Synthesis, magnetic properties, biotoxicity and potential mechanism of modified nano zero-valent iron for decolorization of dye wastewater.

SiO2-coated nano zero-valent iron (nZVI) has emerged as a fine material for the treatment of dye wastewater due to its large specific surface area, high surface activity, and strong reducibility. However, the magnetic properties based on which SiO2-coated nZVI (SiO2-nZVI) could effectively separate and recover from treated wastewater, and the biotoxicity analysis of degradation products of the dye wastewater treated by SiO2-nZVI remain unclear. In this study, SiO2-nZVI was synthesized using a modified one-step synthesis method. The SiO2-nZVI nanoparticles were characterized using Transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, Fully automatic specific surface and porosity analyzer, Vibrating sample magnetometer, and Zeta potential analyzer. The removal rate of methyl orange (MO) by SiO2-nZVI composite reached 98.35% when the degradation performance of SiO2-nZVI treating MO was optimized. Since SiO2-nZVI analysed by magnetic hysteresis loops had large saturation magnetization and strong magnetic properties, SiO2-nZVI exhibited excellent ferromagnetic behaviour. The analysis of the degradation products showed that the MO treated by SiO2-nZVI was converted into a series of intermediates, resulting in reducing the toxicity of MO. The potential mechanism of MO degradated by SiO2-nZVI was speculated through degradation process and degradation kinetics analysis. Overall, the SiO2-nZVI composite may be regarded as a promising catalyst for decolorization of dye wastewater.

Synergistic Regulation of Targeted Organelles in Tumor Cells to Promote Photothermal-Immunotherapy Using Intelligent Core-Satellite-Like Nanoparticles for Effective Treatment of Breast Cancer.

The normal operation of organelles is critical for tumor growth and metastasis. Herein, an intelligent nanoplatform (BMAEF) is fabricated to perform on-demand destruction of mitochondria and golgi apparatus, which also generates the enhanced photothermal-immunotherapy, resulting in the effective inhibition of primary and metastasis tumor. The BMAEF has a core of mesoporous silica nanoparticles loaded with brefeldin A (BM), which is connected to ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA) and folic acid co-modified gold nanoparticles (AEF). During therapy, the BMAEF first accumulates in tumor cells via folic acid-induced targeting. Subsequently, the schiff base/ester bond cleaves in lysosome to release brefeldin A and AEF with exposed EGTA. The EGTA further captures Ca2+ to block ion transfer among mitochondria, endoplasmic reticulum, and golgi apparatus, which not only induced dysfunction of mitochondria and golgi apparatus assisted by brefeldin A to suppress both energy and material metabolism against tumor growth and metastasis, but causes AEF aggregation for tumor-specific photothermal therapy and photothermal assisted immunotherapy. Moreover, the dysfunction of these organelles also stops the production of BMI1 and heat shock protein 70 to further enhance the metastasis inhibition and photothermal therapy, which meanwhile triggers the escape of cytochrome C to cytoplasm, leading to additional apoptosis of tumor cells.

Incidence, characteristics, and risk factors of drug-associated muscle adverse reaction: a retrospective real-world study of inpatients.

OBJECTIVE: To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use. METHODS: We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses. RESULTS: Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs. CONCLUSION: Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life.

A case-control study on the clinical characteristics of granisetron-related arrhythmias and the development of a predictive nomogram.

BACKGROUND: Automatic monitoring and assessment are increasingly employed in drug safety evaluations using hospital information system data. The increasing concern about granisetron-related arrhythmias requires real-world studies to improve our understanding of its safety. AIM: This study aimed to analyze the incidence, clinical characteristics, and risk factors of granisetron-related arrhythmias in hospitalized patients using real-world data obtained from the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II) and concurrently aimed to develop and validate a nomogram to predict the occurrence of arrhythmias. METHOD: Retrospective automatic monitoring of inpatients using granisetron was conducted in a Chinese hospital from January 1, 2017, to December 31, 2021, to determine the incidence of arrhythmias using ADE-ASAS- II. Propensity score matching was used to balance confounders and analyze clinical characteristics. Based on risk factors identified through logistic regression analysis, a prediction nomogram was established and internally validated using the Bootstrap method. RESULTS: Arrhythmias occurred in 178 of 72,508 cases taking granisetron with an incidence of 0.3%. Independent risk factors for granisetron-related arrhythmias included medication duration, comorbid cardiovascular disease, concomitant use of other 5-hydroxytryptamine 3 receptor antagonists, alanine aminotransferase > 40 U/L, and blood urea nitrogen > 7.5 mmol/L. The nomogram demonstrated good differentiation and calibration, with enhanced clinical benefit observed when the risk threshold ranged from 0.10 to 0.82. CONCLUSION: The nomogram, based on the five identified independent risk factors, may be valuable in predicting the risk of granisetron-related arrhythmias in the administered population, offering significant clinical applications.

Psychromicrobium Xiongbiense sp. nov., an Actinobacterium Isolated from Forest Soil.

A novel Gram-stain-positive, oval-shaped, and non-flagellated bacterial strain YIM S02556T was isolated from forest soil in Xiongbi Town, Shizong County, Qujing City, Yunnan Province, southwestern China. The strain exhibited high pairwise 16 S rRNA gene sequence similarity with Psychromicrobium lacuslunae (97.3%) and Psychromicrobium silvestre (96.3%). Strain YIM S02556T exhibited an average nucleotide identity (ANI) of 72.5% with P. lacuslunae IHBB 11,108T and 72.8% ANI with P. silvestre AK 20-18T. The digital DNA-DNA hybridization (dDDH) value between strain YIM S02556T and P. lacuslunae IHBB 11,108T was 20.2%, while with P. silvestre AK 20-18T, the dDDH value was 20.8%. Strain YIM S02556T exhibited optimal growth at 28 °C, pH 7.0, without NaCl. Growth occurred within 10-37 ℃, pH 5.0-8.0, and in the presence of up to 5% w/v NaCl concentration. The genome size was 3.1 Mbp with 64.2% G + C content. The predominant menaquinone was MK-8(H4). The major cellular fatty acid was anteiso-C15:0. Based on the polyphasic analysis, strain YIM S02556T (= KCTC 49,805T = CCTCC AB2020166T) represents a novel Psychromicrobium species in which the name Psychromicrobium xiongbiense sp.nov. was proposed.

Targeting TOP2B as a vulnerability in aging and aging-related diseases.

The ongoing trend of rapid aging of the global population has unavoidably resulted in an increase in aging-related diseases. There is an immense amount of interest in the scientific community for the identification of molecular targets that may effectively mitigate the process of aging and aging-related diseases. The enzyme Topoisomerase IIß (TOP2B) plays a crucial role in resolving the topological challenges that occur during DNA-related processes. It is believed that the disruption of TOP2B function contributes to the aging of cells and tissues, as well as the development of age-related diseases. Consequently, targeting TOP2B appears to be a promising approach for interventions aimed at mitigating the effects of aging. This review focuses on recent advancements in the understanding of the role of TOP2B in the processing of aging and aging-related disorders, thus providing a novel avenue for the development of anti-aging strategies.

Targeting Trop2 by Bruceine D suppresses breast cancer metastasis by blocking Trop2/ß-catenin positive feedback loop.

INTRODUCTION: Tumor-associated calcium signal transducer 2 (Trop2) has been used as a transport gate for cytotoxic agents into cells in antibody-drug conjugate designs because of its expression in a wide range of solid tumors. However, the specific role of Trop2 itself in breast cancer progression remains unclear and small molecules targeting Trop2 have not yet been reported. OBJECTIVES: To screen small molecules targeting Trop2, and to reveal its pharmacological effects and the molecular mechanisms of action. METHODS: Small molecule targeting Trop2 was identified by cell membrane chromatography, and validated by cellular thermal shift assay and point mutation analyses. We investigated the pharmacological effects of Trop2 inhibitor using RNA-seq, human foreskin fibroblast (HFF)-derived extracellular matrix (ECM), Matrigel drop invasion assays, colony-forming assay, xenograft tumor model, 4T1 orthotopic metastasis model and 4T1 experimental metastasis model. The molecular mechanism was determined using immunoprecipitation, mass spectrometry, immunofluorescence, immunohistochemistry and Western blotting. RESULTS: Here we identified Bruceine D (BD) as the inhibitor of Trop2, and demonstrated anti-metastasis effects of BD in breast cancer. Notably, Lys307 and Glu310 residues of Trop2 acted as critical sites for BD binding. Mechanistically, BD suppressed Trop2-induced cancer metastasis by blocking the formation of Trop2/ß-catenin positive loop, in which the Trop2/ß-catenin complex prevented ß-catenin from being degraded via the ubiquitin-proteosome pathway. Destabilized ß-catenin caused by BD reduced nucleus translocation, leading to the reduction of transcription of Trop2, the reversal of epithelial-mesenchymal transition (EMT) process, and the inhibition of ECM remodeling, further inhibiting cancer metastasis. Additionally, the inhibitory effects of BD on lung metastatic colonization and the beneficial effects of BD on prolongation of survival were validated in 4T1 experimental metastasis model. CONCLUSIONS: These results support the tumor-promoting role of Trop2 in breast cancer by stabilizing ß-catenin in Trop2/ß-catenin positive loop, and suggest Bruceine D as a promising candidate for Trop2 inhibition.

Role and molecular regulatory mechanisms of Hippo signaling pathway in Caenorhabditis elegans and mammalian cell models of Alzheimer's disease.

Although there is increasing evidence for the involvement of Hippo signaling in Alzheimer's disease (AD), the detailed functions and regulatory mechanisms are not fully understood, given the diverse biological effects of this pathway. In the present work, we used Caenorhabditis elegans and mammalian cell models to investigate changes in the Hippo signaling pathway in response to Aß and the downstream effects on AD development. Aß1-42 production in the AD models decreased phosphorylation of the upstream CST-1/WTS-1 kinase cascade and promoted an interaction between LIN-10 and YAP-1, leading to the nuclear translocation of YAP-1 and inducing gene transcription in conjunction with the transcription factor EGL-44. The YAP-1/EGL-44 complex suppressed the autophagy-lysosome pathway by modulating mTOR signaling, which enhanced Aß1-42 accumulation and promoted AD progression. These results demonstrate for the first time that crosstalk between Hippo and mTOR signaling contributes to AD development by enhancing Aß production, resulting in inhibition of Hippo signaling and autophagy-lysosome pathway and Aß accumulation, suggesting potential therapeutic targets for the treatment or prevention of AD.

Multi-omics analyses reveal the importance of chromoplast plastoglobules in carotenoid accumulation in citrus fruit.

Chromoplasts act as a metabolic sink for carotenoids, in which plastoglobules serve as versatile lipoprotein particles. PGs in chloroplasts have been characterized. However, the features of PGs from non-photosynthetic plastids are poorly understood. We found that the development of chromoplast plastoglobules (CPGs) in globular and crystalloid chromoplasts of citrus is associated with alterations in carotenoid storage. Using Nycodenz density gradient ultracentrifugation, an efficient protocol for isolating highly purified CPGs from sweet orange (Citrus sinensis) pulp was established. Forty-four proteins were defined as likely comprise the core proteome of CPGs using comparative proteomics analysis. Lipidome analysis of different chromoplast microcompartments revealed that the nonpolar microenvironment within CPGs was modified by 35 triacylglycerides, two sitosterol esters, and one stigmasterol ester. Manipulation of the CPG-localized gene CsELT1 (esterase/lipase/thioesterase) in citrus calli resulted in increased lipids and carotenoids, which is further evidence that the nonpolar microenvironment of CPGs contributes to carotenoid accumulation and storage in the chromoplasts. This multi-feature analysis of CPGs sheds new light on the role of chromoplasts in carotenoid metabolism, paving the way for manipulating carotenoid content in citrus fruit and other crops.

Selective Manipulation of the Mitochondria Oxidative Stress in Different Cells Using Intelligent Mesoporous Silica Nanoparticles to Activate On-Demand Immunotherapy for Cancer Treatment.

Herein, the vitamin K2 (VK2)/maleimide (MA) coloaded mesoporous silica nanoparticles (MSNs), functional molecules including folic acid (FA)/triphenylphosphine (TPP)/tetrapotassium hexacyanoferrate trihydrate (THT), as well as CaCO3 are explored to fabricate a core-shell-corona nanoparticle (VMMFTTC) for on-demand anti-tumor immunotherapy. After application, the tumor-specific acidic environment first decomposed CaCO3 corona, which significantly levitates the pH value of tumor tissue to convert M2 type macrophage to the antitumor M1 type. The resulting VMMFTT would then internalize in both tumor cells and macrophages via FA-assisted endocytosis and free endocytosis, respectively. These distinct processes generate different amount of VMMFTT in above two cells followed by 1) TPP-induced accumulation in the mitochondria, 2) THT-mediated effective capture of various signal ions to cut off signal transmission and further inhibit glutathione (GSH) generation, 3) ions catalyzed reactive oxygen species (ROS) production through Fenton reaction, 4) sustained release of VK2 and MA to further enhance the ROS production and GSH depletion, which caused significant apoptosis of tumor cells and additional M2-to-M1 macrophage polarization via different processes of oxidative stress. Moreover, the primary tumor apoptosis further matures surrounding immature dendritic cells and activates T cells to continuously promote the antitumor immunotherapy.

The kiwifruit amyloplast proteome (kfALP): a resource to better understand the mechanisms underlying amyloplast biogenesis and differentiation.

The biogenesis and differentiation (B&D) of amyloplasts contributes to fruit flavor and color. Here, remodeling of starch granules, thylakoids and plastoglobules was observed during development and ripening in two kiwifruit (Actinidia spp.) cultivars - yellow-fleshed 'Hort16A' and green-fleshed 'Hayward'. A protocol was developed to purify starch-containing plastids with a high degree of intactness, and amyloplast B&D was studied using label-free-based quantitative proteomic analyses in both cultivars. Over 3000 amyloplast-localized proteins were identified, of which >98% were quantified and defined as the kfALP (kiwifruit amyloplast proteome). The kfALP data were validated by Tandem-Mass-Tag (TMT) labeled proteomics in 'Hort16A'. Analysis of the proteomic data across development and ripening revealed: 1) a conserved increase in the abundance of proteins participating in starch synthesis/degradation during both amyloplast B&D; 2) up-regulation of proteins for chlorophyll degradation and of plastoglobule-localized proteins associated with chloroplast breakdown and plastoglobule formation during amyloplast differentiation; 3) constitutive expression of proteins involved in ATP supply and protein import during amyloplast B&D. Interestingly, two different pathways of amyloplast B&D were observed in the two cultivars. In 'Hayward', significant increases in abundance of photosynthetic- and tetrapyrrole metabolism-related proteins were observed, but the opposite trend was observed in 'Hort16A'. In conclusion, analysis of the kfALP provides new insights into the potential mechanisms underlying amyloplast B&D with relevance to key fruit quality traits in contrasting kiwifruit cultivars.

Altered cognitive control network mediates the association between long-term pain and anxiety symptoms in primary dysmenorrhea.

Neuroimaging studies have demonstrated the association of the cognitive control network (CCN) with the maintenance of chronic pain. However, whether and how dorsolateral prefrontal cortex (DLPFC), a key region within the CCN, is altered in menstrual pain is unclear. In this study, we aimed to investigate alterations in the DLPFC functional connectivity network in patients with primary dysmenorrhea (PDM). The study comprised 41 PDM patients and 39 matched healthy controls (HCs), all of whom underwent a resting-state functional MRI scan during the menstrual stage. All participants were instructed to complete the clinical assessment before the MRI scan. We used the DLPFC as the seed in resting-state functional connectivity (rsFC) analysis to investigate the difference between PDM patients and HCs. Compared to HCs, PDM patients showed increased right DLPFC rsFC at the bilateral lingual gyrus, dorsal anterior cingulate cortex (dACC), and middle cingulate cortex, and decreased left DLPFC rsFC at the right orbital frontal cortex. In addition, increased right DLPFC-bilateral dACC connectivity mediated the association between disease duration and the self-rating anxiety scale (SAS) scores in PDM patients. We confirmed that the DLPFC-dACC rsFC was associated with higher SAS scores, which could mediate the association between disease duration and anxiety symptoms in patients with PDM. Our findings provide central pathological evidence for an abnormal rsFC of the CCN in PDM patients, which may contribute to a better understanding of the neuropathophysiological mechanisms underlying PDM.

Synthesis of Bridged Cycloisoxazoline Scaffolds via Rhodium-Catalyzed Coupling of Nitrones with Cyclic Carbonate.

Bridged isoxazolidines were synthesized via Rh(III)-catalyzed C-H allylation of α-aryl nitrones with 5-methylene-1,3-dioxan-2-one. The nitrone group serves as a directing group and 1,3-dipole in the C-H activation/[3 + 2] cycloaddition cascade, exhibiting excellent chemo- and stereoselectivity along with good functional group compatibility. The resulting skeletal structure was conveniently modified to produce a range of important chemical frameworks, and the protocol was applied to biologically active molecules.

Co-infection of Chlamydia psittaci and Tropheryma whipplei: A case report.

BACKGROUND: The co-infection of Chlamydia psittaci (C. psittaci) and Tropheryma whipplei (T. whipplei) is unusual, and the detection of pathogenic microorganisms is particularly important for patients with severe diseases or poor experience in treatment. Early identification of pathogens can significantly improve the prognosis of the patients. Targeted next-generation sequencing (tNGS) is currently widely used in clinical practice for various infectious diseases, including respiratory infections, to achieve early, accurate, and rapid microbial diagnosis. CASE SUMMARY: We report a case of a 40-year-old female patient with a history of contact with parrots who was diagnosed with C. psittaci and T. whipplei infection through bronchial lavage fluid targeted next generation sequencing. After moxifloxacin treatment, the patient's symptoms improved significantly, and the imaging changes were obviously resolved. CONCLUSION: Coinfection with C. psittaci and T. whipplei is not common. In this case, timely and accurate identification of both pathogens was achieved using tNGS. Moreover, the efficacy of monotherapy with moxifloxacin was confirmed.

Health system barriers to timely routine measles vaccinations in rural southwest China: a qualitative study on the perspectives of township vaccination professionals and village doctors.

OBJECTIVES: A well-functioning health system ensures timely routine measles vaccinations for age-appropriate children, minimising measles risk. However, there is limited knowledge about the impact of the performance of immunisation programmes in health systems on the timeliness of measles vaccination. This study aimed to identify health system barriers to timely routine measles vaccination in rural southwest China, integrating the perspectives of township vaccination professionals and village doctors. DESIGN, SETTING AND PARTICIPANTS: Qualitative study among township vaccination professionals and village doctors in rural Guangxi, southwest China. METHODS: 20 focus group discussions (FGDs) at township level and 120 in-depth interviews (IDIs) at village level, based on a four-theme framework. We used convenience sampling to recruit 60 township vaccination professionals and 120 village doctors in 2015. Instruments used were a semistructured questionnaire and interview outlines. We collected township and village-level data focusing on themes of health resources allocation, pattern of vaccination services, management and supervision of vaccination services, and perceptions of vaccination policy. The FGDs and IDIs were audio-recorded and transcribed. Braun and Clarke's thematic analysis approach was adopted to synthesise findings into meaningful subthemes, narrative text and illustrative quotations. RESULTS: The health system barriers to timely routine vaccinations were explored across four themes. Barriers in the health resources allocation theme comprised (1) inadequacy of vaccination-related human resources (eg, lack of township vaccination professionals and lack of young village doctors), and (2) incompatible and non-identical information system of vaccination services across regions. Barriers in the pattern of vaccination services theme included inflexible vaccination services models, for example, routine vaccination services being offered monthly on fixed vaccination days, limited numbers of vaccination days per month, vaccination days being set on non-local market days, vaccination days being clustered into a specific period and absence of formal vaccination appointments. Ineffective economic incentive mechanism was identified as a barrier in the management and supervision of vaccination services theme. Low-degree participation of village doctors in routine vaccination services was identified as a barrier in the perceptions of vaccination policy theme. CONCLUSIONS: We encourage policymakers and stakeholders to apply these findings to improve the timeliness of routine vaccination. Barriers to timely routine vaccination include inadequate allocation of vaccination-related resources and inflexible vaccination service delivery models. Financial and non-financial incentives should be used to retain and recruit vaccination professionals and village doctors. Strengthening information systems with unified data standards enables cross-regional data exchange. Optimising immunisation services and rationalising vaccination days could eliminate health system barriers and improve vaccination timeliness in rural China.

Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

[Evolution Characteristics of Atmospheric Formaldehyde Emissions in Guangdong Province from 2006 to 2020].

Atmospheric formaldehyde, a key precursor for ozone (O3) and secondary PM2.5, is carcinogenic and plays an important role in atmospheric photochemistry and the formation of secondary pollution. However, the lack of understanding of the emission sources of atmospheric formaldehyde limits the study on the formation mechanism of secondary pollution and the formulation of pollution control strategies. This study used the emission factor and source profile methods to establish the emission inventories of formaldehyde in Guangdong Province from 2006 to 2020 and identified the main emission sources of formaldehyde and spatial and temporal evolution characteristics. The results showed that the formaldehyde emissions in Guangdong Province fluctuated in the range of 39000-56000 tons during 2006 to 2020, exhibiting a very weak downward trend. Biomass combustion is an important source of formaldehyde emission in Guangdong Province, of which the contribution decreased from 58% in 2006 to 27% in 2020 owing to effective control measures implemented in Guangdong Province. The solvent use source became the predominant emission source of formaldehyde in 2020 by contributing up to 28%, primarily through plastic products and asphalt paving sources. The construction machinery and trucks fueled by diesel were important contributors of formaldehyde emissions from mobile sources. Although the formaldehyde emissions in the Pearl River Delta and the non-Pearl River Delta were equivalent, the spatial distributions showed that formaldehyde emission hotspots were concentrated in the center of the Pearl River Delta and the eastern and western areas of the non-Pearl River Delta. This was primarily because the solvent use and mobile sources were the main sources of formaldehyde emissions in the Pearl River Delta, whereas the biomass combustion source was the dominant source in the non-Pearl River Delta. Therefore, the formaldehyde emission mitigations of the industrial and mobile sources in the central region of the Pearl River Delta and the biomass combustion source in the western area of Guangdong should be further strengthened in the future.

Self-reported critical gaps in the essential knowledge and capacity of spatial epidemiology between the current university education and competency-oriented professional demands in preparing for a future pandemic among public health postgraduates in China: a nationwide cross-sectional survey.

BACKGROUND: Spatial epidemiology plays an important role in public health. Yet, it is unclear whether the current university education in spatial epidemiology in China could meet the competency-oriented professional demands. This study aimed to understand the current situation of education and training, practical application, and potential demands in spatial epidemiology among public health postgraduates in China, and to assess the critical gaps in a future emerging infectious diseases (EID) pandemic preparedness and response. METHODS: This study was divided into three parts. The first part was a comparative study on spatial epidemiology education in international public health postgraduate training. The second part was a cross-sectional survey conducted among public health professionals. The third part was a nationwide cross-sectional survey conducted among public health postgraduates at Chinese universities from October 2020 to February 2021. Data was collected by the WeChat-based questionnaire star survey system and analyzed using the SPSS software. RESULTS: International education institutions had required public health postgraduates to master the essential knowledge and capacity of spatial epidemiology. A total of 198 public health professionals were surveyed, and they had a median of 4.00 (IQR 3.13-4.53) in demand degree of spatial epidemiology. A total of 1354 public health postgraduates were surveyed from 51 universities. Only 29.41% (15/51) of universities offered spatial epidemiology course. Around 8.05% (109/1354) of postgraduates had learned spatial epidemiology, and had a median of 1.05 (IQR 1.00-1.29) in learning degree and a median of 1.91 (IQR 1.05-2.78) in practical application degree of spatial epidemiology. To enhance professional capacity, 65.95% (893/1354) of postgraduates hoped that universities would deliver a credit-course of spatial epidemiology. CONCLUSIONS: A huge unmet education and training demand in spatial epidemiology existed in the current education system of public health postgraduates in China. To enhance the competency-oriented professional capacity in preparedness and response to a future pandemic, it is urgent to incorporate the teaching and training of spatial epidemiology into the compulsory curriculum system of public health postgraduates in China.

Implantable Hydrogel-Protective DNA Aptamer-Based Sensor Supports Accurate, Continuous Electrochemical Analysis of Drugs at Multiple Sites in Living Rats.

The ability to track the levels of specific molecules, such as drugs, metabolites, and biomarkers, in the living body, in real time and for long durations, would improve our understanding of health and our ability to diagnose, treat, and monitor disease. To this end, we are developing electrochemical aptamer-based (EAB) biosensors, a general platform supporting high-frequency, real-time molecular measurements in the living body. Here we report that the use of an agarose hydrogel protective layer for EAB sensors significantly improves their signaling stability when deployed in the complex, highly time-varying environments found in vivo. The improved stability is sufficient that these hydrogel-protected sensors achieved good baseline stability and precision when deployed in situ in the veins, muscles, bladder, or tumors of living rats without the use of the drift correction approaches traditionally required in such placements. Finally, our implantable gel-protective EAB sensors achieved good biocompatibility when deployed in vivo in the living rats without causing any severe inflammation.

Homoharringtonine sensitizes pancreatic cancer to erlotinib by direct targeting and miRNA-130b-3p-mediated EphB4-JAK2-STAT3 axis.

OBJECTIVES: Pancreatic cancer (PC) is a very lethal malignancy with a scarcity of treatment options. Although erlotinib- and gemcitabine-based treatments have been approved for PC, their effectiveness is limited. The present study is aimed at exploring the molecular and epigenetic mechanisms of anticancer activities of homoharringtonine (HHT) and its interaction with erlotinib to develop a potential therapeutic strategy for PC. METHODS: The RT-qPCR, western blotting, immunofluorescence and expression-vectors and oligonucleotide transfection were employed to determine the expression characteristics of onco-factors. Anticancer activities were determined by MTT, colony forming, and flowcytometric analysis. Dual luciferase assay was conducted to confirm putative target of miR-130b-3p. In-vivo experiments were followed by immunohistochemical assay. KEY FINDINGS: The EphB4/JAK2/STAT3 pathway drives the growth and proliferation of PC through induction of prosurvival factors and cell cycle mediators. HHT directly and epigenetically via miR-130b-3p targets EphB4, leading to downregulation of JAK2/STAT3 pathway. The inactivation of STAT3 results in diminution of antiapoptotic factors and cell cycle mediators. HHT also enhances the anticancer activity of erlotinib. CONCLUSIONS: HHT demonstrates potential anticancer activities in PC by downregulating EphB4/JAK2/STAT3 signalling. HHT also produces synergistic effects with erlotinib.