Stem-like CD8 T cells in stage I lung adenocarcinoma as a prognostic biomarker: A preliminary study.

OBJECTIVES: This study aimed to investigate the presence of stem-like CD8 T (CD8 TSL) cells in lung adenocarcinoma (LUAD) and explore their relationships with the clinical outcomes. METHODS: Multiplex immunofluorescence (mIF) was performed to identify CD8 TSL and antigen-presenting cells (APC) in 76 LUAD patients. Differences in the number of CD8 TSL cells based on tumor stage and the spatial relationships between CD8 TSL cells and APC niches were determined. The optimal cutoff value of CD8 TSL cells for predicting survival in patients with stage I LUAD was calculated. RESULTS: CD8 TSL cells were present in all tumors, and their numbers were significantly higher in stage I patients than in stage III patients (P = 0.010); CD8 TSL cells located in the APC niches accounted for 69.7% (53/76) of the hotspot fields. The optimal cutoff value for the number of CD8 TSL cells required to predict the overall survival (OS) in patients with stage I LUAD was 2.5 per 10000 µm2. The median OS and progression-free survival (PFS) in the high-level group (>2.5) were significantly (P < 0.001) longer than those in the low-level group (≤2.5). The number of CD8 TSL cells was an independent prognostic factor for stage I LUAD. Patients with more CD8 TSL cells had a lower risk of death and disease progression than those with less CD8 TSL cells. CONCLUSION: CD8 TSL cells were observed in patients with stages I-III LUAD and might serve as prognostic biomarkers for stage I LUAD.

Chemotherapy-related symptoms in children with leukemia: application of latent profile analysis and network analysis.

PURPOSE: Children with leukemia may experience a range of chemotherapy-related symptoms. Identifying subgroups and their distinct characteristics of symptoms may improve symptom management. We aimed to identify subgroups and their distinct characteristics of chemotherapy-related symptoms in children with leukemia. METHODS: A cross-sectional survey was conducted among 500 children with leukemia, who completed questionnaires that assessed their demographic and clinical characteristics, as well as the Memorial Symptom Assessment Scale. Latent profile analysis was conducted to identify subgroups of symptoms. Additionally, multiple regression analysis and network analysis were utilized to reveal the characteristics of each subgroup. RESULTS: Four subgroups were identified: "Profile 1: low symptom burden subgroup" (26.2%), "Profile 2: moderate symptom burden subgroup in transitional period" (14.8%), "Profile 3: moderate psychological symptom burden subgroup" (35.6%), and "Profile 4: high symptom burden subgroup" (23.4%). Multiple logistic regression analysis indicated that lower primary caregiver's education level, lower family monthly income, self-paid medical expenses, induction remission period, and consolidation enhancement period were associated with more severe symptoms of subgroups. Network analysis further revealed that nausea was the core symptom in Profiles 1 and 2, while the core symptom in Profile 3 was "I don't look like myself." Additionally, worrying was the core symptom in Profile 4. CONCLUSION: There exists heterogeneity in chemotherapy-related symptoms. Four subgroups and their corresponding characteristics of children with varying symptom severity were identified. Identifying these subgroups will facilitate personalized care, maximize intervention effectiveness, and alleviate symptom burden.

Liquid Metal Nanoparticles Physically Hybridized with Cellulose Nanocrystals Initiate and Toughen Hydrogels with Piezoionic Properties.

Liquid metal (LM) particles can serve as initiators, functional fillers, and cross-linkers for hydrogels. Herein, we show that cellulose nanocrystals (CNCs) stabilize LM particles in aqueous solutions, such as those used to produce hydrogels. The CNC-coated LM particles initiate free-radical polymerization to form poly(acrylic acid) (PAA) hydrogel with exceptional properties─stretchability ∼2000%, excellent toughness ∼1.8 MJ/m3, mechanical resilience, and efficient self-healing─relative to cross-linked PAA networks polymerized using conventional molecular initiators. FTIR spectroscopy, rheology, and mechanical measurements suggest that physical bonds between PAA and both Ga3+ and LM-CNC particles contribute to the excellent mechanical properties. The gels are used to sense a wide range of strains, such as those associated with human motion, via changes in resistance through the gel. The sensitivity at low strains enables monitoring subtle physiological signals, such as pulse. Without significantly compromising the toughness, soaking the gels in salt solution brings about high ionic conductivity (3.8 S/m), enabling them to detect touch via piezoionic principles; the anions in the gel have higher mobility than cations, resulting in significant charge separation (current ∼30 µA, ∼10 µA/cm2) through the gel in response to touch. These attractive properties are promising for wearable sensors, energy harvesters, and self-powered ionic touch panels.

Association between oxidative balance score and metabolic syndrome and its components in US adults: a cross-sectional study from NHANES 2011-2018.

Background: Metabolic syndrome (MetS) is a global health concern that threatens human well-being. The oxidative balance score (OBS) is a tool to identify the level of oxidative stress that is correlated with MetS risk. However, association between OBS and MetS and its components has not been reported. Methods: This cross-sectional study included adult individuals with complete OBS and MetS data from National Health and Nutrition Examination Survey (NHANES) 2011-2018. A weighted logistic regression analysis was conducted to identify the association of the total, dietary, and lifestyle OBS scores with MetS. Subgroup analyses and restricted cubic splines were used to further explore associations. Results: In total, 10,025 eligible adult individuals (51.48% were males at a median age of 46 years) were included, with a MetS prevalence of 29.98%. In fully adjusted model, higher total OBS was associated with reduced risk of MetS (Q3 vs. Q1: odds ratio [OR] = 0.57, 95% confidence interval [CI], 0.46-0.71, p < 0.001; Q4 vs. Q1: OR = 0.42, 95% CI, 0.33-0.53, p < 0.001; P for trend <0.001). Significant differences were observed in the relationship between dietary OBS and lifestyle OBS and MetS risk (continuous dietary OBS: OR = 0.97, 95% CI, 0.96-0.98, p < 0.001; continuous lifestyle OBS: OR = 0.61, 95% CI, 0.58-0.64, p < 0.001), as well as negative relationship between total OBS and risk of five MetS components (all p < 0.05). Subgroup analysis showed marital status modified the negative association between OBS and MetS in subgroup analysis (P for interaction = 0.014). Moreover, a nonlinear correlation between OBS and MetS (including its components) was found, further elucidating associations (all p < 0.05). Restricted cubic splines demonstrated not obviously U-shape correlation between OBS and MetS components (elevated triglyceride and blood pressure). Conclusion: This study suggests a strong association between the OBS and MetS and its components. Our data indicated that a higher OBS score was correlated with a decreased risk of MetS and its components in a nonlinear manner. Hence, the OBS may serve as an effective marker for identifying individuals with MetS, with a higher score indicating a predominance of more antioxidants.

De novo synthesis of inherently chiral heteracalix[4]aromatics from enantioselective macrocyclization enabled by chiral phosphoric acid-catalyzed intramolecular SNAr reaction.

We report herein the synthesis of highly enantiopure inherently chiral N3,O-calix[2]arene[2]triazines from enantioselective macrocyclization enabled by chiral phosphoric acid-catalyzed intramolecular nucleophilic aromatic substitution reaction. In contrast to documented examples, the inherent chirality of the acquired compounds arises from one heteroatom difference in the linking positions of heteracalix[4](het)arenes.

Interleukin-36 is overexpressed in human sepsis and IL-36 receptor deletion aggravates lung injury and mortality through epithelial cells and fibroblasts in experimental murine sepsis.

BACKGROUND: Sepsis is defined as a life-threatening syndrome caused by an unbalanced host response to infection. The role of interleukin (IL)-36 cytokines binding to the IL-36 receptor (IL-36R) in host response during sepsis remains unknown. METHODS: Serum IL-36 level was measured in 47 septic patients sampled on the day of intensive care unit (ICU) and emergency department admission, 21 non-septic ICU patient controls, and 21 healthy volunteers. In addition, the effects of IL-36R deletion on host inflammatory response in cecal ligation and puncture (CLP)-induced polymicrobial sepsis was determined. RESULTS: On the day of ICU and emergency department admission, the patients with sepsis showed a significant increase in serum IL-36 levels compared with ICU patient controls and healthy volunteers, and the serum IL-36 levels were related to the severity of sepsis. Non-survivors of septic patients displayed significantly lower serum IL-36 levels compared with survivors. A high serum IL-36 level in ICU and emergency department admission was associated with 28-day mortality, and IL-36 was found to be an independent predictor of 28-day mortality in septic patients by logistic regression analysis. Furthermore, IL-36R deletion increased lethality in CLP-induced polymicrobial sepsis. Septic mice with IL-36R deletion had higher bacterial load and demonstrated more severe multiple organ injury (including lung, liver, and kidney) as indicated by clinical chemistry and histopathology. Mechanistically, IL-36R ligands released upon lung damage activated IL-36R+lung fibroblasts thereby inducing expression of the antimicrobial protein lipocalin 2. Moreover, they induced the apoptosis of lung epithelial cells. CONCLUSIONS: Septic patients had elevated serum IL-36 levels, which may correlate with disease severity and mortality. In experimental sepsis, we demonstrated a previously unrecognized role of IL-36R deletion in increasing lethality.

Fasting blood glucose predicts high risk of in-stent restenosis in patients undergoing primary percutaneous coronary intervention: a cohort study.

Objectives. Studies have shown that fasting blood glucose (FBG) is closely associated with poor prognosis in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI), but its association with in-stent restenosis (ISR) is still unclear. Therefore, this study was to explore the association between FBG with ISR in patients with CHD after PCI. Design. In this cohort study, we included 531 patients with CHD who underwent PCI. Logistic regression, receiver operating characteristic (ROC), subgroup analysis and restricted cubic spline (RCS) were used to assess the association between FBG with ISR. Results. A total of 124 (23.4%) patients had ISR. Patients with higher levels of FBG had higher incidence of ISR compared to those with lower levels of FBG (p = 0.002). In multivariable logistic regression analyses, higher levels of FBG remained strongly associated with higher risk of ISR (as a categorical variable, OR: 1.89, 95% CI: 1.21-2.94, p = 0.005; as a continuous variable, OR: 1.12, 95% CI: 1.03-1.23, p = 0.011). ROC analysis also showed that FBG might be associated with the occurrence of ISR (AUC = 0.577, 95% CI: 0.52-0.64, p = 0.013). Subgroup analyses showed the association of FBG with ISR was also stable in several subgroups (< 60 years or ≥ 60 years, male, with or without smoking, without diabetes and without hypertension). And RCS analysis showed that FBG was linearly and positively associated with the risk of ISR. Conclusions. Higher levels of FBG were closely associated with higher risk of ISR in patients with CHD after PCI.

Exploring core symptoms and interrelationships among symptoms in children with acute leukemia during chemotherapy: A network analysis.

PURPOSE: Children with acute leukemia have suffered from a considerable symptom burden during chemotherapy. However, few studies have focused on exploring the mechanisms among symptoms in children with acute leukemia. Our study aims to explore core symptoms and describe the interrelationships among symptoms in children with acute leukemia during chemotherapy. METHODS: From January 2021 to March 2023, 469 children with acute leukemia were recruited from 20 Chinese cities. The Memorial Symptom Assessment Scale 10-18 (MSAS 10-18) was used to evaluate the prevalence and severity of symptoms during chemotherapy. A network analysis was performed by the R software based on 31 symptoms. Centrality indices and density were used to explore core symptoms and describe interrelationships among symptoms in the network during chemotherapy. RESULTS: Worrying and feeling irritable were the central symptoms across the three centrality indices, including strength, closeness, and betweenness. Lack of energy was the most prevalent symptom; however, it was less central than other symptoms. The density of the "induction and remission" network significantly differed from other cycles' counterparts (p < 0.001). Global strength was greater in the " ≥ 8 years group " network than the " < 8 years group " network (p = 0.023). CONCLUSION: Network analysis provides a novel approach to identifying the core symptoms and understanding the interrelationships among symptoms. Our study indicates the need to assess emotional symptoms in children with acute leukemia during chemotherapy, especially during the induction and remission phases, as well as in older children. Future research is imperative to construct trajectories of dynamic symptom networks and centrality indices in longitudinal data to investigate the causal relationships among symptoms.

Identifying central symptom clusters and correlates in children with acute leukemia undergoing chemotherapy: a network analysis.

Background: Previous studies have examined symptom clusters in children with acute leukemia, yet a knowledge gap persists regarding central symptom clusters and their influencing factors. By identifying these central clusters and associated factors, healthcare providers can enhance their understanding and effective management of symptoms. Our study seeks to address this gap by identifying symptom clusters, exploring central clusters, and investigating the demographic and health-related factors associated with these clusters in children with acute leukemia undergoing chemotherapy. Methods: A total of 586 children with acute leukemia from January 2021 to April 2023 were recruited from China. They were investigated using Memorial Symptom Assessment Scale 10-18 during chemotherapy. The principal component analysis was used to identify the symptom clusters. An association network was conducted to describe the relationships among symptoms and clusters. A multiple linear model was used to investigate the associated factors for the severity of overall symptoms and each symptom cluster. Results: Five clusters were identified, including oral and skin cluster, somatic cluster, self-image disorder cluster, gastrointestinal cluster and psychological cluster. Gastrointestinal cluster was the most central symptom cluster. Age, sex, clinical classification, number of having chemotherapy and education degree and marital status of the primary caregiver are associated with the severity of these five symptom clusters. Conclusion: Our study highlights the importance of evaluating symptom clusters in children with acute leukemia during chemotherapy. Specifically, addressing gastrointestinal symptoms is crucial for effective symptom management and overall care.

Tetrahomo corona[4]arene-based spirophanes: synthesis, structure, and properties.

In contrast to a plethora of macrocyclic and cage compounds, spirophanes have remained largely unexplored. We report herein the construction, structure and properties of unprecedented tetrahomo corona[4]arene-based ditopic and tritopic macrocycles of spiro structures. Synthesis was conveniently achieved by means of an efficient SNAr reaction from simple and commercially available starting materials. Racemic samples were resolved into enantiopure chiral tetrahomo i-corona[4]arenes, spirophanes and bispirophanes which show interesting chiroptical properties. The acquired electron-deficient macrocyclic compounds were found to adopt unique conformational structures and to form distinct complexes with TTF in the solid state. Our study provides a new opportunity to develop multitopic macrocycles of different topologies which have potential applications in supramolecular chemistry.

Synthesis of Functionalized ABAC- and ABCD-Type Inherently Chiral Heteracalix[4]aromatics.

Despite their interesting stereochemistry and potential applications in (supramolecular) chemistry and chiroptical materials, inherently chiral macrocyclic compounds remain rare and are largely unexplored. We report herein a fragment coupling method to construct ABAC- and ABCD-type inherently chiral heteracalix[4]aromatics. The synthesis involves SNAr CuI-catalyzed Ullmann coupling and aliphatic nucleophilic substitution reactions as key steps using readily available starting materials. Postmacrocyclization functionalization reactions enabled the production of amino-substituted and (benzo[d])imidazole-2-(thi)one-bearing heteracalix[4]aromatics. Enantiopure ABCD-type macrocycles were obtained from resolution.

Asymmetric Synthesis of Enantioenriched Zigzag-Type Molecular Belts by Kinetic Resolution and Subsequent Transformations.

Asymmetric synthesis of enantioenriched zigzag-type molecular belts featuring copper/H8-binaphthol-catalyzed kinetic resolution of a resorcinarene derivative and subsequent transformations was developed. The acquired rigid and C4-symmetric belt exhibited remarkably enhanced photophysical and chiroptical properties in comparison to its conformationally fluxional macrocyclic precursor.

Functionalized Hydrocarbon Belts: Synthesis, Structure and Properties.

Hydrocarbon belts have drawn great attention because of their unique structures and tantalizing properties. Although a few belts and heteroatom-doped analogs have been synthesized, belt molecules containing non-hexagonal rings remain rare. Herein we report the construction and application of unprecedented zigzag-type hydrocarbon belts which contain functionalized eight-membered rings. The synthesis features fourfold intramolecular acylation reactions of resorcin[4]arene-derived intermediates, which affords C4 -symmetric tetrabenzobelt[4]arene[4]cyclooctatrienones. Stereoselective ketone reduction with LiAlH4 and nucleophilic addition with alkynyllithiums provide the corresponding tetrahydroxylated belts. The tetraol and its methyl ether are powerful and selective hosts to form 2 : 1 and 1 : 1 complexes with cesium ion, respectively, with binding constants up to (1.71±0.33)×1011  M-2 and (1.50±0.16)×106  M-1 . In addition, enantiopure C4 -symmetric belts can emit CPL with |glum | being around 0.01.

Oncology nurses' and oncologists' experience of addressing sexual health concerns in breast cancer patients: A qualitative study.

PURPOSE: This study aimed to explore the experiences of Chinese oncology nurses and oncologists who provide sexual health education for breast cancer patients in their practical work. METHODS: This was a qualitative study using semistructured face-to-face interviews. Eleven nurses and eight oncologists who provided sexual health education to breast cancer patients were purposively recruited from eight hospitals in seven provinces of China. Data were analyzed using the thematic analysis method. RESULTS: Four main themes emerged: the surface of sexual health, stress and benefit finding, cultural sensitivity and communication, needs and changes. Both oncology nurses and oncologists found it difficult to solve sexual health problems, which were beyond their responsibilities and competencies. They felt helpless about the limitations of external support. Nurses hoped oncologists could participate in more sexual health education. CONCLUSIONS: Oncology nurses and oncologists experienced great challenges in educating breast cancer patients about sexual health. They are eager to obtain more formal education and learning resources for sexual health education. Specific training to improve the sexual health education competence of healthcare professionals is needed. Furthermore, more support is needed to create conditions to encourage patients to reveal their sexual challenges. It is necessary for oncology nurses and oncologists to communicate on sexual health in breast cancer patients, and to promote interdisciplinary communication and share responsibility.

A Randomized Trial of Preoperative Planning of Left Atrial Appendage Occlusion Using Cardiac Computed Tomography Angiography.

Objective. To evaluate the value of individualized planning of left atrial appendage occlusion (LAAO) using cardiac computed tomography angiography (CCTA) reconstruction techniques. Methods. A total of 96 patients treated for LAAO with the Watchman occluder were included in this study. All patients were randomized by random number table in a 2:1 ratio into the CCTA (+) and CCTA (-) groups according to whether CCTA was performed preoperatively. 3D cardiac reconstruction was performed preoperatively in the CCTA (+) group to plan the location of the atrial septal puncture site, left atrial appendage(LAA) landing zone, predict the size of the occluder and simulate occluder release. In the CCTA(-) group, only transesophageal echocardiography (TEE) and fluoroscopy were used to guide LAAO. Results. The number of occluders used in a single procedure (1.06 ± .24 vs 1.22 ± .42), the number of intraoperative angiography positions (1.23 ± .58 vs 2.28 ± .85) and the procedure time (45.88 ± 5.08 vs 62.44 ± 5.60) in the CCTA(+) group were lower than in the CCTA(-) group (P < .05), and the first-attempt blocking success rate was higher than that of the CCTA(-) group (85.9% vs 65.6%, P = .021). Furthermore, the Bland-Altman plots showed good agreement between the longest diameter of the CCTA-predicted landing zone and the longest diameter of the actual landing zone (95% LoA -7.49, 10.24). A strong positive correlation was observed between the predicted compression ratio and the actual compression ratio (r = .890, P < .001). In addition, a strong positive correlation was found between the CCTA-predicted longest diameter of the landing zone and the actual occluder size (r = .863, P < .001). Conclusion. Accurate planning for LAAO using preoperative CCTA can reduce intraoperative angiography positions and occluder changes, shorten the procedure time, increase the success rate of first-attempt blocking and reduce the difficulty of the procedure.

A Novel D-π-A Type Fluorescent Probe for Cu2+ Based on Styryl-Pyridinium Salts Conjugating Di-(2-picolyl)amine (DPA) Units.

A novel D-π-A type fluorescent probe L(NO3) for Cu (II) sensing was designed and fully characterized. The probe consists of a styryl-pyridine cation fluorescent group and a di-(2-picolyl)amine (DPA) receptor unit, which are linked by a phenyl group to form an electron donor-π-acceptor (D-π-A) conjugate system, especially the introduction of a nitrate counter anion for significantly enhanced water solubility of the probe. Fluorescence titration studies of the probe L(NO3) showed a higher selectivity for Cu2+ than other metal ions, and the emission spectrum was strongly quenched upon binding. The competitive binding assay and the low detection limit (0.932 µM) showed that the probe L(NO3) had strong anti-interference ability and excellent Cu2+ detection performance. The binding ratio of probe L(NO3) and Cu2+ was determined from Job's plot to be 1:1, which is consistent with the results obtained from X-ray crystal structures. Meanwhile, the probe showed instantaneous chemical reversibility when titrated with EDTA solution, indicating potential recycling properties of the probe. In addition, the design of inexpensive fluorescent test strips can perform the on-site and real-time detection Cu2+ with a color recognition application.

Inherently chiral calixarenes by a catalytic enantioselective desymmetrizing cross-dehydrogenative coupling.

Under the catalysis of PdBr2 and a chiral phosphoramidite ligand, the upper-rim mono (2-bromoaroyl)-substituted calix[4]arene derivatives underwent a facile enantioselective desymmetrization reaction to afford 9H-fluorene-embedded inherently chiral calixarenes in good yields with excellent enantioselectivities. The transannular dehydrogenative arene-arene coupling reaction proceeded most probably through an oxidative addition of the Caryl-Br bond to a ligated palladium catalyst followed by a sequence of an enantioselective 1,5-palladium migration and an intramolecular C-H arylation sequence. This new family of inherently chiral calixarenes possesses unique chiroptical properties thanks to their highly rigid structure induced by the 9H-fluorene segment.

Highly Strained Oxygen-Doped Chiral Molecular Belts of the Zigzag-Type with Strong Circularly Polarized Luminescence.

Herein we report a two-directional cyclization strategy for the synthesis of highly strained depth-expanded oxygen-doped chiral molecular belts of the zigzag-type. From the easily accessible resorcin[4]arenes, an unprecedented cyclization cascade generating fused 2,3-dihydro-1H-phenalenes has been developed to access expanded molecular belts. Stitching up the fjords through intramolecular nucleophilic aromatic substitution and ring-closing olefin metathesis reactions furnished a highly strained O-doped C2 -symmetric belt. The enantiomers of the acquired compounds exhibited excellent chiroptical properties. The calculated parallelly aligned electric (µ) and magnetic (m) transition dipole moments are translated to the high dissymmetry factor (|glum | up to 0.022). This study provides not only an appealing and useful strategy for the synthesis of strained molecular belts but also a new paradigm for the fabrication of belt-derived chiroptical materials with high CPL activities.

Issues and prospects of image-guided thermal ablation in the treatment of primary and metastatic lung tumors.

The precise local minimally invasive or noninvasive treatment represents the important orientation for advancing the treatment of pulmonary malignant tumors. New local treatment methods have emerged as solutions to the shortcomings of minimally invasive or local treatment methods. Image-guided thermal ablation (IGTA) comes with the characteristics such as more accurate localization, less trauma, more definite efficacy, higher safety, stronger repeatability, fewer complications, and lower cost in treating lung tumors. This paper investigates the existing problems of IGTA in the treatment of lung tumors and puts forward the orientation of studies.