The role of radiotherapy in the treatment of sinonasal undifferentiated carcinoma: A population-based analysis.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive disease with ambiguous management and poor prognosis. This study aimed to evaluate the role of radiation therapy (RT) and explore the optimal treatment sequence. METHODS: Retrospective analysis of survival trends of 410 SNUC patients between 1973 and 2015. RESULTS: The 5-year cancer-specific survival (CSS) rate (45.1%) and overall survival (OS) rates (38.1%) were reported in the 84-month median follow-up. Radiotherapy was a prognosticator for improving CSS (hazard ratio [HR] = 0.425, 95% confidence interval [CI]: 0.299-0.603, p = 0.000) and OS (HR = 0.415, 95% CI: 0.303-0.570, p = 0.000), either with surgery (p = 0.000) or without surgery (p = 0.000). However, in a combined therapy of surgery and RT, preoperative and postoperative RT (5-year OS rates were 47.1% and 45.6%, respectively, p = 0.486) were not significantly different. CONCLUSIONS: Radiotherapy plays a key role in improving SNUC survival rates. No significant difference in survival rates was observed in preoperative and postoperative RT treatment.

Ni3C/Ni3S2 Heterojunction Electrocatalyst for Efficient Methanol Oxidation via Dual Anion Co-modulation Strategy.

Enhancing active states on the catalyst surface by modulating the adsorption-desorption properties of reactant species is crucial to optimizing the electrocatalytic activity of transition metal-based nanostructured materials. In this work, an efficient optimization strategy is proposed by co-modulating the dual anions (C and S) in Ni3C/Ni3S2, the heterostructured electrocatalyst, which is prepared via a simple hot-injection method. The presence of Ni3C/Ni3S2 heterojunctions accelerates the charge carrier transfer and promotes the generation of active sites, enabling the heterostructured electrocatalyst to achieve current densities of 10/100 mA cm-2 at 1.37 V/1.53 V. The Faradaic efficiencies for formate production coupled with hydrogen evolution approach 100%, accompanied with a stability record of 350 h. Additionally, operando electrochemical impedance spectroscopy (EIS), in situ Raman spectroscopy, and density functional theory (DFT) calculations further demonstrate that the creation of Ni3C/Ni3S2 heterointerfaces originating from dual anions' (C and S) differentiation is effective in adjusting the d-band center of active Ni atoms, promoting the generation of active sites, as well as optimizing the adsorption and desorption of reaction intermediates. This dual anions co-modulation strategy to stable heterostructure provides a general route for constructing high-performance transition metal-based electrocatalysts.

Targeting histone methylation and demethylation for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide, facing increasing challenges in terms of prevention and treatment. The methylation of lysine and arginine residues on histone proteins is dynamically controlled by histone methyltransferases (HMTs) and histone demethylases (HDMs), regulating chromatin structure and gene transcription. Mutations, genetic translocations, and altered gene expression involving HMTs and HDMs are frequently observed in NAFLD. HMTs and HDMs are receiving increasing attention in regulating NALFD. Targeting specific HMTs and HDMs for drug development is becoming a new strategy for treating NAFLD. This review provides a comprehensive summary of the regulatory mechanism of histone methylation/demethylation in NAFLD. Additionally, we discuss the potential applications of HMTs and HDMs inhibitors in preventing NAFLD, which may provide a scientific basis for the treatment of NAFLD.

Prospective study of dual-phase 99mTc-MIBI SPECT/CT nomogram for differentiating non-small cell lung cancer from benign pulmonary lesions.

OBJECTIVES: To establish and validate a technetium 99m sestamibi (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) nomogram for predicting non-small cell lung cancer (NSCLC). Comparing the diagnostic performance of early and delayed SPECT/CT nomogram, and compare the diagnostic performance of SPECT/CT radiomics models with single SPECT and CT radiomics models. METHODS: This prospective study included 119 lesions (NSCLC: n = 92, benign pulmonary lesions: n = 27) from 103 patients (mean age: 59.68 ± 8.94 years). Patients underwent dual-phase 99mTc-MIBI SPECT/CT imaging. They were divided into the training (n = 83) and validation (n = 36) cohorts. Logistic regression, support vector machine, random forest, and light-gradient boosting machine were applied to train and determine the optimal machine learning model. Then, combining radiomics score and clinical factors, establish nomograms for diagnosing NSCLC. RESULT: CYFRA21-1 was selected for constructing the clinical model. In early imaging, the areas under the curve (AUCs) of the clinical model, radiomics model, and nomogram were 0.571, 0.830, and 0.875, respectively. The nomogram performed better than the clinical model and similarly to the radiomics model (P=0.020, P=0.216), and there are no statistically significant differences in the predictive performance between the radiomics model and the clinical model (P=0.103). In delayed imaging, the AUC was 0.643, 0.888, and 0.893, respectively. The predictive performance of the nomogram was superior compared to the clinical model and comparable to the radiomics model (P=0.042, P=0.480), and the radiomics model also demonstrated superior diagnostic performance compared to the clinical model (P=0.049). Compared to early SPECT/CT results, the AUC values of the nomogram and radiomics models in the delayed phase were higher, although no statistical differences were found (P=0.831, P=0.568). In delayed imaging, the AUC of the radiomics models for CT and SPECT was 0.696 and 0.768, respectively, SPECT/CT radiomics exhibited significant differences compared with CT and SPECT alone (P=0.042, P=0.038). CONCLUSION: Dual-phase 99mTc-MIBI SPECT/CT nomograms and radiomics models can effectively predict NSCLC, providing an economically and non-invasive imaging method for diagnosing NSCLC, moreover, these findings provide a basis for early diagnosis and treatment strategies in NSCLC patients. Delayed-phase SPECT/CT imaging may offer greater practical value than early-phase imaging for diagnosing NSCLC. However, this novel approach necessitates further validation in larger, multi-center cohorts. CLINICAL RELEVANCE: Radiomics nomogram based on SPECT/CT for discriminating NSCLC from benign lung lesions helps to aid early diagnosis and guide treatment. KEY POINTS: Nomograms, based on dual-phase SPECT/CT, was constructed to discriminate between non-small cell lung cancer and benign lesions. SPECT/CT radiomics model has better predictive performance than SPECT and CT radiomics model.

Bioinspired molecular catalysts with a unique tricopper architecture for highly efficient oxygen reduction reaction.

In situ growth of intertwined trinuclear copper complexes (nCu3) on a cellulose-derived carbon support (CMC) produced a high-performance electrocatalyst (CMC-nCu3) for the oxygen reduction reaction (ORR), which demonstrated superior performance in zinc-air batteries compared to a commercial Pt/C catalyst. This work highlights the importance of copper-based molecular catalysts with rich and intertwined tricopper structures for boosting both ORR activity and stability.

Enhancing Functional Properties and Protein Structure of Almond Protein Isolate Using High-Power Ultrasound Treatment.

The suitability of a given protein for use in food products depends heavily on characteristics such as foaming capacity, emulsifiability, and solubility, all of which are affected by the protein structure. Notably, protein structure, and thus characteristics related to food applications, can be altered by treatment with high-power ultrasound (HUS). Almonds are a promising source of high-quality vegetable protein for food products, but their physicochemical and functional properties remain largely unexplored, limiting their current applications in foods. Here, we tested the use of HUS on almond protein isolate (API) to determine the effects of this treatment on API functional properties. Aqueous almond protein suspensions were sonicated at varying power levels (200, 400, or 600 W) for two durations (15 or 30 min). The molecular structure, protein microstructure, solubility, and emulsifying and foaming properties of the resulting samples were then measured. The results showed that HUS treatment did not break API covalent bonds, but there were notable changes in the secondary protein structure composition, with the treated proteins showing a decrease in α-helices and ß-turns, and an increase in random coil structures as the result of protein unfolding. HUS treatment also increased the number of surface free sulfhydryl groups and decreased the intrinsic fluorescence intensity, indicating that the treatment also led to alterations in the tertiary protein structures. The particle size in aqueous suspensions was decreased in treated samples, indicating that HUS caused the dissociation of API aggregates. Finally, treated samples showed increased water solubility, emulsifying activity, emulsifying stability, foaming capacity, and foaming stability. This study demonstrated that HUS altered key physicochemical characteristics of API, improving critical functional properties including solubility and foaming and emulsifying capacities. This study also validated HUS as a safe and environmentally responsible tool for enhancing desirable functional characteristics of almond proteins, promoting their use in the food industry as a high-quality plant-based protein.

The additive effect of the triglyceride-glucose index and estimated glucose disposal rate on long-term mortality among individuals with and without diabetes: a population-based study.

BACKGROUND: The triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), which are calculated using different parameters, are widely used as markers of insulin resistance and are associated with cardiovascular diseases and prognosis. However, whether they have an additive effect on the risk of mortality remains unclear. This study aimed to explore whether the combined assessment of the TyG index and eGDR improved the prediction of long-term mortality in individuals with and without diabetes. METHODS: In this cross-sectional and cohort study, data were derived from the National Health and Nutrition Examination Survey (NHANES) 2001-2018, and death record information was obtained from the National Death Index. The associations of the TyG index and eGDR with all-cause and cardiovascular mortality were determined by multivariate Cox regression analysis and restricted cubic splines. RESULTS: Among the 17,787 individuals included in the analysis, there were 1946 (10.9%) all-cause deaths and 649 (3.6%) cardiovascular deaths during a median follow-up of 8.92 years. In individuals with diabetes, the restricted cubic spline curves for the associations of the TyG index and eGDR with mortality followed a J-shape and an L-shape, respectively. The risk of mortality significantly increased after the TyG index was > 9.04 (all-cause mortality) or > 9.30 (cardiovascular mortality), and after eGDR was < 4 mg/kg/min (both all-cause and cardiovascular mortality). In individuals without diabetes, the association between eGDR and mortality followed a negative linear relationship. However, there was no association between the TyG index and mortality. Compared with individuals in the low TyG and high eGDR group, those in the high TyG and low eGDR group (TyG > 9.04 and eGDR < 4) showed the highest risk for all-cause mortality (hazard ratio [HR] = 1.592, 95% confidence interval [CI] 1.284-1.975) and cardiovascular mortality (HR = 1.683, 95% CI 1.179-2.400) in the overall population. Similar results were observed in individuals with and without diabetes. CONCLUSIONS: There was a potential additive effect of the TyG index and eGDR on the risk of long-term mortality in individuals with and without diabetes, which provided additional information for prognostic prediction and contributed to improving risk stratification.

CircRNA Arf3 suppresses glomerular mesangial cell proliferation and fibrosis in diabetic nephropathy via miR-107-3p/Tmbim6 axis.

Diabetic nephropathy (DN) is one of microvascular complication associated with diabetes. Circular RNAs (circRNAs) have been shown to be involved in DN pathogenesis. Hence, this work aimed to explore the role and mechanism of circ_Arf3 in DN. Mouse mesangial cells (MCs) cultured in high glucose (HG) condition were used for functional analysis. Cell proliferation was determined using 5-ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 assays. Western blotting was used to measure the levels of proliferation indicator PCNA and fibrosis-related proteins α-smooth muscle actin (α-SMA), collagen I (Col I), fibronectin (FN), and collagen IV (Col IV). The binding interaction between miR-107-3p and circ_Arf3 or Tmbim6 (transmembrane BAX inhibitor motif containing 6) was confirmed using dual-luciferase reporter and pull-down assays. Circ_Arf3 is a stable circRNA, and the expression of circ_Arf3 was decreased after HG treatment in MCs. Functionally, ectopic overexpression of circ_Arf3 protected against HG-induced proliferation and elevation of fibrosis-related proteins in MCs. Mechanistically, circ_Arf3 directly bound to miR-107-3p, and Tmbim6 was a target of miR-107-3p. Further rescue assay showed miR-107-3p reversed the protective action of circ_Arf3 on MCs function under HG condition. Moreover, inhibition of miR-107-3p suppressed HG-induced proliferation and fibrosis, which were attenuated by Tmbim6 knockdown in MCs. CircRNA Arf3 could suppress HG-evoked mesangial cell proliferation and fibrosis via miR-107-3p/Tmbim6 axis, indicating the potential involvement of this axis in DN progression.

The cost of total hip arthroplasty: compare the hospitalization costs of national centralized procurement and national volume-based procurement.

Background: With the increasing demand for joint replacement surgery in China, the government has successively issued the policies of national centralized procurement (NCP) and national volume-based procurement (NVBP) of artificial joints. The purpose of this study is to evaluate the impact of NCP and NVBP policies on hospitalization cost, rehospitalization and reoperation rate of total hip arthroplasty (THA). Methods: In total, 347 patients who underwent THA from January 2019 to September 2022 were retrospectively analyzed. According to the implementation of NCP and NVBP, patients were divided into three groups: control group (n = 147), NCP group (n = 130), and NVBP group (n = 70). Patient-level data on the total hospitalization costs, rehospitalization rate, THA reoperation rate and inpatient component costs were collected before and after the implementation of the policies and Consumer Price Index was used to standardize the cost. Results: After the implementation of NCP and NVBP, the total cost of hospitalization decreased by $817.41 and $3950.60 (p < 0.01), respectively. The implantation costs decreased from $5264.29 to $4185.53 and then rapidly to $1143.49 (p < 0.01), contributing to increased total cost savings. However, the cost of surgery and rehabilitation increased after NCP and NVBP implementation (p < 0.01). The proportion of implants decreased from 66.76 to 59.22% and then to 29.07%, whereas that of drugs increased from 7.98 to 10.11% and then to 12.06%. The proportion of operating expenses rose from 4.86 to 8.01% and then to 18.47%. Univariate linear regression analysis showed that hospital stay, NCP and NVBP were correlated with total hospitalization cost (p < 0.01). Multivariate analysis showed that hospital stay, NCP and NVBP were independent predictors of total hospitalization cost (p < 0.01). Conclusion: In this study, hospital stay, NCP, and NVBP were independent predictors of total inpatient costs. After the implementation of NVBP policy, the cost of implants and hospitalization has decreased significantly, and the technical labor value of medical staff has increased, but a multifaceted method is still needed to solve the problem of increasing costs of other consumables. Limitations of the study suggest the need for further and more comprehensive evaluation in the future.

Targeting DNA methyltransferases for cancer therapy.

DNA methyltransferases (DNMTs) play a crucial role in genomic DNA methylation. In mammals, DNMTs regulate the dynamic patterns of DNA methylation in embryonic and adult cells. Abnormal functions of DNMTs are often indicative of cancers, including overall hypomethylation and partial hypermethylation of tumor suppressor genes (TSG), which accelerate the malignancy of tumors, worsen the condition of patients, and significantly exacerbate the difficulty of cancer treatment. Currently, nucleoside DNMT inhibitors such as Azacytidine and Decitabine have been approved by the FDA and EMA for the treatment of acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelodysplastic syndrome (MDS). Therefore, targeting DNMTs is a very promising anti-tumor strategy. This review mainly summarizes the therapeutic effects of DNMT inhibitors on cancers. It aims to provide more possibilities for the treatment of cancers by discovering more DNMT inhibitors with high activity, high selectivity, and good drug-like properties in the future.

Creating Asymmetric Fe-N3C-N Sites in Single-Atom Catalysts Boosts Catalytic Performance for Oxygen Reduction Reaction.

Fine tuning of the metal site coordination environment of a single-atom catalyst (SAC) to boost its catalytic activity for oxygen reduction reaction (ORR) is of significance but challenging. Herein, we report a new SAC bearing Fe-N3C-N sites with asymmetric in-plane coordinated Fe-N3C and axial coordinated N atom for ORR, which was obtained by pyrolysis of an iron isoporphyrin on polyvinylimidazole (PVI) coated carbon black. The C@PVI-(NCTPP)Fe-800 catalyst exhibited significantly improved ORR activity (E1/2 = 0.89 V vs RHE) than the counterpart SAC with Fe-N4-N sites in 0.1 M KOH. Significantly, the Zn-air batteries equipped with the C@PVI-(NCTPP)Fe-800 catalyst demonstrated an open-circuit voltage (OCV) of 1.45 V and a peak power density (Pmax) of 130 mW/cm2, outperforming the commercial Pt/C catalyst (OCV = 1.42 V; Pmax = 119 mW/cm2). The density functional theory (DFT) calculations revealed that the d-band center of the asymmetric Fe-N3C-N structure shifted upward, which enhances its electron-donating ability, favors O2 adsorption, and supports O-O bond activation, thus leading to significantly promoted catalytic activity. This research presents an intriguing strategy for the designing of the active site architecture in metal SACs with a structure-function controlled approach, significantly enhancing their catalytic efficiency for the ORR and offering promising prospects in energy-conversion technologies.

Melatonin Ameliorates Depressive-Like Behaviors in Ovariectomized Mice by Improving Tryptophan Metabolism via Inhibition of Gut Microbe Alistipes Inops.

Melatonin (N-acetyl-5-methoxytryptamine) is reported to improve mood disorders in perimenopausal women and gut microbiome composition is altered during menopausal period. The possible role of microbiome in the treatment effect of melatonin on menopausal depression remains unknown. Here, it is shown that melatonin treatment reverses the gut microbiota dysbiosis and depressive-like behaviors in ovariectomy (OVX) operated mice. This effect of melatonin is prevented by antibiotic cocktails (ABX) treatment. Transferring microbiota harvested from adolescent female mice to OVX-operated mice is sufficient to ameliorate depressive-like behaviors. Conversely, microbiota transplantation from OVX-operated mice or melatonin-treated OVX-operated mice to naïve recipient mice exhibits similar phenotypes to donors. The colonization of Alistipes Inops, which is abundant in OVX-operated mice, confers the recipient with depressive-like behaviors. Further investigation indicates that the expansion of Alistipes Inops induced by OVX leads to the degradation of intestinal tryptophan, which destroys systemic tryptophan availability. Melatonin supplementation restores systemic tryptophan metabolic disorders by suppressing the growth of Alistipes Inops, which ameliorates depressive-like behaviors. These results highlight the previously unrecognized role of Alistipes Inops in the modulation of OVX-induced behavioral disorders and suggest that the application of melatonin to inhibit Alistipes Inops may serve as a potential strategy for preventing menopausal depressive symptoms.

The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes: findings from a prospective, nationwide, and multicenter registry.

OBJECTIVES: To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS: We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542-5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041-6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS: This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI.

An overview of cyclopropenone derivatives as promising bioactive molecules.

Cyclopropenone is a valuable electrophilic reagent that can react with electrophilic reagents, nucleophilic reagents, free radicals, organic metals, etc. Furthermore, cyclopropenone derivatives have shown significant biological activity in various diseases, such as triple-negative breast cancer (TNBC), melanoma, and alopecia areata (AA). The cyclopropenone analogue diphenylcyclopropenone (DPCP) has been approved for the treatment of AA. Given the potential therapeutic benefits of cyclopropenone derivatives, this review aims to systematically summarize the structures, synthesis routes, and potential pharmacological functions of cyclopropenone analogues in the hope of offering novel insights for further rational design of more drugs based on the cyclopropenone skeleton for the treatment of human diseases.

Enhancing oxygen reduction activity of dinuclear copper complexes loaded on an N-doped carbon support via a low-temperature pyrolysis strategy.

Bioinspired by the active sites of multicopper oxidases (MCOs), bi/multinuclear copper complexes have attracted great attention in promoting catalytic activity for the oxygen reduction reaction (ORR). Herein, we report the preparation of a Cu-N-C electrocatalyst Cu-BPOZ@CNB-400 for efficient ORR, which was obtained by low temperature pyrolysis of a dinuclear 2,5-bis(2-pyridyl)-1,3,4-oxadiazole (BPOZ) copper complex loaded on a N-doped carbon support at 400 °C. Cu-BPOZ@CNB-400 exhibited a half-wave potential (E1/2) of 0.86 V vs. RHE for the ORR in 0.1 M KOH solution, which was significantly higher than that of the Cu-BPOZ@CNB-800 (E1/2 = 0.83 V) catalyst treated under high temperature (at 800 °C) and the control catalyst Cu-Phen@CNB-400 (E1/2 = 0.82 V) derived from low-temperature-treatment (at 400 °C) of a mononuclear phenanthroline-coordinated-Cu complex loaded on a N-doped carbon support. When Cu-BPOZ@CNB-400 was applied as the cathode catalyst in zinc-air batteries a maximum power density (Pmax) of 127 mW cm-2 could be achieved, demonstrating comparable catalyst performance to the commercial 20 wt% Pt/C (Pmax = 122 mW cm-2) and the control Cu-Phen@CNB-400 catalyst (Pmax = 105 mW cm-2) under similar experimental conditions. Low-temperature pyrolysis of dinuclear copper complexes on a carbon support improved the charge transfer efficiency, inhibited metal aggregation, and could produce highly dispersed Cu-N-C catalysts with dinuclear copper sites for promoting the 4e--reduction selectivity of the ORR. It thus provides a cost-effective approach for the controllable fabrication of efficient ORR catalysts to be applied for energy conversion devices.

Integrated 68 Ga-FAPI-04 PET/MR in Pancreatic Cancer : Prediction of Tumor Response and Tumor Resectability After Neoadjuvant Therapy.

PURPOSE: This study aimed to investigate the value of 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/MR semiquantitative parameters in the prediction of tumor response and resectability after neoadjuvant therapy in patients with pancreatic cancer. PATIENTS AND METHODS: This study was performed retrospectively in patients with borderline resectable or locally advanced pancreatic cancer who underwent 68 Ga-FAPI PET/MRI from June 2020 to June 2022. The SUV max , SUV mean , SUV peak , uptake tumor volume (UTV), and total lesion FAP expression (TLF) of the primary tumor were recorded. The target-to-background ratios (TBRs) of the primary tumor to normal tissue muscle (TBR muscle ) and blood (TBR blood ) were also calculated. In addition, the minimum apparent diffusion coefficient value of the tumor was measured. After 3-4 cycles of gemcitabine + nab-paclitaxel chemotherapy, patients were divided into responders and nonresponders groups according to RECIST criteria (v.1.1). They were also divided into resectable and unresectable groups according to the surgical outcome. The variables were compared separately between groups. RESULTS: A total of 18 patients who met the criteria were included in this study. The UTV and TLF were significantly higher in nonresponders than in responders ( P < 0.05). The SUV max , SUV mean , and TBR muscle were significantly higher in unresectable patients than in resectable ones ( P < 0.05). Receiver operating characteristic curve analysis identified UTV (area under the curve [AUC] = 0.840, P = 0.015) and TLF (AUC = 0.877, P = 0.007) as significant predictors for the response to gemcitabine + nab-paclitaxel chemotherapy, with cutoff values of 25.05 and 167.38, respectively. In addition, SUV max (AUC = 0.838, P = 0.016), SUV mean (AUC = 0.812, P = 0.026), and TBR muscle (AUC = 0.787, P = 0.041) were significant predictors of the resectability post-NCT, with cutoff values of 14.0, 6.0, and 13.9, respectively. According to logistic regression analysis, TLF was found to be significantly associated with tumor response ( P = 0.032) and was an independent predictor of tumor response ( P = 0.032). In addition, apparent diffusion coefficient value was an independent predictor of tumor resectability ( P = 0.043). CONCLUSIONS: This pilot study demonstrates the value of 68 Ga-FAPI PET/MR for the prediction of tumor response and resectability after neoadjuvant therapy. It may aid in individualized patient management by guiding the treatment regimens.

A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice.

Asthma, the most prevalent respiratory disease, affects more than 300 million people and causes more than 250,000 deaths annually. Type 2-high asthma is characterized by interleukin (IL)-5-driven eosinophilia, along with airway inflammation and remodeling caused by IL-4 and IL-13. Here we utilize IL-5 as the targeting domain and deplete BCOR and ZC3H12A to engineer long-lived chimeric antigen receptor (CAR) T cells that can eradicate eosinophils. We call these cells immortal-like and functional IL-5 CAR T cells (5TIF) cells. 5TIF cells were further modified to secrete an IL-4 mutein that blocks IL-4 and IL-13 signaling, designated as 5TIF4 cells. In asthma models, a single infusion of 5TIF4 cells in fully immunocompetent mice, without any conditioning regimen, led to sustained repression of lung inflammation and alleviation of asthmatic symptoms. These data show that asthma, a common chronic disease, can be pushed into long-term remission with a single dose of long-lived CAR T cells.

Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated. METHODS: We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (three each from CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. RESULTS: Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. CONCLUSIONS: Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

A cyclic nucleotide-gated channel gene HcCNGC21 positively regulates salt and drought stress responses in kenaf (Hibiscus cannabinus L.).

Cyclic Nucleotide-Gated Channels (CNGCs) serve as Ca2+ permeable cation transport pathways, which are involved in the regulation of various biological functions such as plant cell ion selective permeability, growth and development, responses to biotic and abiotic stresses. At the present study, a total of 31 CNGC genes were identified and bioinformatically analyzed in kenaf. Among these genes, HcCNGC21 characterized to localize at the plasma membrane, with the highest expression levels in leaves, followed by roots. In addition, HcCNGC21 could be significantly induced under salt or drought stress. Virus-induced gene silencing (VIGS) of HcCNGC21 in kenaf caused notable growth inhibition under salt or drought stress, characterized by reductions in plant height, stem diameter, leaf area, root length, root surface area, and root tip number. Meanwhile, the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were significantly decreased, accompanied by reduced levels of osmoregulatory substances and total chlorophyll content. However, ROS accumulation and Na+ content increased. The expression of stress-responsive genes, such as HcSOD, HcPOD, HcCAT, HcERF3, HcNAC29, HcP5CS, HcLTP, and HcNCED, was significantly downregulated in these silenced lines. However, under salt or drought stress, the physiological performance and expression of stress-related genes in transgenic Arabidopsis thaliana plants overexpressing HcCNGC21 were diametrically opposite to those of TRV2-HcCNGC21 kenaf line. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays revealed that HcCNGC21 interacts with HcAnnexin D1. These findings collectively underscore the positive role of HcCNGC21 in plant resistance to salt and drought stress.

Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury.

Mild traumatic brain injury (mTBI)-induced post-traumatic headache (PTH) is a pressing public health concern and leading cause of disability worldwide. Although PTH is often accompanied by neurological disorders, the exact underlying mechanism remains largely unknown. Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH. In this study, a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery. Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage. Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum, temporal lobe/cortex, and hippocampal regions during the early stages of PTH. Additionally, variations in brain functional activities and connectivity were further detected in the early stage of PTH, particularly in the cerebellum and temporal cortex, suggesting that these regions play central roles in the mechanism underlying PTH. Moreover, our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH. Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex, with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.