the optimal light condition when the forest thinning intensity was 55%. The light condition was found to have a significant negative correlation with soil TN, TP, OM, and AN. While the soil nutrients were positively correlated with herbaceous layer diversity but negatively correlated with shrub layer diversity. The soil nutrients were lost after thinning in a short time and herb diversity decreased, but shrub diversity increased significantly compared with unthinned plots. For the understory vegetation, the species diversity of shrub and herb layer were showed to be more sensitive to soil nutrients than light environment.

Manganese Dioxide-Based Nanocarrier Delivers Paclitaxel to Enhance Chemotherapy against Orthotopic Glioma through Hypoxia Relief.

Chemotherapy plays an important role in treating cancers in clinic. Hypoxia-mediated chemoresistance remains a major hurdle for effective tumor chemotherapy. Herein, a new class of tLyP-1-modified dopamine (DOPA)-ß-cyclodextrin (CD)-coated paclitaxel (PTX)- and manganese dioxide (MnO2 )-loaded nanoparticles (tLyP-1-CD-DOPA-MnO2 @PTX) is developed to enhance glioma chemotherapy. The nanomedicine delivered to the tumor site decomposes in response to the weak acidity and high hydrogen peroxide in the tumor microenvironment (TME), resulting in collapse of the system to release PTX and generates Mn2+ and O2 . In a rat model of intracranial glioma, tLyP-1-CD-DOPA-MnO2 @PTX can efficiently pass through the blood-brain-barrier to accumulate in tumor sites. The hypoxia in TME can be relieved via O2 generated by MnO2 and the reactive oxygen species produced by Mn2+ can kill tumor cells. The tLyP-1-CD-DOPA-MnO2 @PTX nanoparticles exert a remarkable antitumor effect by promoting apoptosis and inhibiting proliferation of tumor cells in addition to enabling real-time tumor monitoring with magnetic resonance imaging. This MnO2 -based theranostic medicine will offer a novel strategy to simultaneously enhance chemotherapy and achieve real-time imaging of therapeutic process in glioma treatment.

Leaf functional traits differentiation in relation to covering materials of urban tree pits.

BACKGROUND: Understanding the ecological strategies of urban trees to the urban environment is crucial to the selection and management of urban trees. However, it is still unclear whether urban tree pit cover will affect plant functional traits. Here, we study the response of urban trees to different tree pit covers, analyzed the effects of different cover types on soil properties and their trade-off strategies based on leaf functional traits. RESULTS: We found that there were obvious differences in the physical properties of the soil in different tree pit covers. Under the different tree pit cover types, soil bulk density and soil porosity reached the maximum under cement cover and turf cover, respectively. We found that tree pit cover significantly affected the leaf properties of urban trees. Leaf thickness, chlorophyll content index and stomatal density were mainly affected by soil bulk density and non-capillary porosity in a positive direction, and were affected by soil total porosity and capillary porosity in a negative direction. Leaf dry matter content and stomata area were mainly negatively affected by soil bulk density and non-capillary porosity, and positively affected by soil total porosity and capillary porosity. Covering materials of tree pits promoted the functional adjustment of plants and form the best combination of functions. CONCLUSION: Under the influence of tree pit cover, plant have low specific leaf area, stomata density, high leaf thickness, chlorophyll content index, leaf dry matter content, leaf tissue density and stomata area, which belong to "quick investment-return" type in the leaf economics spectrum.

Leaf reflectance and functional traits as environmental indicators of urban dust deposition.

BACKGROUND: How to quickly predict and evaluate urban dust deposition is the key to the control of urban atmospheric environment. Here, we focus on changes of plant reflectance and plant functional traits due to dust deposition, and develop a prediction model of dust deposition based on these traits. RESULTS: The results showed that (1) The average dust deposition per unit area of Ligustrum quihoui leaves was significantly different among urban environments (street (18.1001 g/m2), community (14.5597 g/m2) and park (9.7661 g/m2)). Among different urban environments, leaf reflectance curves tends to be consistent, but there were significant differences in leaf reflectance values (park (0.052-0.585) > community (0.028-0.477) > street (0.025-0.203)). (2) There were five major reflection peaks and five major absorption valleys. (3) The spectral reflectances before and after dust removal were significantly different (clean leaves > dust-stagnant leaves). 695 ~ 1400 nm was the sensitive range of spectral response. (4) Dust deposition has significant influence on slope and position of red edge. Red edge slope was park > community > street. After dust deposition, the red edge position has obviously "blue shift". The moving distance of the red edge position increases with the increase of dust deposition. The forecast model of dust deposition amount established by simple ratio index (y = 2.517x + 0.381, R2 = 0.787, RMSE (root-mean-square error) = 0.187. In the model, y refers to dust retention, x refers to simple ratio index.) has an average accuracy of 99.98%. (5) With the increase of dust deposition, the specific leaf area and chlorophyll content index decreased gradually. The leaf dry matter content, leaf tissue density and leaf thickness increased gradually. CONCLUSION: In the dust-polluted environment, L. quihoui generally presents a combination of characters with lower specific leaf area, chlorophyll content index, and higher leaf dry matter content, leaf tissue density and leaf thickness. Leaf reflectance spectroscopy and functional traits have been proved to be effective in evaluating the changes of urban dust deposition.

An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity.

In breast cancer, genetic heterogeneity, the lack of actionable targets and immune evasion all contribute to the limited clinical response rates to immune checkpoint blockade therapy. Here, we report a high-throughput screen based on the functional interaction of mouse- or patient-derived breast tumour organoids and tumour-specific cytotoxic T cells for the identification of epigenetic inhibitors that promote antigen presentation and potentiate T-cell-mediated cytotoxicity. We show that the epigenetic inhibitors GSK-LSD1, CUDC-101 and BML-210, identified by the screen, display antitumour activities in orthotopic mammary tumours in mice, that they upregulate antigen presentation mediated by the major histocompatibility complex class I on breast tumour cells and that treatment with BML-210 substantially sensitized breast tumours to the inhibitor of the checkpoint programmed death-1. Standardized measurements of tumour-cell killing activity facilitated by tumour-organoid-T-cell screens may help with the identification of candidate immunotherapeutics for a range of cancers.

Profiling Long Non-coding RNA expression Using Custom-Designed Microarray.

Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. The abnormal expression of lncRNAs has been implicated in a range of many human diseases, including cancer. To date, a small number of functional lncRNAs have been well characterized. lncRNA expression profiling may help to identify useful molecular biomarkers and targets for novel therapeutic approaches. In this chapter, we describe a highly efficient lncRNA expression profiling method using a custom-designed microarray.