A Zn-MOF-GOx-based Cascade Nanoreactor Promotes Diabetic Infected Wound Healing by NO Release and Microenvironment Regulation.

Diabetic wound healing is a great clinical challenge due to the microenvironment of hyperglycemia and high pH value, bacterial infection and persistent inflammation. Here, we develop a cascade nanoreactor hydrogel (Arg@Zn-MOF-GOx Gel, AZG-Gel) with arginine (Arg) loaded Zinc metal organic framework (Zn-MOF) and glucose oxidase (GOx) based on chondroitin sulfate (CS) and Pluronic (F127) to accelerate diabetic infected wound healing. GOx in AZG-Gel was triggered by hyperglycemic environment to reduce local glucose and pH, and simultaneously produced hydrogen peroxide (H2O2) to enable Arg to release nitric oxide (NO) for inflammation regulation, providing a suitable microenvironment for wound healing. Zinc ions (Zn2+) released from acid-responsive Zn-MOF significantly inhibited the proliferation and biofilm formation of S.aureus and E.coli. AZG-Gel significantly accelerated diabetic infected wound healing by down-regulating pro-inflammatory tumor necrosis factor (TNF)-α and interleukin (IL)-6, up-regulating anti-inflammatory factor IL-4, promoting angiogenesis and collagen deposition in vivo. Collectively, our nanoreactor cascade strategy combining "endogenous improvement (reducing glucose and pH)" with "exogenous resistance (anti-bacterial and anti-inflammatory)" provides a new idea for promoting diabetic infected wound healing by addressing both symptoms and root causes. STATEMENT OF SIGNIFICANCE: A cascade nanoreactor (AZG-Gel) is constructed to solve three key problems in diabetic wound healing, namely, hyperglycemia and high pH microenvironment, bacterial infection and persistent inflammation. Local glucose and pH levels are reduced by GOx to provide a suitable microenvironment for wound healing. The release of Zn2+ significantly inhibits bacterial proliferation and biofilm formation, and NO reduces wound inflammation and promotes angiogenesis. The pH change when AZG-Gel is applied to wounds is expected to enable the visualization of wound healing to guide the treatment of diabetic wound. Our strategy of "endogenous improvement (reducing glucose and pH)" combined with "exogenous resistance (anti-bacterial and anti-inflammatory)" provides a new way for promoting diabetic wound healing.

Early GnRH-agonist therapy does not negatively impact the endometrial repair process or live birth rate.

Study objective: To investigate whether different timings of GnRH-a downregulation affected assisted reproductive outcomes in infertile women with moderate-to-severe intrauterine adhesions (IUAs) accompanied by adenomyosis. Design: A retrospective case series. Setting: An assisted reproductive technology center. Patients: The study reviewed 123 infertile women with moderate-to-severe IUAs accompanied by adenomyosis undergoing their first frozen-thawed embryo transfer (FET) cycles between January 2019 and December 2021. Measurements and main results: The majority of patients had moderate IUA (n=116, 94.31%). The average Basal uterine volume was 73.58 ± 36.50 cm3. The mean interval from operation to the first downregulation was 21.07 ± 18.02 days (range, 1-79 days). The mean duration of hormone replacement therapy (HRT) was 16.93 ± 6.29 days. The average endometrial thickness on the day before transfer was 10.83 ± 1.75 mm. A total of 70 women achieved clinical pregnancy (56.91%). Perinatal outcomes included live birth (n=47, 67.14%), early miscarriage (n=18, 25.71%), and late miscarriage (n=5, 7.14%). The time interval between uterine operation and the first downregulation was not a significant variable affecting live birth. Maternal age was the only risk factor associated with live birth (OR:0.89; 95% CI: 0.79-0.99, P=0.041). Conclusions: The earlier initiation of GnRH-a to suppress adenomyosis prior to endometrial preparation for frozen embryo transfer did not negatively impact repair of the endometrium after resection.

Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality.

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

The Analysis of Leontopodium leontopodioides (Willd.) Beauv. Chemical Composition by GC/MS and UPLC-Q-Orbitrap MS.

Leontopodium leontopodioides (Willd.) Beauv. (L. leontopodioides.) has been used to treat lung diseases in traditional Chinese medicine (TCM). However, a systematic analysis of its chemical components has not been reported so far. In this study, UPLC-Q-Orbitrap MS and GC-MS were applied to investigate the chemical composition of the water extracts and essential oils of L. leontopodioides. UPLC-Q-Orbitrap MS adopts a heating electrospray ionization source, collecting primary and secondary mass spectrometry data in positive and negative ions, respectively, and uses Compound Discoverer 3.2 software to analyze the collected raw data. As a result, a total of 39 compounds were identified from their high-resolution mass spectra in both positive and negative ionization modes, including 13 flavonoids and their glycosides, 15 phenolic acids, 4 oligosaccharides and glycosides, 4 pentacyclic triterpenoids, and 3 other compounds. Among them, 18 chemical components have not been reported in L. leontopodioides. In the GC-MS section, two common organic solvents (n-hexane and diethyl ether) were used to extract essential oils, and the mass spectra were recorded at 70 eV (electron impact) and scanned in the range of 35∼450 m/z. Compounds were identified using NIST (version 2017), and the peak area normalization method was used to calculate their relative amounts. Finally, 17 components were identified in the volatile oil extracted with n-hexane, accounting for 80.38% of the total volatile oil, including monoterpenoids, phenylpropene, fatty acids, and aliphatic hydrocarbons. In the volatile oil extracted with diethyl ether, 16 components were identified, accounting for 73.50% of the total volatile oil, including phenylpropene, aliphatic hydrocarbons, monoterpenoids, fatty acids, and esters. This study was the first to conduct a comprehensive analysis of the chemical composition of the L. leontopodioides water extract and its essential oil, and a comprehensive chemical composition spectrum was constructed, to lay a foundation for its further pharmacodynamic material basis and quality evaluation.

Aspleniumguodanum (Aspleniaceae), a distinct new fern species from northern Guangdong, China, based on morphological data and molecular phylogeny.

A new spleenwort species, Aspleniumguodanum, was found and described from Danxia landform region in Guangdong, China. The new species has close resemblance to A.subcrenatum Ching ex S.H.Wu in morphology, but can be distinguished by having plants small, stipes and rachises not covered with fibrous scales, relatively fewer pairs of pinnae, pinnae short, pinna margin weakly biserrate, pinna apex acute and lower pinnae obviously reduced. Phylogenetic analyses, based on six plastid markers (atpB, rbcL, rps4 & rps4-trnS and trnL & trnL-F) of the new species and its relatives, support a close relationship between A.guodanum and A.subcrenatum. Only one population with no more than 50 individuals were found and, therefore, it is recommended to be classified as Critically Endangered (CR) following IUCN Red List Criteria.

Ultralow-power optoelectronic synaptic transistors based on polyzwitterion dielectrics for in-sensor reservoir computing.

Bio-inspired transistor synapses use solid electrolytes to achieve low-power operation and rich synaptic behaviors via ion diffusion and trapping. While these neuromorphic devices hold great promise, they still suffer from challenges such as high leakage currents and power consumption, electrolysis risk, and irreversible conductance changes due to long-range ion migrations and permanent ion trapping. In addition, their response to light is generally limited because of "exciton-polaron quenching", which restricts their potential in in-sensor neuromorphic visions. To address these issues, we propose replacing solid electrolytes with polyzwitterions, where the cation and anion are covalently concatenated via a flexible alkyl chain, thus preventing long-range ion migrations while inducing good photoresponses to the transistors via interfacial charge trapping. Our detailed studies reveal that polyzwitterion-based transistors exhibit optoelectronic synaptic behavior with ultralow-power consumption (~250 aJ per spike) and enable high-performance in-sensor reservoir computing, achieving 95.56% accuracy in perceiving the trajectory of moving basketballs.

[Application of microwave vacuum drying with process management in extract drying of personalized traditional Chinese medicine preparations].

Extracts are important intermediates in the production of traditional Chinese medicines preparations. The drying effect of extracts will directly affect the subsequent production process and the quality of the preparation. To meet the requirements of high drug loading, short time consumption, and simple production process of personalized traditional Chinese medicine preparations, this study explored the application of multi-program microwave vacuum drying process in the extract drying of personalized traditional Chinese medicine preparations. The influencing factors of microwave vacuum drying process were investigated for 5 excipients and 40 prescriptions. Taking the feasibility of drying, drying rate, drying time, and dried extract status as indicators, this study investigated the feeding requirements of microwave vacuum drying. With the dried extract status as the evaluation indicator, the three drying programs(A, B, and C) were compared to obtain the optimal drying condition. The experimental results showed that the optimal feeding conditions for microwave vacuum drying were material layer thickness of 2 cm and C program(a total of 7 drying processes), which solved the problem of easy scorching in microwave drying with process management. Furthermore, the preset moisture content of the dried extract in microwave drying should be 4%-5%, so that the dried extract of traditional Chinese medicine preparation had uniform quality, complete drying, and no scorching. This study lays a foundation for the application of microwave drying in the production of traditional Chinese medicine preparations, promoting the high-quality development of personalized traditional Chinese medicine preparations.

Prognostic value of pre-treatment [18F] FDG PET/CT in recurrent nasopharyngeal carcinoma without distant metastasis.

BACKGROUND: [18 F]-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has the ability to detect local and/or regional recurrence as well as distant metastasis. We aimed to evaluate the prognosis value of PET/CT in locoregional recurrent nasopharyngeal (lrNPC). METHODS: A total of 451 eligible patients diagnosed with recurrent I-IVA (rI-IVA) NPC between April 2009 and December 2015 were retrospectively included in this study. The differences in overall survival (OS) of lrNPC patients with and without PET/CT were compared in the I-II, III-IVA, r0-II, and rIII-IVA cohorts, which were grouped by initial staging and recurrent staging (according to MRI). RESULTS: In the III-IVA and rIII-IVA NPC patients, with PET/CT exhibited significantly higher OS rates in the univariate analysis (P = 0.045; P = 0.009; respectively). Multivariate analysis revealed that with PET/CT was an independent predictor of OS in the rIII-IVA cohort (hazard ratio [HR] = 0.476; 95% confidence interval [CI]: 0.267 to 0.847; P = 0.012). In the rIII-IVA NPC, patients receiving PET/CT sacns before salvage surgery had a better prognosis compared with MRI alone (P = 0.036). The recurrent stage (based on PET/CT) was an independent predictor of OS. (r0-II versus [vs]. rIII-IVA; HR = 0.376; 95% CI: 0.150 to 0.938; P = 0.036). CONCLUSION: The present study showed that with PET/CT could improve overall survival for rIII-IVA NPC patients. PET/CT appears to be an effective method for assessing rTNM staging.

Effects of different exercise interventions on chemotherapy-related cognitive impairment in patients with breast cancer: a study protocol for systematic review and network meta-analysis.

INTRODUCTION: Breast cancer stands as the most prevalent type of cancer affecting women globally, and chemotherapy plays a pivotal role in its treatment by diminishing tumour recurrence and enhancing the survival rates of patients. However, chemotherapy-related cognitive impairment (CRCI) often occurs in patients undergoing treatment. Although multiple clinical trials have indicated that exercise therapy can improve CRCI in patients with breast cancer, there are variations in the types of exercise interventions and their effectiveness. We aim to perform a pioneering network meta-analysis (NMA) to assess and prioritise the effectiveness of various exercise interventions in enhancing cognitive function in patients with breast cancer undergoing chemotherapy. METHODS AND ANALYSIS: We will search multiple databases, including PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang and Sinomed databases, from their inception to May 2023. The main outcome is the cognitive function changes in patients with breast cancer, including subjective and objective results. We will specifically include randomised controlled trials reported in English and Chinese languages, whose primary outcome consists of an assessment of the cognitive function of patients with breast cancer using standardised and validated assessment tools, encompassing both subjective and objective outcomes. The quality of all the trials included will be evaluated based on 'Version 2 of the Cochrane tool for assessing the risk of bias in randomized controlled trials (RoB2)'. We will conduct a Bayesian NMA to thoroughly evaluate and compare the effectiveness of different exercise interventions. We will use cumulative ranking probability plots to estimate the ranking of the best interventions for various exercises. Network plots and funnel plots will be employed to display the study sizes and participants of each exercise intervention, as well as potential publication biases. ETHICS AND DISSEMINATION: The study findings will be shared via peer-reviewed journals to ensure the highest quality and credibility of the research. As the reporting will not include any private patient data, there are no ethical considerations associated with this protocol. PROSPERO REGISTRATION NUMBER: CRD42023406597.

RER-YOLO: improved method for surface defect detection of aluminum ingot alloy based on YOLOv5.

Aluminum ingot alloy is one of the commonly used materials in industrial production and intelligent manufacturing, whose quality directly affects the performance of aluminum processed products. Therefore, the inspection of surface defects of aluminum ingot alloy is extremely valuable for actual industrial engineering. Aiming at the issues of low detecting precision and the slowly processing rate thatexisted in the traditional target detection methods for aluminum ingot alloy dataset, the YOLOv5-based improvement model RER-YOLO is proposed. Firstly, the aluminum ingot alloy dataset is coped with the image pretreatment methods of rotation, translation, contrast and brightness transformations in a random combination so as to boost the capacity of generalization for model training. Secondly, a multi-scale characteristic extraction network block (Res2Net) is utilized to take the place of the C3 block in the previous YOLOv5 to augment the model's ability that can accurately extract rich features. Finally, an over-parameterization-based re-parameterized convolutional block is utilized in place of the 3×3 convolutional blocks in the Res2Net residual block and baseline model, enlarging the search space of the network and boosting the model's fitting ability while maintaining inference rate. The comparison experimental results demonstrate that the RER-YOLO reaches a mean average precision of 75.1% on the aluminum ingot alloy dataset, which is higher 4.9% than the conventional YOLOv5 and does not increase the inference delay. It also improves the detection accuracy by 12.7% for burr defects, which are fewer in number in the dataset and the defect features are difficult to extract. It can be seen that the presented model in this study has an important reference value towards detecting surface defects in aluminum ingot alloy.

Early administration of Wumei Wan inhibit myeloid-derived suppressor cells via PI3K/Akt pathway and amino acids metabolism to prevent Colitis-associated Colorectal Cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC. AIM OF THE STUDY: The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC. MATERIALS AND METHODS: Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by UHPLCQTOF/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and western blot to explore the key pathway of WMW in preventing CAC. RESULTS: WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1ß, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4+ T cells and CD8+ T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM+DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM+DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC. CONCLUSION: WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM+DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs.

Prostate cancer-associated transcript 6 (PCAT6) promotes epithelial-mesenchymal transition and stemness and worsens prognosis in patients with colorectal cancer.

Approximately 20% of colorectal cancer (CRC) patients are first diagnosed with metastatic colorectal cancer (mCRC) because they develop symptoms at an advanced stage. Despite advancements in treatment, patients with metastatic disease still experience inferior survival rates. Our objective is to investigate the association between long noncoding RNAs (lncRNAs) and prognosis and to explore their role in mCRC. In this study, we find that elevated expression of PCAT6 is independently linked to unfavourable survival outcomes in The Cancer Genome Atlas (TCGA) data, and this finding is further confirmed in CRC samples obtained from Fudan University Shanghai Cancer Center. Cell lines and xenograft mouse models are used to examine the impact of PCAT6 on tumor metastasis. Knockdown of PCAT6 is observed to impede the metastatic phenotype of CRC, as evidenced by functional assays, demonstrating the suppression of epithelial-mesenchymal transition (EMT) and stemness. Our findings show the significance of PCAT6 in mCRC and its potential use as a prognostic biomarker.

Synthesis of Spiro Polycyclic N-Heterocycles and Indolecarbazoles via Merging Oxidative Coupling and Cascade Palladium-Catalyzed Intramolecular Oxidative Cyclization.

We report a step-economic strategy for the direct synthesis of spiro polycyclic N-heterocycles and indolecarbazole-fused naphthoquinones by merging oxidative coupling and cascade palladium-catalyzed intramolecular oxidative cyclization. In the protocol, bi-indolylnaphthoquinones were first synthesized by oxidative coupling of indoles and naphthoquinones. Subsequent cascade palladium-catalyzed intramolecular oxidative cyclization of bi-indolylnaphthoquinones gave spiro polycyclic N-heterocycles and indolecarbazoles. The intramolecular oxidative cyclization approach could also be realized by the presence or absence of iron catalysts under standard conditions. This protocol is featured with moderate to excellent yields, a wide substrate scope, and divergent structures of products.

Solution-processable low-voltage carbon nanotube field-effect transistors with high-krelaxor ferroelectric polymer gate insulator.

Achieving energy-efficient and high-performance field-effect transistors (FETs) is one of the most important goals for future electronic devices. This paper reports semiconducting single-walled carbon nanotube FETs (s-SWNT-FETs) with an optimized high-krelaxor ferroelectric insulator P(VDF-TrFE-CFE) thickness for low-voltage operation. The s-SWNT-FETs with an optimized thickness (∼800 nm) of the high-kinsulator exhibited the highest average mobility of 14.4 cm2V-1s-1at the drain voltage (ID) of 1 V, with a high current on/off ratio (Ion/off>105). The optimized device performance resulted from the suppressed gate leakage current (IG) and a sufficiently large capacitance (>50 nF cm-2) of the insulating layer. Despite the extremely high capacitance (>100 nF cm-2) of the insulating layer, an insufficient thickness (<450 nm) induces a highIG, leading to reducedIDand mobility of s-SWNT-FETs. Conversely, an overly thick insulator (>1200 nm) cannot introduce sufficient capacitance, resulting in limited device performance. The large capacitance and sufficient breakdown voltage of the insulating layer with an appropriate thickness significantly improved p-type performance. However, a reduced n-type performance was observed owing to the increased electron trap density caused by fluorine proportional to the insulator thickness. Hence, precise control of the insulator thickness is crucial for achieving low-voltage operation with enhanced s-SWNT-FET performance.

A review of disease risk prediction methods and applications in the omics era.

Risk prediction and disease prevention are the innovative care challenges of the 21st century. Apart from freeing the individual from the pain of disease, it will lead to low medical costs for society. Until very recently, risk assessments have ushered in a new era with the emergence of omics technologies, including genomics, transcriptomics, epigenomics, proteomics, and so on, which potentially advance the ability of biomarkers to aid prediction models. While risk prediction has achieved great success, there are still some challenges and limitations. We reviewed the general process of omics-based disease risk model construction and the applications in four typical diseases. Meanwhile, we highlighted the problems in current studies and explored the potential opportunities and challenges for future clinical practice.

Orientation of graphene nanosheets in suspension under an electric field: theoretical model and molecular dynamic simulations.

Orientation regulation of nanoparticles in a suspension by an electric field is a powerful tool to tune its mechanical, thermal, optical, electrical properties etc. However, how molecular modification can affect the orientation of two-dimensional nanoparticles is still unclear. In this paper, the influence of molecular modification on the orientation of graphene nanosheets (GNS) in water was investigated through theoretical analyses and molecular dynamics (MD) simulations. Firstly, a new orientation angle model was proposed, which considers hydration effects, dipole moments and resistance torque. Then, MD simulations were conducted to investigate the effects of position, direction, type, and number of functional groups on the orientation of GNS. The trend observed in MD simulations is consistent with the proposed theoretical model. The results reveal that, under the combined influence of the dipole moment and hydration effects, the modification with hydrophilic functional groups can reduce the orientation angle from 21.31° to 8.34°, while the modification with hydrophobic functional groups increases it to 26.43°. Among the hydrophilic functional groups, orientation of hydroxylated GNS is the best. With an increase in the number of hydroxyl groups, orientation angle is decreased from 12.61° to 8.34°. This work can provide valuable guidance for the design of high-performance suspensions and composites, such as thermal smart materials with adjustable thermal conductivity and intelligent devices with tailored capabilities.

Claudin18.2 expression and its clinicopathological feature in adenocarcinoma from various parts.

AIMS: To clarify claudin18.2 expression and its clinicopathological features in various cancers, especially in lung adenocarcinoma. METHODS: Immunohistochemistry staining and fluorescence in situ hybridisation (FISH) were performed to detect claudin18.2 expression and CLDN18 gene rearrangement in adenocarcinoma from different organs. RESULTS: The results showed that claudin18.2 expression was found in 68% (27 of 40) of lung mucinous adenocarcinoma, 52% (16 of 31) of cholangiocarcinoma, 2% (10 of 423) of colorectal adenocarcinoma tissue microarray, 27% (6 of 22) of colorectal mucinous adenocarcinoma and 30% (3 of 10) of cervical adenocarcinoma, but not in all 39 cases of invasive breast adenocarcinoma by immunohistochemistry staining. There was significantly positive correlation between ratio of claudin18.2-positive carcinoma cells and staining intensity in lung mucinous adenocarcinoma and cholangiocarcinoma. Claudin18.2 expression was much more in female patients than male patients with lung mucinous adenocarcinoma. In addition, cholangiocarcinoma with claudin18.2 expression was more aggressive and had perineural invasion. Intraductal papillary neoplasm of the bile duct and epithelial dysplasia of the adjacent bile in cholangiocarcinoma also showed claudin18.2 expression. All three cases of cervical adenocarcinoma with claudin18.2 expression were moderately differentiated adenocarcinoma including one human papillomavirus (HPV)-associated carcinoma, two non-HPV-associated and gastric-type carcinoma. CLDN18 gene rearrangement was not found in all 22 cases with high claudin18.2 expression by FISH. CONCLUSIONS: Our results suggest claudin18.2 might be a potential biomarker for targeted therapy on lung mucinous adenocarcinoma, cholangiocarcinoma, colorectal mucinous adenocarcinoma and gastric-type cervical adenocarcinoma.

Pd NP-loaded covalent organic framework for pH-switched Pickering emulsion catalytic dechlorination.

Quinoline carboxylic acid-linked and Pd nanoparticle (NP)-loaded COF nanospheres were constructed via a three-component one-pot Doebner reaction and post-synthetic metalation. The obtained Pd@DhaTAPB-COOH solid stabilizer can greatly promote the pH-switched recyclable Pickering interfacial dechlorination reaction, which sheds light on the bright future of smart Pickering emulsion catalysis.

Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns.

Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.