Ultrasonic-assisted Fenton reaction inducing surface reconstruction endows nickel/iron-layered double hydroxide with efficient water and organics electrooxidation.

Nickel/iron-layered double hydroxide (NiFe-LDH) tends to undergo an electrochemically induced surface reconstruction during the water oxidation in alkaline, which will consume excess electric energy to overcome the reconstruction thermodynamic barrier. In the present work, a novel ultrasonic wave-assisted Fenton reaction strategy is employed to synthesize the surface reconstructed NiFe-LDH nanosheets cultivated directly on Ni foam (NiFe-LDH/NF-W). Morphological and structural characterizations reveal that the low-spin states of Ni2+ (t2g6eg2) and Fe2+ (t2g4eg2) on the NiFe-LDH surface partially transform into high-spin states of Ni3+ (t2g6eg1) and Fe3+ (t2g3eg2) and formation of the highly active species of NiFeOOH. A lower surface reconstruction thermodynamic barrier advantages the electrochemical process and enables the NiFe-LDH/NF-W electrode to exhibit superior electrocatalytic water oxidation activity, which delivers 10 mA cm-2 merely needing an overpotential of 235 mV. Besides, surface reconstruction endows NiFe-LDH/NF-W with outstanding electrooxidation activities for organic molecules of methanol, ethanol, glycerol, ethylene glycol, glucose, and urea. Ultrasonic-assisted Fenton reaction inducing surface reconstruction strategy will further advance the utilization of NiFe-LDH catalyst in water and organics electrooxidation.

Automatic rehabilitation exercise task assessment of stroke patients based on wearable sensors with a lightweight multichannel 1D-CNN model.

Approximately 75% of stroke survivors have movement dysfunction. Rehabilitation exercises are capable of improving physical coordination. They are mostly conducted in the home environment without guidance from therapists. It is impossible to provide timely feedback on exercises without suitable devices or therapists. Human action quality assessment in the home setting is a challenging topic for current research. In this paper, a low-cost HREA system in which wearable sensors are used to collect upper limb exercise data and a multichannel 1D-CNN framework is used to automatically assess action quality. The proposed 1D-CNN model is first pretrained on the UCI-HAR dataset, and it achieves a performance of 91.96%. Then, five typical actions were selected from the Fugl-Meyer Assessment Scale for the experiment, wearable sensors were used to collect the participants' exercise data, and experienced therapists were employed to assess participants' exercise at the same time. Following the above process, a dataset was built based on the Fugl-Meyer scale. Based on the 1D-CNN model, a multichannel 1D-CNN model was built, and the model using the Naive Bayes fusion had the best performance (precision: 97.26%, recall: 97.22%, F1-score: 97.23%) on the dataset. This shows that the HREA system provides accurate and timely assessment, which can provide real-time feedback for stroke survivors' home rehabilitation.

A novel chlorin derivative Shengtaibufen (STBF) mediated photodynamic therapy combined with iodophor for the treatment of chronic superficial leg wounds infected with methicillin-resistant Staphylococcus aureus: A retrospective clinical study.

OBJECTIVE: Chronic wounds are costly and difficult to treat, resulting in morbidity and even mortality in some cases due to a high methicillin-resistant Staphylococcus aureus (MRSA) burden contributing to chronicity. We aimed to observe the antimicrobial activity and healing-promoting effect of a novel photosensitizer Shengtaibufen (STBF)-mediated antibacterial photodynamic therapy (PDT) on MRSA-infected chronic leg ulcers. PATIENTS AND METHODS: This was a retrospective, comparative, single-center clinical study. A total of 32 patients with chronic lower limb wounds infected with MRSA from January 2022 to December 2023 were finally included in this study by searching the electronic medical records of the dermatology department of Huadong Hospital, including a group of red light combined with iodophor (control+iodophor, n=16, receiving red light once a week for 8 weeks and routine dressing change with iodophor once a day) and a group of STBF-mediated PDT (STBF-PDT) combined with iodophor (STBF-PDT+iodophor, n=16, receiving STBF-PDT and routine dressing change with iodophor once a day). STBF-PDT was performed once a week (1 mg/ml STBF, 1 h incubation, 630 nm red light, 80 J/cm2) for 8 weeks. The primary endpoints included wound clinical signs, wound size, wound-related pain, re-epithelialization score, MRSA load and wound-related quality of life (wound-QoL). Any adverse events were also recorded. RESULTS: We found that STBF-PDT+iodophor could effectively alleviate clinical infection symptoms, accelerate wound closure, reduce average biological burden and improve wound-QoL without severe adverse events in comparison to the control+iodophor group. The STBF-PDT+iodophor group obtained a mean percentage reduction of 65.22% in wound size (from 18.96±11.18 cm2 to 6.59±7.94 cm2) and excellent re-epithelialization scores, as compared with a decrease of 30.17% (from 19.23±9.80 cm2 to 13.43±9.32 cm2) for the control+iodophor group. Significant differences in wound area were observed at week 6 (p=0.028*) and week 8 (p=0.002**). The bacterial load decreased by 99.86% (from 6.45 × 107±2.69 × 107 to 8.94 × 104±1.92 × 105 CFU/cm2, p<0.0001) in the STBF-PDT+iodophor group and 1.82% (from 6.61 × 107±2.13 × 107 to 6.49 × 107±2.01 × 107 CFU/cm2, p=0.029) in the control+iodophor group. The wound-QoL in STBF-PDT+iodophor group had a 51.62% decrease in overall score (from 29.65±9.33 at the initial to 14.34±5.17 at week 8, p<0.0001) compared to those receiving red light and routine wound care (from 30.73±17.16 to 29.32±15.89 at week 8, p=0.003). Moreover, patients undergoing STBF-PDT+iodophor exhibited great improvements in all domains of wound-QoL (physical, psychological and everyday-life), whereas the control+iodophor group ameliorated in only one field (everyday-life). CONCLUSION: Our data confirmed that a novel photosensitizer, STBF-mediated PDT, when combined with iodophor, served as a potential modality for MRSA infection and a possible therapy for other drug-resistant microorganisms, and as a promising alternative for chronic cutaneous infectious diseases.

Chloroplast and whole-genome sequencing shed light on the evolutionary history and phenotypic diversification of peanuts.

Cultivated peanut (Arachis hypogaea L.) is a widely grown oilseed crop worldwide; however, the events leading to its origin and diversification are not fully understood. Here by combining chloroplast and whole-genome sequence data from a large germplasm collection, we show that the two subspecies of A. hypogaea (hypogaea and fastigiata) likely arose from distinct allopolyploidization and domestication events. Peanut genetic clusters were then differentiated in relation to dissemination routes and breeding efforts. A combination of linkage mapping and genome-wide association studies allowed us to characterize genes and genomic regions related to main peanut morpho-agronomic traits, namely flowering pattern, inner tegument color, growth habit, pod/seed weight and oil content. Together, our findings shed light on the evolutionary history and phenotypic diversification of peanuts and might be of broad interest to plant breeders.

"Hepatic hilum area priority, liver posterior first": An optimized strategy in laparoscopic resection for type III-IV hilar cholangiocarcinoma.

BACKGROUND: In recent years, pure laparoscopic radical surgery for Bismuth-Corlette type III and IV hilar cholangiocarcinoma (HCCA) has been preliminarily explored and applied, but the surgical strategy and safety are still worthy of further improvement and attention. AIM: To summarize and share the application experience of the emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types III and IV. METHODS: The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types III and IV who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed. RESULTS: Among the 6 patients, 4 were males and 2 were females. The average age was 62.2 ± 11.0 years, and the median body mass index was 20.7 (19.2-24.1) kg/m2. The preoperative median total bilirubin was 57.7 (16.0-155.7) µmol/L. One patient had Bismuth-Corlette type IIIa, 4 patients had Bismuth-Corlette type IIIb, and 1 patient had Bismuth-Corlette type IV. All patients successfully underwent pure laparoscopic radical resection following the strategy of "hepatic hilum area dissection priority, liver posterior separation first". The operation time was 358.3 ± 85.0 minutes, and the intraoperative blood loss volume was 195.0 ± 108.4 mL. None of the patients received blood transfusions during the perioperative period. The median length of stay was 8.3 (7.0-10.0) days. Mild bile leakage occurred in 2 patients, and all patients were discharged without serious surgery-related complications. CONCLUSION: The emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types III and IV. This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA, shortens the learning curve, and is worthy of further clinical application.

Spin-Orbit-Locking Chiral Bound States in the Continuum.

Bound states in the continuum (BICs), which are confined optical modes exhibiting infinite quality factors and carrying topological polarization configurations in momentum space, have recently sparked significant interest across both fundamental and applied physics. Here, we show that breaking time-reversal symmetry by an external magnetic field enables a new form of chiral BICs with spin-orbit locking. Applying a magnetic field to a magneto-optical photonic crystal slab lifts doubly degenerate BICs into a pair of chiral BICs carrying opposite pseudospins and orbital angular momenta. Multipole analysis verifies the nonzero angular momenta and reveals the spin-orbital-locking behaviors. In momentum space, we observe ultrahigh quality factors and near-circular polarization surrounding chiral BICs, enabling potential applications in spin-selective nanophotonics. Compared to conventional BICs, the magnetically induced chiral BICs revealed here exhibit distinct properties and origins, significantly advancing the topological photonics of BICs by incorporating broken time-reversal symmetry.

Pharmacological inhibition of Septins with Forchlorfenuron attenuates thrombus formation in experimental thrombotic mice models with modulating multiple signaling pathways in platelets.

INTRODUCTION: The Septin family of cytoskeletal proteins is abundant in platelets. When these proteins are functionally blocked using the compound forchlorfenuron (FCF), it hampers the normal activation processes of purified human platelets. OBJECTIVES: To evaluate the in vivo effects of FCF on physiological haemostasis and pathological thrombosis in mice and to investigate possible molecular mechanisms. METHODS: The impact of FCF on haemorrhage risk in the brain, liver, and tail of mice was investigated. Using several experimental models, thrombus development in the lung, mesenteric arteries, and postcava was studied. Functional assays were performed on mice and human platelets, both with and without FCF pretreatment. These tests included aggregation, granule release, ROS production, integrin αIIbß3 activation, cytoskeletal remodeling imaging, and clot retraction. RESULTS: Neither oral nor intravenous administration of FCF showed any apparent impairment of haemostasis in the tissues studied, but only later administration resulted in a significant reduction in thrombus formation in different mice vessel types. FCF generally inhibited agonist-induced platelet aggregation, degranulation, ROS burst, morphological expansion on the fibrinogen matrix with completely disordered dynamic organizations of the cytoskeleton for septin, tubulin and actin. In addition, FCF was found to antagonise agonist-induced dephosphorylation of VASP (Ser239) and PI3K/AKT and ERK1/2 phosphorylation. CONCLUSION: FCF showed preferences in attenuating pathological thrombus formation, apart from physiological haemostasis, with possible mechanisms to prevent cytoskeletal remodelling and signal transduction of AKT, ERK1/2 and VASP signalling pathways, suggesting that Septin may serve as a promising target for the prevention and treatment of thrombotic diseases.

Metalenses phase characterization by multi-distance phase retrieval.

Metalens, characterized by their unique functions and distinctive physical properties, have gained significant attention for their potential applications. To further optimize the performance of metalens, it is necessary to characterize the phase modulation of the metalens. In this study, we present a multi-distance phase retrieval system based on optical field scanning and discuss its convergence and robustness. Our findings indicate that the system is capable of retrieving the phase distribution of the metalens as long as the measurement noise is low and the total length of the scanned light field is sufficiently long. This system enables the analysis of focal length and aberration by utilizing the computed phase distribution. We extend our investigation to measure the phase distribution of the metalens operating in the near-infrared (NIR) spectrum and identify the impact of defects in the sample on the phase. Additionally, we conduct a comparative analysis of the phase distribution of the metalens in air and ethanol and observe the variations in the phase modulation of the metalens in different working mediums. Our system provides a straightforward method for the phase characterization of metalens, aiding in optimizing the metalens design and functionality.

Identification and analysis of key genes related to efferocytosis in colorectal cancer.

The impact of efferocytosis-related genes (ERGs) on the diagnosis of colorectal cancer (CRC) remains unclear. In this study, efferocytosis-associated biomarkers for the diagnosis of CRC were identified by integrating data from transcriptome sequencing and public databases. Finally, the expression of biomarkers was validated by real-time quantitative polymerase chain reaction (RT-qPCR). Our study may provide a reference for CRC diagnosis. BACKGROUND: It has been shown that some efferocytosis related genes (ERGs) are associated with the development of cancer. However, it is still uncertain how ERGs may influence the diagnosis of colorectal cancer (CRC). METHODS: In our study, the CRC cohorts were gained from transcriptome sequencing and the gene expression omnibus (GEO) database (GSE71187). Efferocytosis related biomarkers with diagnostic utility for CRC were identified through combining differentially expressed analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. Then, infiltration abundance of immune cells between CRC and control was evaluated. The regulatory networks (including mRNA-miRNA-lncRNA and miRNA/transcription factors (TF)-mRNA networks) were created. Finally, the expression of biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: There were 3 biomarkers (ELMO3, P2RY12, and PDK4) related diagnosis for CRC patients gained. ELMO3 was highly expressed in CRC group, while P2RY12 and PDK4 was lowly expressed. Besides, the infiltrating abundance of 3 immune cells between CRC and control groups was significantly differential, namely activated CD4 memory T cells, macrophages M0, and resting mast cells. We then constructed a mRNA-miRNA-lncRNA network containing 3 mRNAs, 33 miRNAs, and 22 lncRNAs, and a miRNA/TF-mRNA network including 3 mRNAs, 33 miRNAs, and 7 TFs. Additionally, RT-qPCR results revealed that the expression trends of all biomarkers were consistent with the transcriptome sequencing data and GSE71187. CONCLUSION: Taken together, this study provides three efferocytosis related biomarkers (ELMO3, P2RY12, and PDK4) for diagnosis of CRC, providing a scientific reference for further studies of CRC.

Danggui-Shaoyao-San protects against non-alcoholic steatohepatitis via modulation of hepatic APP protein, Lysosomal CTSB release, and NF-κB activation.

Background: Non-alcoholic steatohepatitis (NASH), an escalating global health concern, is a primary factor behind cirrhosis, liver transplantation, and hepatocellular carcinoma. Effective treatments remain elusive. Danggui-Shaoyao-San (DGSY), a classic famous prescription employed in treating NASH, could hold promise, although its molecular underpinnings are still under investigation. This study undertakes an exploration of the impacts of DGSY on NASH and seeks to illuminate the mechanisms at play. Methods: UHPLC-Q-Orbitrap HRMS was employed to identify compounds within DGSY. Mice underwent a 25-week regimen of HFHC diet and high-sugar water, with 4 weeks of DGSY treatment for efficacy and pathogenic mechanism exploration in vivo. L02 cells were cultured with 0.2 mM FFA for 24 h, exposed to DGSY at 1 mg/ml and 2 mg/ml for efficacy and pathogenic mechanism exploration in vitro. Using online databases, we sought potential targets for NASH treatment, and through PPI networks, identified key targets. Expression levels of genes and proteins were examined by western blotting, RT-PCR, and immunofluorescence staining. Results: Thirty-four compounds were identified within DGSY. DGSY brought about marked reductions in biochemical indicators and yielded significant improvements in NASH mice histological features. Additionally, it mitigated hepatic steatosis and inflammation both in vivo and in vitro. The top 10 targets from two network pharmacology analyses, one focusing on structural prediction and the other on literature mining, identified APOE and APP as potential therapeutic targets for DGSY in NASH treatment. PCR validation confirmed that DGSY reduced APP expression after treatment, and further investigation revealed that DGSY significantly suppressed hepatic APP and Aß expression, indicating its effectiveness in treating NASH. Furthermore, it inhibited Aß-induced Cathepsin B lysosomal release, reducing hepatic inflammation. Conclusion: Danggui-Shaoyao-San has anti-steatohepatitis effects in ameliorating hepatic APP protein expression, reducing hepatic lysosomal CTSB release, and suppressing hepatic NF-κB activation. The study provided a more theoretical basis for the future clinical application of DGSY.

PTBP3 Mediates IL-18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer.

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA-seq analysis, it is found high expression of the splicing factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping of interleukin-18 (IL-18), resulting in the expression of ΔIL-18, an isoform specifically expressed in tumors. That ΔIL-18 promotes GBC immune escape by down-regulating FBXO38 transcription levels in CD8+T cells to reduce PD-1 ubiquitin-mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL-18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL-18 production displayed anti-tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL-18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL-18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL-18 pre-mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.

Circadian Rhythm and Nitrogen Metabolism Participate in the Response of Boron Deficiency in the Root of Brassica napus.

Boron (B) deficiency has been shown to inhibit root cell growth and division. However, the precise mechanism underlying B deficiency-mediated root tip growth inhibition remains unclear. In this study, we investigated the role of BnaA3.NIP5;1, a gene encoding a boric acid channel, in Brassica napus (B. napus). BnaA3.NIP5;1 is expressed in the lateral root cap and contributes to B acquisition in the root tip. Downregulation of BnaA3.NIP5;1 enhances B sensitivity in B. napus, resulting in reduced shoot biomass and impaired root tip development. Transcriptome analysis was conducted on root tips from wild-type B. napus (QY10) and BnaA3.NIP5;1 RNAi lines to assess the significance of B dynamics in meristematic cells during seedling growth. Differentially expressed genes (DEGs) were significantly enriched in plant circadian rhythm and nitrogen (N) metabolism pathways. Notably, the circadian-rhythm-related gene HY5 exhibited a similar B regulation pattern in Arabidopsis to that observed in B. napus. Furthermore, Arabidopsis mutants with disrupted circadian rhythm (hy5/cor27/toc1) displayed heightened sensitivity to low B compared to the wild type (Col-0). Consistent with expectations, B deficiency significantly disrupted N metabolism in B. napus roots, affecting nitrogen concentration, nitrate reductase enzyme activity, and glutamine synthesis. Interestingly, this disruption was exacerbated in BnaA3NIP5;1 RNAi lines. Overall, our findings highlight the critical role of B dynamics in root tip cells, impacting circadian rhythm and N metabolism, ultimately leading to retarded growth. This study provides novel insights into B regulation in root tip development and overall root growth in B. napus.

A Small "Tent" in the Esophagus.

Cite this article as: Zong Z, Xu J, Zhang H, Xu H, Tang X, Shi L. A small "tent" in the esophagus. Turk J Gastroenterol. 2024;35(7): 587-588.

Prognostic implications of lymph node yield in pediatric patients with N1b papillary thyroid cancer.

OBJECTIVE: To investigate whether lymph node (LN) yield influences clinical outcomes for pediatric patients with laterocervical lymph node metastasis (N1b) from papillary thyroid cancer (PTC). METHODS: Conducted from January 1, 2008, to December 31, 2022, this was a cohort study of pediatric patients (aged ≤ 18 years) with N1b PTC who underwent total thyroidectomy and therapeutic LN dissection in the central and lateral compartments at 3 hospitals in southwest China in 2008-2021, with follow-up until 2022. Patients with distant metastasis were excluded. Univariate and multivariate Cox proportional hazards regression analyses were used to identify factors associated with persistent/recurrent diseases. RESULTS: A total of 102 pediatric patients (median [range] age, 16 [6-18] years) were analyzed: 36 patients (35 %) with T1; 27 patients (26 %), T2; 18 patients (18 %), T3; and 21 patients (21 %), T4. During a median follow-up of 50 months (range, 12-154 months), persistent diseases occurred in 40 (39 %) patients. Receiver operating characteristic analysis identified LN yield cut-off (<42 LNs) to predict persistent diseases. Multivariate analysis revealed that a less-extensive lymphadenectomy (<42 LNs) was an independent risk factor for persistent diseases (hazard ratio, 2.4; 95 % confidence intervals, 1.09-5.29; P=.029). CONCLUSIONS: Our study highlights that a higher LN yield may favorably influence prognosis in pediatric patients with N1b PTC.

A high functional cure rate was induced by pegylated interferon alpha-2b treatment in postpartum hepatitis B e antigen-negative women with chronic hepatitis B virus infection: an exploratory study.

Background and aims: Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure. Methods: A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks. Results: At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported. Conclusion: Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.

Revealing the nature of covalently tethered distonic radical anions in the generation of heteroatom-centered radicals: evidence for the polarity-matching PCET pathway.

Recognition of the intermediacy and regulation of reactivity patterns of radical intermediates in radical chemistry have profound impacts on harnessing and developing the full potential of open-shell species in synthetic settings. In this work, the possibility of in situ formation of O/N-X intermediates from Brønsted base covalently tethered carbonyl hypohalites (BCTCs) for the generation of heteroatom-centered radicals has certainly been excluded by NMR experiments and density functional theory calculations. Instead, the spectroscopic analyses reveal that the BCTCs serve as precursors of tether-tunable distonic radical anions (TDRAs) which have been unequivocally substantiated to be involved in the direct cleavage of O/N-H bonds to generate the corresponding heteroatom-centered radicals. Meanwhile, a deep insight into the properties and reactivities of the resulting TDRAs indicates that the introduction of a tethered Brønsted base on the parent open-shell species reinforces their stabilities and leads to a reversal of electrophilicity. Moreover, the dual descriptor values and electrophilicity indices are calculated based on eleven reported radical reactions involving various electrophilic/nucleophilic radical species, further confirming their validity in the prediction of the polar effect and the polarity-matching consistency between nucleophilic TDRAs and protic O/N-H bonds. The additional halogen-free experiments mediated by the combination of phthaloyl peroxide and TEMPO also prove the feasibility of the TDRA-assisted philicity-regulation approach. Lastly, detailed intrinsic bond orbital (IBO) and Hirschfeld spin population analyses are employed to elucidate that the H-atom abstraction processes are the polarity-matching proton-coupled electron transfer (PCET) pathways, with a degree of oxidative asynchronicity.

Biomarkers associated with immune-related adverse events induced by immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) constitute a pivotal class of immunotherapeutic drugs in cancer treatment. However, their widespread clinical application has led to a notable surge in immune-related adverse events (irAEs), significantly affecting the efficacy and survival rates of patients undergoing ICI therapy. While conventional hematological and imaging tests are adept at detecting organ-specific toxicities, distinguishing adverse reactions from those induced by viruses, bacteria, or immune diseases remains a formidable challenge. Consequently, there exists an urgent imperative for reliable biomarkers capable of accurately predicting or diagnosing irAEs. Thus, a thorough review of existing studies on irAEs biomarkers is indispensable. Our review commences by providing a succinct overview of major irAEs, followed by a comprehensive summary of irAEs biomarkers across various dimensions. Furthermore, we delve into innovative methodologies such as machine learning, single-cell RNA sequencing, multiomics analysis, and gut microbiota profiling to identify novel, robust biomarkers that can facilitate precise irAEs diagnosis or prediction. Lastly, this review furnishes a concise exposition of irAEs mechanisms to augment understanding of irAEs prediction, diagnosis, and treatment strategies.

Association of dietary behavior patterns of middle-aged and older adults with their obesity metabolic phenotype: a cross-sectional study.

BACKGROUND: Middle-aged and elderly individuals are the most susceptible groups for metabolic diseases, with their dietary behaviors being significant influencing factors. Exploring the association between overall dietary behaviors and obesity metabolic phenotypes is crucial for early prevention and control of chronic diseases, precision treatment and personalized interventions. METHODS: We conducted a cross-sectional study of 15,160 middle-aged and older adults between June 2019 and August 2021 to collect information on their body mass index (BMI), biochemical indices and disease history. The population was classified into four categories by the criteria of obesity metabolic phenotypes: metabolically healthy non-obesity (MHNO), metabolically unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). Scores were calculated based on compliance with healthy eating behavior patterns (appropriate or light dietary taste, moderately soft and hard food, slightly hot food temperature, medium or slow eating speed, daily intake of dietary supplements and eating with others), and the population was categorized into subgroups 0-2 (did not meet and met only 1 or 2), 3-4 (met 3 or 4), 5-6 (met 5 or 6). The relationship between dietary behavior patterns and different obesity metabolic phenotypes in middle-aged and elderly people were analyzed by multi-categorical logistic regression model. RESULTS: Compared with the 5-6 subgroup, the dietary behavior patterns of 0-2 and 3-4 scores were risk factors for MUNO, MHO and MUO (P < 0.05), and the lower the scores of the dietary behavior patterns, the higher the multiplicity of the occurrence of MUNO, MHO and MUO, especially for females and adults between 45-60 years old. Appropriate or light dietary taste, moderately soft and hard food, and slightly hot food temperature were protective factors for MUNO and MUO (P < 0.05); medium or slow eating speed and daily intake of dietary supplements were protective factors for MUNO, MHO and MUO (P < 0.05). CONCLUSION: Dietary behavior patterns in middle-aged and older adults are associated with different obesity metabolic phenotypes, and healthy dietary behaviors may be beneficial for the prevention and control of MUNO, MHO and MUO.