Neutrophil profiling illuminates anti-tumor antigen-presenting potency.

Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.

ST3GAL1 Promotes Malignant Phenotypes in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis, and elucidation of the molecular mechanisms underlying iCCA malignancy is of great significance. Glycosylation, an important post-translational modification, is closely associated with tumor progression. Altered glycosylation, including aberrant sialylation resulting from abnormal expression of sialyltransferases (STs) and neuraminidases (NEUs), is a significant feature of cancer cells. However, there is limited information on the roles of STs and NEUs in iCCA malignancy. Here, utilizing our proteogenomic resources from a cohort of 262 patients with iCCA, we identified ST3GAL1 as a prognostically relevant molecule in iCCA. Moreover, overexpression of ST3GAL1 promoted proliferation, migration, and invasion and inhibited apoptosis of iCCA cells in vitro. Through proteomic analyses, we identified the downstream pathway potentially regulated by ST3GAL1, which was the NF-κB signaling pathway, and further demonstrated that this pathway was positively correlated with malignancy in iCCA cells. Notably, glycoproteomics showed that O-glycosylation was changed in iCCA cells with high ST3GAL1 expression. Importantly, the altered O-glycopeptides underscored the potential utility of O-glycosylation profiling as a discriminatory marker for iCCA cells with ST3GAL1 overexpression. Additionally, miR-320b was identified as a post-transcriptional regulator of ST3GAL1, capable of suppressing ST3GAL1 expression and then reducing the proliferation, migration, and invasion abilities of iCCA cell lines. Taken together, these results suggest ST3GAL1 could serve as a promising therapeutic target for iCCA.

High expression of RTEL1 predicates worse progression in gliomas and promotes tumorigenesis through JNK/ELK1 cascade.

Gliomas are the most common primary intracranial tumor worldwide. The maintenance of telomeres serves as an important biomarker of some subtypes of glioma. In order to investigate the biological role of RTEL1 in glioma. Relative telomere length (RTL) and RTEL1 mRNA was explored and regression analysis was performed to further examine the relationship of the RTL and the expression of RTEL1 with clinicopathological characteristics of glioma patients. We observed that high expression of RTEL1 is positively correlated with telomere length in glioma tissue, and serve as a poor prognostic factor in TERT wild-type patients. Further in vitro studies demonstrate that RTEL1 promoted proliferation, formation, migration and invasion ability of glioma cells. In addition, in vivo studies also revealed the oncogene role of RTEL1 in glioma. Further study using RNA sequence and phospho-specific antibody microarray assays identified JNK/ELK1 signaling was up-regulated by RTEL1 in glioma cells through ROS. In conclusion, our results suggested that RTEL1 promotes glioma tumorigenesis through JNK/ELK1 cascade and indicate that RTEL1 may be a prognostic biomarker in gliomas.

Differentiating calcifications from cerebral microbleeds using quantitative susceptibility mapping.

OBJECTIVES: To differentiate cerebral microbleeds (CMBs) and calcifications using quantitative susceptibility mapping (QSM). METHODS: CMBs were visualized and located using QSM from susceptibility-weighted imaging data collected on a 3-T MR scanner. Calcifications of the pineal gland and the choroid plexus were localized first using CT. All calcifications and CMBs were assessed using QSM to evaluate their magnetic susceptibility. The distribution of the magnetic susceptibility for the CMBs was determined and the CT attenuation was correlated with the mean magnetic susceptibility for the calcifications. RESULTS: A total of 232 hypointense foci were selected from the QSM data: 121 were CMBs and 111 were calcifications. The mean magnetic susceptibility was -214 ± 112 ppb for the calcifications and 392 ± 204 ppb for the CMBs. The minimum value of magnetic susceptibility was 75 ppb for all the CMBs and the maximum value was -52 ppb for all the calcifications. The calcifications were clearly differentiable from the CMBs from the sign alone (p < 0.001). The magnetic susceptibility for the CMBs was 299 ± 133 ppb in the lobar subcortical white matter and 499 ± 220 ppb for deep CMBs in the basal ganglia, thalamus, and brainstem. There was a significant difference in the susceptibility between these two regions (p < 0.001). CONCLUSION: The sign of the magnetic susceptibility was sufficient to differentiate calcifications and CMBs. The concentration of calcium or iron can be determined from the susceptibility value itself. The deep CMBs had higher susceptibility on average than lobar bleeds. CLINICAL RELEVANCE STATEMENT: This study's ability to differentiate between CMBs and calcifications using QSM could enhance diagnostic accuracy, guiding more precise treatment decisions for stroke or tumor patients. KEY POINTS: The sign of magnetic susceptibility is sufficient to differentiate calcifications and CMBs. QSM can successfully differentiate calcifications from microbleeds. The concentration of calcium or iron can be determined from the susceptibility value itself.

Comprehensive characterization of differential glycation in hepatocellular carcinoma using tissue proteomics with stable isotopic labeling.

Glycation is a non-enzymatic posttranslational modification coming from the reaction between reducing sugars and free amino groups in proteins, where early glycation products (fructosyl-lysine, FL) and advanced glycation end products (AGEs) are formed. The occurrence of glycation and accumulation of AGEs have been closely associated with hepatocellular carcinoma (HCC). Here, we reported the characterization of differential glycation in HCC using tissue proteomics with stable isotopic labeling; early glycation-modified peptides were enriched with boronate affinity chromatography (BAC), and AGEs-modified peptides were fractionated with basic reversed-phase separation. By this integrated approach, 3717 and 1137 early and advanced glycated peptides corresponding to 4007 sites on 1484 proteins were identified with a false discovery rate (FDR) of no more than 1%. One hundred fifty-five sites were modified with both early and advanced end glycation products. Five early and 7 advanced glycated peptides were quantified to be differentially expressed in HCC tissues relative to paired adjacent tissues. Most (8 out of 10) of the proteins corresponding to the differential glycated peptides have previously been reported with dysregulation in HCC. The results together may deepen our knowledge of glycation as well as provide insights for therapeutics.

Mid-arm muscle circumference and triceps skinfold thickness associated with cardiometabolic disease in Chinese residents: A prospective cohort study.

BACKGROUND AND AIMS: The association of cardiometabolic disease (CMD) with body muscle and fat mass remains unclear. Mid-arm muscle circumference (MAMC) and triceps skinfold (TSF) thickness are easily obtained measuring methods for these two body compositions. This study aimed to investigate the association of CMD with MAMC and TSF thickness among Chinese residents. METHODS: A total of 9440 eligible participants from the China Health and Nutrition Survey were included in the analysis. Associations of CMD prevalence with MAMC and TSF thickness were estimated using logistic regression models. Multivariable COX proportional-hazards regression models were used to estimate the effect of baseline MAMC and TSF thickness on subsequent CMD. RESULTS: Positive associations of CMD prevalence with MAMC (odds ratio [OR] = 1.169, 95% confidence interval [CI] 1.110-1.232, P < 0.001) and TSF thickness (OR = 1.313, 95%CI 1.240-1.390, P < 0.001) were observed in the cross-sectional analysis. In the longitudinal study, a 1-SD increase in MAMC was associated with a 13.6% increased risk of CMD incidence (hazard ratio [HR] = 1.136, 95%CI 1.073-1.204, P < 0.001), and a 1-SD increase in TSF thickness had a 17.6% increased risk of CMD incidence (HR = 1.176, 95%CI 1.084-1.276, P < 0.001). For the CMD components, both MAMC and TSF thickness contributed to increased incidences of hypertension (HR = 1.163, 95%CI 1.097-1.233, P < 0.001 in MAMC; HR = 1.218, 95%CI 1.110-1.336, P < 0.001 in TSF thickness) and diabetes mellitus (HR = 1.166, 95%CI 1.028-1.323, P = 0.017 in MAMC; HR = 1.352, 95%CI 1.098-1.664, P = 0.004 in TSF thickness). CONCLUSIONS: Individuals with higher MAMC and TSF thickness had an increased incidence of CMD, mainly hypertension and diabetes mellitus. This study revealed a seemingly counterintuitive association between body muscle mass and metabolic homeostasis. Although the potential mechanisms require further exploration, the impact of body muscle mass on metabolic health cannot be ignored.

Measurement of nanocomposite scintillators by terahertz time domain spectroscopy.

Nanocomposite scintillators are expected to combine the advantages of inorganic and plastic scintillators, such as high detection efficiency, high light yield, fast decay time, low cost, and ease of processing. They are currently the forefront and hot field of scintillator research. In this study, a non-destructive method was developed for measuring the content of inorganic components in nanocomposite scintillators by terahertz time-domain spectroscopy. The complex refractive index of B a F 2 nanocomposite scintillators with different mass contents was measured in the terahertz band. As the mass content of B a F 2 nanoparticles increases, the refractive index and extinction coefficient of B a F 2 nanocomposite scintillators also gradually increase in the terahertz band. By combining the effective medium theory, the expected mass content was obtained, proving the feasibility of this measuring method.

Effect of WeChat-Based Medication Guidance on Symptoms and Serological Parameters in Children with Mycoplasma Pneumoniae.

Objective: The aim of this study was to assess the effect of microsoft-based medication guidance on the level of symptoms and serological indicators in children receiving budesonide nebulisation combined with terbutaline for the treatment of Mycoplasma pneumoniae pneumoniae (MPP). Methods: A total of 109 children with MPP treated in The First Affiliated Hospital of Ningbo University of China between October 2022 and April 2023 were divided into the conventional group (n=54, with medication guidance by telephone follow-up) and the WeChat group (n=55, with medication guidance based on the WeChat platform) using a randomized number table. The time to resolution of symptoms, serological index levels, incidence of adverse drug events, medication adherence scores and satisfaction rate of family guidance were compared between the two groups. Results: The disappearance time of symptoms such as wheezing and cough in the WeChat group was shorter than that in the conventional group (P < .05). After treatment, the C-reactive protein (CRP), interleukin-6 (IL-6) and calcitoninogen (PCT) levels and the incidence of adverse drug events were lower in the WeChat group than in the conventional group (P < .05). After treatment, the levels of forceful spirometry (FVC), 1st-second expiratory volume (FEV1), peak expiratory flow rate (PEF), medication compliance score and family guidance satisfaction rate were higher in the WeChat group than in the conventional group (P < .05). Conclusion: WeChat-based medication guidance can optimize the therapeutic effect of MPP, improve children's medication compliance and satisfaction rate of family guidance, and reduce the occurrence of adverse drug events.

Au/PANI@PtCu-based electrochemical immunosensor for ultrasensitive determination of pro-gastrin-releasing peptide.

An ultrasensitive sandwich-type electrochemical immunosensor for pro-gastrin-releasing peptide (ProGRP) detection was constructed based on PtCu nanodendrites functionalized Au/polyaniline nanospheres (Au/PANI@PtCu). The prepared Au/PANI@PtCu nanocomposites not only possessed excellent electro-catalytic activity of H2O2 reduction due to the synergistic effect between the Au/PANI and PtCu NDs but also provided large specific surface area for detection of antibodies (Ab2) immobilization. In addition, Au nanoparticles encapsulated multi-wall carbon nanotubes (AuNPs@MWCNTs) were also applied to modify the glassy carbon electrode interface for loading numerous capture antibodies (Ab1). In the presence of target ProGRP, a sandwich-type electrochemical immunosensor showed a strong current response from the electro-catalysis of Au/PANI@PtCu toward H2O2 reduction. Benefiting from the exceptional electro-catalytic performance of Au/PANI@PtCu and the high conductivity of AuNPs@MWCNTs, the sandwich-type immunoassay exhibited remarkable sensitivity in detection. The linear range extended from 100 fg/mL to 10 ng/mL, while achieving an impressively low limit of detection of 77.62 fg/mL.

Graphene Nanoplatelets/Polydimethylsiloxane Flexible Strain Sensor with Improved Sandwich Structure.

In engineering measurements, metal foil strain gauges suffer from a limited range and low sensitivity, necessitating the development of flexible sensors to fill the gap. This paper presents a flexible, high-performance piezoresistive sensor using a composite consisting of graphene nanoplatelets (GNPs) and polydimethylsiloxane (PDMS). The proposed sensor demonstrated a significantly wider range (97%) and higher gauge factor (GF) (6.3), effectively addressing the shortcomings of traditional strain gauges. The microstructure of the GNPs/PDMS composite was observed using a scanning electron microscope, and the distribution of the conductive network was analyzed. The mechanical behavior of the sensor encapsulation was analyzed, leading to the determination of the mechanisms influencing encapsulation. Experiments based on a standard equal-strength beam were conducted to investigate the influence of the base and coating dimensions of the sensor. The results indicated that reducing the base thickness and increasing the coating length both contributed to the enhancement of the sensor's performance. These findings provide valuable guidance for future development and design of flexible sensors.

Flexible Graphene Film-Based Antenna Sensor for Large Strain Monitoring of Steel Structures.

In the field of wireless strain monitoring, it is difficult for the traditional metal-made antenna sensor to conform well with steel structures and monitor large strain deformation. To solve this problem, this study proposes a flexible antenna strain sensor based on a ductile graphene film, which features a 6.7% elongation at break and flexibility due to the microscopic wrinkle structure and layered stacking structure of the graphene film. Because of the use of eccentric embedding in the feeding form, the sensor can be miniaturized and can simultaneously monitor strain in two directions. The sensing mechanism of the antenna is analyzed using a void model, and an antenna is designed based on operating frequencies of 3 GHz and 3.5 GHz. The embedding size is optimized using a Smith chart and impedance matching principle. Both the simulation and experimental results verify that the resonant frequency and strain magnitude are linearly inversely proportional. The experimental results show that the strain sensitivity is 1.752 kHz/µÎµ along the geometric length and 1.780 kHz/µÎµ along the width, with correlation coefficients of 0.99173 and 0.99295, respectively.

Rare case of spontaneous duodeno-colic fistula.

A 48-year-old woman presented to the outpatient clinic with a 4-month history of alternating diarrhea and constipation with bloating. Physical examination revealed a body mass index of 22.89 kg/m², normal development, and no tenderness or rebound tenderness in the abdomen. The patient has maintained a stable body size since birth, with a previously healthy status and no history of abdominal surgery or trauma. Endoscopic examination revealed an abnormal channel between the posterior wall of the duodenal bulb to the hepatic flexure of the colon. The patient was managed with conservative treatment, including acid suppression and modulation of the gut microbiota, and was closely monitored. Surgical intervention would only be considered in the event of severe symptoms or complications. Over a five-month follow-up period, the patient's symptoms improved.

Radical-Based Enantioconvergent Reductive Couplings of Racemic Allenes and Aldehydes.

Transition metal-catalyzed radical-based enantioconvergent reactions have become a powerful strategy to synthesize enantiopure compounds from racemic starting materials. However, existing methods primarily address precursors with central chirality, neglecting those with axial chirality. Herein, we describe the enantioconvergent reductive coupling of racemic allenes with aldehydes, facilitated by a photoredox, chromium, and cobalt triple catalysis system. This method selectively affords one product from sixteen possible regio- and stereoisomers. The protocol leverages CoIII-H mediated hydrogen atom transfer (MHAT) and Cr-catalyzed radical-polar crossover for efficient stereoablation of axial chirality and asymmetric addition, respectively. Supported by mechanistic insights from control experiments, deuterium labeling, and DFT calculations, our approach offers synthetic chemists a valuable tool for creating enantioenriched chiral homoallylic alcohols, promising to advance radical-based strategies for synthesizing complex chiral molecules.

Guest-Regulated Generation of Reactive Oxygen Species from Porphyrin-Based Multicomponent Metallacages for Selective Photocatalysis.

The development of novel materials for highly efficient and selective photocatalysis is crucial for their practical applications. Herein, we employ the host-guest chemistry of porphyrin-based metallacages to regulate the generation of reactive oxygen species and further use them for the selective photocatalytic oxidation of benzyl alcohols. Upon irradiation, the sole metallacage (6) can generate singlet oxygen (1O2) effectively via excited energy transfer, while its complex with C70 (6⊃C70) opens a pathway for electron transfer to promote the formation of superoxide anion (O2⋅-), producing both 1O2 and O2⋅-. The addition of 4,4'-bipyridine (BPY) to complex 6⊃C70 forms a more stable complex (6⊃BPY) via the coordination of the Zn-porphyrin faces of 6 and BPY, which drives fullerenes out of the cavities and restores the ability of 1O2 generation. Therefore, benzyl alcohols are oxidized into benzyl aldehydes upon irradiation in the presence of 6 or 6⊃BPY, while they are oxidized into benzoic acids when 6⊃C70 is employed as the photosensitizing agent. This study demonstrates a highly efficient strategy that utilizes the host-guest chemistry of metallacages to regulate the generation of reactive oxygen species for selective photooxidation reactions, which could promote the utilization of metallacages and their related host-guest complexes for photocatalytic applications.

Integration of Perylene Diimide into a Covalent Organic Framework for Photocatalytic Oxidation.

Perylene diimides (PDIs) have garnered considerable attention due to its immense potential in photocatalysis. However, manipulating the molecular packing within their aggregates and enhancing the efficiency of photogenerated carrier recombination remain significant challenges. In this study, we demonstrate the incorporation of a PDI unit into a covalent organic framework (COF), named PDI-PDA, by linking an ortho-substituted PDI with p-phenylenediamine (PDA) to control its intermolecular aggregation. The incorporation enables precise modulation of electron transfer dynamics, leading to a ten-fold increase in the efficiency of photocatalytic oxidation of thioether to sulfoxide with PDI-PDA compared to the PDI molecular counterpart, achieving yields exceeding 90%. Electron property studies and density functional theory calculations show that the PDI-PDA with its well-defined crystal structure, enhances π-π stacking and lowers the electron transition barrier. Moreover, the strong electron-withdrawing ability of the PDI unit promotes the spatial separation of the valency band maximum and conduction band minimum of PDI-PDA suppressing the rapid recombination of photogenerated electron-hole pairs and improving charge separation efficiency to give high photocatalytic efficiency. This study provides a brief yet effective way for the improvement of the photocatalytic efficiency of commonly used PDI-based dyes by integrating them into a framework skeleton.

End-extended Conjugation Strategy to Reduce the Efficiency-Stability-Mechanical Robustness Gap in Binary All-Polymer Solar Cells.

Concurrently achieving high efficiency, mechanical robustness and thermal stability is critical for the commercialization of all-polymer solar cells (APSCs). However, APSCs usually demonstrate complicated morphology, primarily attributed to the polymer chain entanglement which has a detrimental effect on their fill factors (FF) and morphology stability. To address these concerns, an end-group extended polymer acceptor, PY-NFT, was synthesized and studied. The morphology analysis showed a tightly ordered molecular packing mode and a favorable phase separation was formed. The PM6:PY-NFT-based device achieved an exceptional PCE of 19.12% (certified as 18.45%), outperforming the control PM6:PY-FT devices (17.14%). This significant improvement highlights the record-high PCE for binary APSCs. The thermal aging study revealed that the PM6:PY-NFT blend exhibited excellent morphological stability, thereby achieving superior device stability, retaining 90% of initial efficiency after enduring thermal stress (65 °C) for 1500 hours. More importantly, the PM6:PY-NFT blend film exhibited outstanding mechanical ductility with a crack onset strain of 24.1%. Overall, rational chemical structure innovation, especially the conjugation extension strategy to trigger appropriate phase separation and stable morphology, is the key to achieving high efficiency, improved thermal stability and robust mechanical stability of APSCs.

Dynamic Kinetic Reductive Conjugate Addition for Construction of Axial Chirality Enabled by Synergistic Photoredox/Cobalt Catalysis.

Conjugate addition is among the most important synthetic protocols for constructing carbon skeletons and is widely used to synthesize natural products and drugs. However, asymmetric catalysis studies have mainly focused on constructing stereogenic centers arising from conjugate alkenes. Here, we report the first photoinduced cobalt-catalyzed dynamic kinetic reductive conjugate addition reaction that enables the formation of heterobiaryls with axial chirality (45 examples, up to 91% yield and 97% ee). This method features mild reaction conditions, good functional-group tolerance, and excellent enantiomeric control. Significantly, large amounts of metal waste and precious metal catalysts can be avoided under these conditions. Migration of the chiral arylcobalt species into the alkene might be the rate-determining step based on kinetic studies.

Glycoproteomic contributions to hepatocellular carcinoma research: a 2023 update.

INTRODUCTION: Hepatocellular carcinoma (HCC) represents a significant burden globally, which ranks sixth among the most frequently diagnosed cancers and stands as the third leading cause of cancer-related mortality. Glycoproteomics, as an important branch of proteomics, has already made significant achievements in the field of HCC research. Aberrant protein glycosylation has shown to promote the malignant transformation of hepatocytes by modulating a wide range of tumor-promoting signaling pathways. The glycoproteome provides valuable information for understanding cancer progression, tumor immunity, and clinical outcome, which could serve as potential diagnostic, prognostic, and therapeutic tools in HCC. AREAS COVERED: In this review, recent advances of glycoproteomics contribute to clinical applications (diagnosis and prognosis) and molecular mechanisms (hepatocarcinogenesis, progression, stemness and recurrence, and drug resistance) of HCC are summarized. EXPERT OPINION: Glycoproteomics shows promise in HCC, enhancing early detection, risk stratification, and personalized treatments. Challenges include sample heterogeneity, diverse glycans structures, sensitivity issues, complex workflows, limited databases, and incomplete understanding of immune cell glycosylation. Addressing these limitations requires collaborative efforts, technological advancements, standardization, and validation studies. Future research should focus on targeting abnormal protein glycosylation therapeutically. Advancements in glycobiomarkers and glycosylation-targeted therapies will greatly impact HCC diagnosis, prognosis, and treatment.

Measurement of Hyperfine Structure and the Zemach Radius in

We investigate the 2^{3}S_{1}-2^{3}P_{J} (J=0, 1, 2) transitions in ^{6}Li^{+} using the optical Ramsey technique and achieve the most precise values of the hyperfine splittings of the 2^{3}S_{1} and 2^{3}P_{J} states, with smallest uncertainty of about 10 kHz. The present results reduce the uncertainties of previous experiments by a factor of 5 for the 2^{3}S_{1} state and a factor of 50 for the 2^{3}P_{J} states, and are in better agreement with theoretical values. Combining our measured hyperfine intervals of the 2^{3}S_{1} state with the latest quantum electrodynamic (QED) calculations, the improved Zemach radius of the ^{6}Li nucleus is determined to be 2.44(2) fm, with the uncertainty entirely due to the uncalculated QED effects of order mα^{7}. The result is in sharp disagreement with the value 3.71(16) fm determined from simple models of the nuclear charge and magnetization distribution. We call for a more definitive nuclear physics value of the ^{6}Li Zemach radius.

Aminoguanidine-Catalyzed Reductive Cyclization of o-Phenylenediamines with CO2 in the Presence of Triethoxysilane.

An inexpensive and efficient aminoguanidine-catalyzed reductive cyclization of o-phenylenediamines with CO2 in the presence of triethoxysilane is described. Various functionalized benzimidazoles, benzoxazole, and benzothiazole were synthesized in high yields. Mechanistic studies indicate that formic acid as a cocatalyst promotes the cyclization reaction.