Emission characteristics, environmental impacts and health risk assessment of volatile organic compounds from the typical chemical industry in China.

To study the volatile organic compounds (VOCs) emission characteristics of industrial enterprises in China, 6 typical chemical industries in Yuncheng City were selected as research objects, including the modern coal chemical industry (MCC), pharmaceutical industry (PM), pesticide industry (PE), coking industry (CO) and organic chemical industry (OC). The chemical composition of 91 VOCs was quantitatively analyzed. The results showed that the emission concentration of VOCs in the chemical industry ranged from 1.16 to 155.59 mg/m3. Alkanes were the main emission components of MCC (62.0%), PE (55.1%), and OC (58.5%). Alkenes (46.5%) were important components of PM, followed by alkanes (23.8%) and oxygenated volatile organic compounds (OVOCs) (21.2%). Halocarbons (8.6%-71.1%), OVOCs (9.7%-37.6%) and alkanes (11.2%-27.0%) were characteristic components of CO. The largest contributor to OFP was alkenes (0.6%-81.7%), followed by alkanes (9.3%-45.9%), and the lowest one was alkyne (0%-0.5%). Aromatics (66.9%-85.4%) were the largest contributing components to SOA generation, followed by alkanes (2.6%-28.5%), and the lowest one was alkenes (0%-4.1%). Ethylene and BTEX were the key active species in various chemical industries. The human health risk assessment showed workers long-term exposed to the air in the chemical industrial zone had a high cancer and non-cancer risk during work, and BTEX and dichloromethane were the largest contributors.

Simulation of Frost-Heave Failure of Air-Entrained Concrete Based on Thermal-Hydraulic-Mechanical Coupling Model.

The internal pore structural characteristics and microbubble distribution features of concrete have a significant impact on its frost resistance, but their size is relatively small compared to aggregates, making them difficult to visually represent in the mesoscopic numerical model of concrete. Therefore, based on the ice-crystal phase transition mechanism of pore water and the theory of fine-scale inclusions, this paper establishes an estimation model for effective thermal conductivity and permeability coefficients that can reflect the distribution characteristics of the internal pore size and the content of microbubbles in porous media and explores the evolution mechanism of effective thermal conductivity and permeability coefficients during the freezing process. The segmented Gaussian integration method is adopted for the calculation of integrals involving pore size distribution curves. In addition, based on the concept that the fracture phase represents continuous damage, a switching model for the permeability coefficient is proposed to address the fundamental impact of frost cracking on permeability. Finally, the proposed estimation models for thermal conductivity and permeability are applied to the cement mortar and the interface transition zone (ITZ), and a thermal-hydraulic-mechanical coupling finite element model of concrete specimens at the mesoscale based on the fracture phase-field method is established. After that, the frost-cracking mechanism in ordinary concrete samples during the freezing process is explored, as well as the mechanism of microbubbles in relieving pore pressure and the adverse effect of accelerated cooling on frost cracking. The results show that the cracks first occurred near the aggregate on the concrete sample surface and then extended inward along the interface transition zone, which is consistent with the frost-cracking scenario of concrete structures in cold regions.

Synthesis of non-canonical amino acids through dehydrogenative tailoring.

Amino acids are essential building blocks in biology and chemistry. While nature relies on a small number of amino acid structures, chemists desire access to a vast scope of structurally diverse analogs1-3 The selective modification of amino acid side-chain residues represents an efficient strategy to access non-canonical derivatives of value in chemistry and biology. While semi-synthetic methods leveraging the functional groups found in polar and aromatic amino acids have been extensively explored, highly selective and general approaches to transform unactivated C-H bonds in aliphatic amino acids remain less developed4,5 Here, we disclose a stepwise dehydrogenative method to convert aliphatic amino acids into structurally diverse analogs. The key to the success of this approach lies in the development of a selective catalytic acceptorless dehydrogenation method driven by photochemical irradiation, which provides access to terminal alkene intermediates for downstream functionalization. Overall, this strategy enables the rapid synthesis of new amino acid building blocks and suggests possibilities for the late-stage modification of more complex oligopeptides.

Screening of tumor antigens and immunogenic cell death landscapes of prostate adenocarcinoma for exploration of mRNA vaccine.

BACKGROUND: In this study, effective antigens of mRNA vaccine were excavated from the perspective of ICD, and ICD subtypes of PRAD were further distinguished to establish an ICD landscape, thereby determining suitable vaccine recipients. RESEARCH DESIGN AND METHODS: TCGA and MSKCC databases were applied to acquire RNA-seq data and corresponding clinical data of 554 and 131 patients, respectively. GEPIA was employed to measure prognostic indices. Then, a comparison of genetic alterations was performed utilizing cBioPortal, and correlation of identified ICD antigens with immune infiltrating cells was analyzed employing TIMER. Moreover, ICD subtypes were identified by means of consensus cluster, and ICD landscape of PRAD was depicted utilizing graph learning-based dimensional reduction. RESULTS: In total, 4 PRAD antigens were identified in PRAD, including FUS, LMNB2, RNPC3, and ZNF700, which had association with adverse prognosis and infiltration of APCs. PRAD patients were classified as two ICD subtypes based on their differences in molecular, cellular, and clinical features. Furthermore, ICD modulators and immune checkpoints were also differentially expressed between two ICD subtype tumors. Finally, the ICD landscape of PRAD showed substantial heterogeneity among individual patients. CONCLUSIONS: In summary, the research may provide a theoretical foundation for developing mRNA vaccine against PRAD as well as determining appropriate vaccine recipients.

Rag-Ragulator is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway.

The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth and metabolism in response to many environmental cues, including nutrients. Amino acids signal to mTORC1 by modulating the guanine nucleotide loading states of the heterodimeric Rag GTPases, which bind and recruit mTORC1 to the lysosomal surface, its site of activation. The Rag GTPases are tethered to the lysosome by the Ragulator complex and regulated by the GATOR1, GATOR2, and KICSTOR multiprotein complexes that localize to the lysosomal surface through an unknown mechanism(s). Here, we show that mTORC1 is completely insensitive to amino acids in cells lacking the Rag GTPases or the Ragulator component p18. Moreover, not only are the Rag GTPases and Ragulator required for amino acids to regulate mTORC1, they are also essential for the lysosomal recruitment of the GATOR1, GATOR2, and KICSTOR complexes, which stably associate and traffic to the lysosome as the "GATOR" supercomplex. The nucleotide state of RagA/B controls the lysosomal association of GATOR, in a fashion competitively antagonized by the N terminus of the amino acid transporter SLC38A9. Targeting of Ragulator to the surface of mitochondria is sufficient to relocalize the Rags and GATOR to this organelle, but not to enable the nutrient-regulated recruitment of mTORC1 to mitochondria. Thus, our results reveal that the Rag-Ragulator complex is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway and underscore that mTORC1 activation requires signal transduction on the lysosomal surface.

Dual electrochemical signal "signal-on-off" sensor based on CHA-Td-HCR and CRISPR-Cas12a for MUC1 detection.

Mucin 1 (MUC1) is frequently overexpressed in various cancers and is essential for early cancer detection. Current methods to detect MUC1 are expensive, time-consuming, and require skilled personnel. Therefore, developing a simple, sensitive, highly selective MUC1 detection sensor is necessary. In this study, we proposed a novel "signal-on-off" strategy that, in the presence of MUC1, synergistically integrates catalytic hairpin assembly (CHA) with DNA tetrahedron (Td)-based nonlinear hybridization chain reaction (HCR) to enhance the immobilization of electrochemically active methylene blue (MB) on magnetic nanoparticles (MNP), marking the MB signal "on". Concurrently, the activation of CRISPR-Cas12a by isothermal amplification products triggers the cleavage of single-stranded DNA (ssDNA) at the electrode surface, resulting in a reduction of MgAl-LDH@Fc-AuFe-MIL-101 (containing ferrocene, Fc) on the electrode, presenting the "signal-off" state. Both MB and MgAl-LDH@Fc-AuFe-MIL-101 electrochemical signals were measured and analyzed. Assay parameters were optimized, and sensitivity, stability, and linear range were assessed. Across a concentration spectrum of MUC1 spanning from 10 fg/mL to 100 ng/mL, the MB and MgAl-LDH@Fc-AuFe-MIL-101 signals were calibrated with each other, demonstrating a "signal-on-off" dual electrochemical signaling pattern. This allows for the precise and quantitative detection of MUC1 in clinical samples, offering significant potential for medical diagnosis.

Considering multi-scale built environment in modeling severity of traffic violations by elderly drivers: An interpretable machine learning framework.

The causes of traffic violations by elderly drivers are different from those of other age groups. To reduce serious traffic violations that are more likely to cause serious traffic crashes, this study divided the severity of traffic violations into three levels (i.e., slight, ordinary, severe) based on point deduction, and explore the patterns of serious traffic violations (i.e., ordinary, severe) using multi-source data. This paper designed an interpretable machine learning framework, in which four popular machine learning models were enhanced and compared. Specifically, adaptive synthetic sampling method was applied to overcome the effects of imbalanced data and improve the prediction accuracy of minority classes (i.e., ordinary, severe); multi-objective feature selection based on NSGA-II was used to remove the redundant factors to increase the computational efficiency and make the patterns discovered by the explainer more effective; Bayesian hyperparameter optimization aimed to obtain more effective hyperparameters combination with fewer iterations and boost the model adaptability. Results show that the proposed interpretable machine learning framework can significantly improve and distinguish the performance of four popular machine learning models and two post-hoc interpretation methods. It is found that six of the top ten important factors belong to multi-scale built environment attributes. By comparing the results of feature contribution and interaction effects, some findings can be summarized: ordinary and severe traffic violations have some identical influencing factors and interactive effects; have the same influencing factors or the same combinations of influencing factors, but the values of the factors are different; have some unique influencing factors and unique combinations of influencing factors.

Electrochemical-Fluorescent Bimodal Biosensor Based on Dual CRISPR-Cas12a Multiple Cascade Amplification for ctDNA Detection.

Circulating tumor DNA (ctDNA) is a critical biomarker for early tumor detection. However, accurately quantifying low-abundance ctDNA in human serum remains a significant challenge. To address this challenge, we introduce a bimodal biosensor tailored for detecting the epidermal growth factor receptor (EGFR) mutation L858R in specific nonsmall cell lung cancer (NSCLC) patients. This biosensor utilizes dual CRISPR-Cas12a systems to quantify the target via fluorescence and electrochemical signals. In our system, the EGFR L858R exhibits resistance to digestion by the restriction enzyme MscI, which activates the first CRISPR-Cas12a protein and inhibits the binding of magnetic beads with fluorescein (FAM)-labeled hybridization chain reaction (HCR) products, thereby reducing the fluorescence signal. This activation also inhibits the cleavage activity of the second CRISPR-Cas12a protein, allowing the electrode to sustain a higher electrochemical signal from nanomaterials. The wild-type EGFR (wt EGFR) produces the opposite effect. Consequently, the concentration of EGFR L858R can be accurately quantified and verified using both fluorescence and electrochemical signals. The biosensor offers a dynamic detection ranging from 10 fM to 1 µM, with a detection limit of 372 aM. It demonstrates excellent specificity, reproducibility, stability, and recovery rates. Moreover, the sensor's enhanced analytical sensitivity highlights its critical role in biosensing applications and early disease diagnosis.

CDK5RAP3 Inhibition by Hypoxia Activates P38MAPK to Facilitate Angiogenesis.

CDK5RAP3 is a recognized tumor suppressor that inhibits Chk1 and Chk2 and activates p53, all of which are involved with mediating toxin-induced apoptosis of cancer cells. CDK5RAP3 also inhibits p38MAPK phosphorylation and activity via mediating a p38 interaction with wild-type p53-induced phosphatase 1. This study aimed to investigate the antiangiogenic activity of CDK5RAP3 and its molecular mechanisms in human umbilical vein endothelial cells (HUVECs) under conditions of hypoxic conditions. Angiogenesis was induced in HUVECs mainly by vascular endothelial growth factor (VEGF). The CDK5RAP3 levels of HUVECs were reduced in a time-dependent manner in response to hypoxic treatment at 2% O2. The reduction of CDK5RAP3 was accompanied with increased p38MAPK phosphorylation and activation. Moderate hypoxia was found to significantly increase secreted VEGF concentrations, and the hypoxic conditioned medium (HCM) markedly enhanced proliferation, migration, and tube formation. Our findings indicate that moderate hypoxia facilitates angiogenesis by inhibiting CDK5RAP3. CDK5RAP3 exhibits a clear regulatory role in vascular regeneration, as downregulating its expression in endothelial cells enhances VEGF synthesis and subsequently improves cell migration and lumen formation capability. This study presents evidence indicating that moderate hypoxia facilitates angiogenesis by inhibiting CDK5RAP3, demonstrating the potential for CKD5RAP3 to be a potent antiangiogenic agent in angiogenesis regulation of cancer, ischemic diseases, and wound healing.

The Effect of Dietary Fiber on Hyperkalemia in Maintenance Hemodialysis Patients: A Cross-Sectional Study.

OBJECTIVE: To explore the relationship between dietary fiber (DF) intake and hyperkalemia in maintenance hemodialysis (MHD) patients. METHODS: A total of 110 MHD patients were included, including 67 males and 43 females. Patients were divided into normal serum potassium group (N) and a hyperkalemia group (H) according to the serum potassium level before dialysis. The daily diet was recorded by the 3-day dietary recording method. The daily dietary nutrient intake of patients was analyzed. Logistic regression was used to analyze the relationship between hyperkalemia and DF intake. A receiver operating characteristic curve was used to analyze the cutoff value of DF intake to prevent hyperkalemia. RESULTS: Of the 110 patients, 38 had hyperkalemia (serum potassium >5.5 mmol/L) before dialysis. There was no difference in sex, residual kidney function, body mass index, energy intake, fat intake, protein intake, calcium intake, sodium intake, phosphorus intake or the administration history of potassium-lowering drugs between the 2 groups (P > .05). Compared with the H group, patients in the N group had higher carbohydrate intake (315 ± 76 g/d vs. 279 ± 66 g/d, P = .016), dietary fiber intake (19 ± 5 g/d vs. 12 ± 8 g/d, P < .0001), and potassium intake (1,698 ± 392 mg/d vs. 1,533 ± 413 mg/d, P = .041), and more patients in group N used renin-angiotensin-aldosterone system inhibitors (52.78% vs. 23.68%, P = .003). However, the number of patients with constipation in group N was less than that in group H (20.83% vs. 42.11%, P = .018). Logistic regression analysis showed that DF intake was an independent protective factor for hyperkalemia [P < .0001, odds ratio = 0.766 (95% confidence intervals: 0.675-0.870)]. Receiver operating characteristic analysis showed that daily intake of DF greater than 15.33 g may be helpful to prevent hyperkalemia. CONCLUSION: Insufficient dietary nutrient intake is prevalent in MHD patients, especially DF intake, which may be associated with hyperkalemia. Clinically, attention should be given to the dietary balance of MHD patients, especially DF intake.

Chinese herbal formula, modified Guilu Erxian glue, alleviates apoptosis of hematopoietic stem cells by regulating SLAM-SAP signal pathway in aplastic anemia mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Guilu Erxian Glue (GEG) and Danggui Buxue Tang (DBT) are traditional Chinese herbal formulas. According to the theory of traditional Chinese medicine, the combination of those two formulas (Modified Guilu Erxian Glue, MGEG) has the effects of tonifying the kidney and producing blood, was usually used to treat bone marrow failure diseases, including aplastic anemia (AA). AIM OF THE STUDY: T lymphocytes play a crucial role in the disease pathogenesis and progression of AA. Our preliminary results confirmed that GEG can improve the damage of hematopoietic stem cells in mice, while DBT can reduce the proliferation and differentiation of T lymphocytes and inhibit the production of IFN-γ. We hypothesized that the combination of those two herbal formulas could inhibit immune attack and restore hematopoietic function through multiple mechanisms. In this study, we aim to study the curative effect of MGEG on regulating the expression of Signal lymphocyte activating molecule (SLAM), an activation-related molecule in T lymphocytes, thereby suppressing the immune function of T cells and decelerating the damage to hematopoietic stem cells. MATERIALS AND METHODS: High-performance liquid chromatography-electrospray ionization/mass spectrometry system was used to identify the components of the MGEG formulation. Induction of aplastic anemia mouse model by injecting allogeneic lymphocyte suspension into BABL/c mice after ionizing radiation. Cyclosporine A (CsA) was used as a positive control drug. Flow cytometry was used to detect the number and apoptosis rate of hematopoietic stem cells in the bone marrow. Enzyme-linked immunosorbent assay was performed to measure the levels of IFN-γ and TNF-α. Immunofluorescence staining was used to assess the expression of T-bet and SLAM-SAP. Western Blot was conducted to examine the expression of activation-related molecules in T lymphocytes and proteins related to the Fas signal pathway. Hematoxylin-eosin staining was performed to observe pathological changes in the bone marrow tissue. Wright-Giemsa staining was utilized to evaluate alterations in the cellular composition and basic structure of the bone marrow cells (BMCs). Transmission electron microscopy was employed to observe changes in the structure and morphology of hematopoietic stem cells. The hematology analyzer was used to detect peripheral blood parameters. RESULTS: Twenty-three different components were identified in MGEG. After MGEG treatment, the expression levels of Fyn and SLAM-SAP binding were increased in AA mice, while the expression levels of T-bet were decreased and the secretion of IFN-γ was reduced significantly. Additionally, MGEG also could downregulate the protein levels of Fas, caspase-3, and cleaved caspase-3 in AA mice. CONCLUSION: MGEG could attenuate the production of IFN-γ by promoting the SLAM-SAP signal pathway to regulate the generation and distribution of T-bet in T cells. Additionally, it suppresses apoptosis of HSCs through intervention in the Fas-dependent pathway, thereby mitigating immune-mediated damage to HSCs.

[Construction and application of sepsis bundle therapy management and practice program].

OBJECTIVE: To construct a bundled therapy management and practice program for sepsis and explore its clinical application effect. METHODS: (1) Construction of sepsis bundled therapy management and practice program: a project team was established to conduct literature review, select experts, compile and distribute questionnaires, organize, analyze expert opinions, and ensure quality control throughout the research process. From October to November 2022, expert letter consultation was carried out, and questionnaires were distributed and collected by on-site filling and WeChat. The Likert 5-point scale was used to rate each item. (2) Clinical application of the protocol: ninety patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Xinjiang Medical University from January to July 2022 were retrospectively selected as the control group, and routine bundle treatment and nursing strategy for sepsis were adopted. Ninety patients with sepsis admitted from January to July 2023 were prospectively selected as the intervention group. Based on the treatment and nursing strategy of the control group, sepsis bundled therapy management and practice program constructed using the Delphi inquiry method was implemented. The completion rate of 1-hour, 3-hour and 6-hour bundle, the levels of inflammatory indicators at 1, 3, 7 days of treatment, and prognostic indicators were compared between the two groups. RESULTS: (1) Construction of sepsis bundled therapy management and practice program: the final plan consists of 4 primary indicators, 15 secondary indicators and 34 tertiary indicators. The response rates for both rounds of inquiry questionnaires were 100%. The coefficients of expert authority value were 0.948 and 0.940, respectively. The coefficient of variation for each item was 0-0.287 and 0-0.187, respectively. Kendall's W coefficients were 0.242 and 0.249, respectively, with statistical significances (all P < 0.05). (2) Clinical application of the protocol: there were no statistically significant differences in baseline data such as age, gender, infection site, pathogen species, duration of mechanical ventilation, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II) between the two groups. The completion rate of 1-hour, 3-hour and 6-hour bundle in the intervention group were higher than those in the control group (1-hour bundle completion rate: 53.30% vs. 21.10%, 3-hour bundle completion rate: 92.20% vs. 80.00%, 6-hour bundle completion rate: 88.89% vs. 65.56%, all P < 0.05). The levels of C-reactive protein (CRP), white blood cell count (WBC), procalcitonin (PCT), and interleukin-6 (IL-6) in two groups of patients showed statistically significant differences at different time points, between groups, and in interaction effects. Compared with the control group, the length of ICU stay in the intervention group was significantly shortened [days: 7.00 (4.00, 14.00) vs. 8.00 (7.00, 20.00), P < 0.01], and the hospitalization cost of ICU was significantly reduced [ten thousand yuan: 4.63 (3.36, 6.19) vs. 6.46 (3.32, 11.34), P < 0.05]. The 28-day mortality in the intervention group was lower than that in the control group (33.33% vs. 46.67%), but the difference was not statistically significant (P > 0.05). CONCLUSIONS: The constructed bundled therapy management and practice program for sepsis can improve the completion rate of bundle treatment, shorten the length of ICU stay of sepsis patients, reduce the hospitalization cost in ICU, and have a tendency to reduce the 28-day mortality.

Clinical spectrum of late symptomatic neurosyphilis in China: an 11-year retrospective study.

OBJECTIVES: This study aimed to describe the clinical features of neurosyphilis in Chinese patients in an attempt to find clinical features that are helpful for the early identification of neurosyphilis. METHODS: This retrospective study included people with syphilis who visited Shanghai Skin Disease Hospital between January 2010 and December 2020. Lumbar puncture was performed on those who met the inclusion and exclusion criteria. The diagnosis of neurosyphilis was based on clinical and laboratory findings. The parameters were analysed statistically. RESULTS: Of the 3524 patients with neurosyphilis, 2111 (59.9%) and 1413 (40.1%) were asymptomatic and symptomatic neurosyphilis, respectively. General paresis was the most common type of symptomatic neurosyphilis (46.8%). The clinical manifestations of symptomatic neurosyphilis include psychiatric and neurotic symptoms, among which general paresis predominantly presented as psychiatric symptoms such as affective (66.7%) and memory disorder (72.9%). Tabes dorsalis is often presented as neurotic symptoms. One hundred fifty patients (10.6%) with symptomatic neurosyphilis presented candy signs, a rare and specific neurosyphilis symptom that is common in general paresis. Girdle sensation was presented in 13 patients, mainly with tabes dorsalis, which had not been reported in previous studies. CONCLUSIONS: Notably, the candy sign is identified as a specific symptom of general paresis, while girdle sensations are highlighted as a particular symptom of tabes dorsalis. This is the largest study describing the clinical spectrum of neurosyphilis since the onset of the penicillin era and could help doctors learn more about the disease. A comprehensive description of the possible clinical manifestations of late symptomatic neurosyphilis, particularly highlighting rare symptoms, can identify suspicious patients and prevent diagnostic delays.

Natural variation in BnaA07.MKK9 confers resistance to Sclerotinia stem rot in oilseed rape.

Sclerotinia stem rot (SSR), caused by the necrotrophic fungus Sclerotinia sclerotiorum, is one of the most devastating diseases for several major oil-producing crops. Despite its impact, the genetic basis of SSR resistance in plants remains poorly understood. Here, through a genome-wide association study, we identify a key gene, BnaA07. MKK9, that encodes a mitogen-activated protein kinase kinase that confers SSR resistance in oilseed rape. Our functional analyses reveal that BnaA07.MKK9 interacts with BnaC03.MPK3 and BnaC03.MPK6 and phosphorylates them at the TEY activation motif, triggering a signaling cascade that initiates biosynthesis of ethylene, camalexin, and indole glucosinolates, and promotes accumulation of H2O2 and the hypersensitive response, ultimately conferring resistance. Furthermore, variations in the coding sequence of BnaA07.MKK9 alter its kinase activity and improve SSR resistance by ~30% in cultivars carrying the advantageous haplotype. These findings enhance our understanding of SSR resistance and may help engineer novel diversity for future breeding of oilseed rape.

A Case of Perianal Annular Rash: Atypical Presentation of Recurrent Secondary Syphilis.

Syphilis is a complex, systemic infectious disease caused by Treponema pallidum subspecies pallidum. Secondary syphilitic lesions typically manifest within 3 months following initial exposure to T. pallidum. The predominant cutaneous manifestations of secondary syphilis are macula and papule. Certain individuals with syphilis may present with an atypical rash during the secondary stage owing to immunosuppression and other factors. Herein, we report a rare case of atypical recurrent secondary syphilis around the anus in a 65-year-old woman. Based on cerebrospinal fluid findings and skin biopsy results, the patient was ultimately diagnosed as neurosyphilis and recurrent secondary syphilis. Following intravenous antibiotic therapy, the patient's rash improved significantly. This case underscores the importance for physicians to remain vigilant regarding the possibility of syphilis when encountering cases exhibiting unusual clinical manifestations, as a definitive diagnosis necessitates a comprehensive evaluation.

Monofluorophore-based Two-Photon Ratiometric Fluorescent Probe for the Quantitative Imaging of Fatty Acid Amide Hydrolase in Live Neurons and Mouse Brain Tissues.

Fatty acid amide hydrolase (FAAH) plays a crucial role in the metabolism of the endocannabinoid system by hydrolyzing a series of bioactive amides, whose abnormal levels are associated with neuronal disorders including Alzheimer's disease (AD). However, due to the lack of suitable quantitative sensing tools, real-time and accurate monitoring of the activity of FAAH in living systems remains unresolved. Herein, a novel enzyme-activated near-infrared two-photon ratiometric fluorescent probe (CANP) based on a naphthylvinylpyridine monofluorophore is successfully developed, in which the electron-withdrawing amide moiety is prone to be hydrolyzed to an electron-donating amine group under the catalysis of FAAH, leading to the activation of the intramolecular charge transfer process and the emergence of a new 80 nm red-shifted emission, thereby achieving a ratiometric luminescence response. Benefiting from the high selectivity, high sensitivity, and ratiometric response to FAAH, the probe CANP is successfully used to quantitatively monitor and image the FAAH levels in living neurons, by which an amyloid ß (Aß)-induced upregulation of endogenous FAAH activity is observed. Similar increases in FAAH activity are found in various brain regions of AD model mice, indicating a potential fatty acid amide metabolite-involved pathway for the pathological deterioration of AD. Moreover, our quantitative FAAH inhibition experiments further demonstrate the great value of CANP as an efficient visual probe for in situ and precise assessment of FAAH inhibitors in complex living systems, assisting the discovery of FAAH-related therapeutic agents.

Nanotechnology-Based Strategy for Enhancing Therapeutic Efficacy in Pancreatic Cancer: Receptor-Targeted Drug Delivery by Somatostatin Analog.

A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes as carriers, an anticancer drug (paclitaxel) as a chemotherapeutic agent, and a modified synthetic somatostatin analog, 5-pentacarbonyl-octreotide, a ligand for somatostatin receptor 2 (SSTR2), as a targeting moiety for pancreatic cancer. The cellular internalization, cytotoxicity, and antitumor activity of the DDS were tested in vitro using human pancreatic ductal adenocarcinoma (PDAC) cells with different expressions of the targeted SSTR2 receptors, and in vivo on immunodeficient mice bearing human PDAC xenografts. The targeted drug delivery system containing paclitaxel exhibited significantly enhanced cytotoxicity compared to non-targeted DDS, and this efficacy was directly related to the levels of SSTR2 expression. It was found that octreotide-targeted DDS proved exceptionally effective in suppressing the growth of PDAC tumors. This study underscores the potential of octreotide-targeted liposomal delivery systems to enhance the therapeutic outcomes for PDAC compared with non-targeted liposomal DDS and Paclitaxel-Cremophor® EL, suggesting a promising avenue for future cancer therapy innovations.