Engineered droplet-forming peptide as photocontrollable phase modulator for fused in sarcoma protein.

The assembly and disassembly of biomolecular condensates are crucial for the subcellular compartmentalization of biomolecules in the control of cellular reactions. Recently, a correlation has been discovered between the phase transition of condensates and their maturation (aggregation) process in diseases. Therefore, modulating the phase of condensates to unravel the roles of condensation has become a matter of interest. Here, we create a peptide-based phase modulator, JSF1, which forms droplets in the dark and transforms into amyloid-like fibrils upon photoinitiation, as evidenced by their distinctive nanomechanical and dynamic properties. JSF1 is found to effectively enhance the condensation of purified fused in sarcoma (FUS) protein and, upon light exposure, induce its fibrilization. We also use JSF1 to modulate the biophysical states of FUS condensates in live cells and elucidate the relationship between FUS phase transition and FUS proteinopathy, thereby shedding light on the effect of protein phase transition on cellular function and malfunction.

A Rare Case of Follicular Dendritic Cell Tumor of the Abdominal Cavity Visualized by 18F-AlF-NOTA-Octreotide PET/CT.

ABSTRACT: Positivity of follicular dendritic cell tumor in somatostatin receptor imaging is rare. A 68-year-old woman underwent ultrasound in health examination. The results showed abnormal echoes in the pancreatic head region, suggestive of a neuroendocrine tumor of the pancreatic head. 18F-AlF-NOTA-octreotide PET/CT was performed for staging. 18F-AlF-NOTA-octreotide PET/CT revealed an irregular mass between the caudate lobe of the liver and the pancreatic head with heterogeneously increased uptake, which was later confirmed as follicular dendritic cell tumor by pathological examination.

Diagnostic performance and clinical impact of 18F-AlF-NOTA-octreotide in a large cohort of patients with neuroendocrine neoplasms: A prospective single-center study.

Purpose: Somatostatin receptor imaging with 18F-AlF-NOTA-octreotide (18F-AlF-OC) has shown promising performance in neuroendocrine neoplasms (NENs). In this study, we aim to investigate the diagnostic performance and clinical impact of 18F-AlF-OC in a large prospective cohort of patients with NEN. Methods: Between January 2023 and November 2023, a total of 219 patients with confirmed or suspected NEN were enrolled prospectively and underwent 18F-AlF-OC PET/CT at 2 h post-injection. The primary endpoint was the diagnostic performance, including sensitivity, specificity, and accuracy. An additional primary endpoint was the impact of 18F-AlF-OC on clinical management. The reference standard was based on the results of histopathology or radiological follow-up. Results: 205 patients were included in the final analysis. The patient-level sensitivity, specificity, and accuracy of 18F-AlF-OC PET/CT compared with contrast-enhanced CT/MRI were 90.5% vs. 81.8%, 93.1% vs. 71.1%, and 91.2% vs. 79.4%, respectively. 26 patients had tiny gastrointestinal NENs (smaller than 1 cm in diameter). The patient-based sensitivity of 18F-AlF-OC PET/CT and contrast-enhanced CT/MRI were 61.5% (16/26) and 37.5% (9/24), respectively. The smallest diameter of gastrointestinal NEN detected by 18F-AlF-OC PET/CT was 0.6 cm in the rectum, 0.3 cm in the stomach, and 0.5 cm in the duodenum. 18F-AlF-OC PET/CT results led to changes in clinical management in 19.5% of patients (40/205), owing mainly to new or unexpected findings compared to contrast-enhanced CT/MRI. Conclusion: 18F-AlF-OC PET/CT demonstrated great diagnostic performance in patients with NEN, particularly for detecting tiny gastrointestinal NEN. Furthermore, 18F-AlF-OC PET/CT impacted the therapeutic management in 19.5% of patients. Our results further validate the role of 18F-AlF-OC as a somatostatin receptor imaging tracer in clinical practice.

Relationships Among Serological Indicators and In Vitro High-Throughput Drug Sensitivity Screening Results in Patients with Hepatocellular Carcinoma.

AIM: The purpose of this study was to analyze the relationship between serum indicators and high-throughput drug screening (HDS) results, aiming to achieve specific therapy for hepatocellular carcinoma (HCC). METHODS: This study recruited patients with HCC who underwent surgical resection at the Hepatobiliary Surgery Center of the First Affiliated Hospital of Chongqing Medical University from December 2019 to December 2021. HCC tissues were obtained from patients during surgery and subjected to in vitro cell culture, and then HDS testing was performed on the cultured tissue samples. We used Spearman's correlation analysis to examine the relationships between drug sensitivity results for anti-hepatocellular carcinoma drugs, other antitumor drugs, and serological indicators, the Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), Prognostic Nutritional Index (PNI), and Lymphocyte Monocyte Ratio (LMR). A significant correlation was considered when P<0.05 and |r|>0.40. Furthermore, linear regression analysis was conducted to elucidate the relationship between serological indicators and drug susceptibility, with significant results indicated by P<0.05 and R²≥0.50. RESULTS: In this study, 82 patients with HCC who had undergone hepatectomy and completed in vitro cell culture and HDS testing were evaluated. Using Spearman's correlation with a significance threshold of P<0.05 and |r|>0.40, we identified significant associations between serological indicators and specific drug regimens: NLR correlated with 5-Fluorouracil, 5- Fluorouracil+Calcium folinate (FOLFOX4), and Capecitabine + Cisplatin (XP); PLR with FOLFOX4; SII with XP, FOLFOX4, Doxorubicin + Oxaliplatin (ADM+L-OHP); and SIRI with XP and FOLFOX4. No correlations were found between PNI or LMR and any drug inhibition rates. A comprehensive evaluation using linear regression analysis-which included variables such as sex, age, hepatitis B virus and liver cirrhosis status, size and number of lesions, alphafetoprotein, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, and prothrombin time, alongside NLR, PLR, SII, and SIRI was conducted in relation to drug regimens. This analysis revealed that NLR, SII, and SIRI are significant predictors of FOLFOX4 inhibition rate, while NLR predicts the inhibition rate of XP effectively. However, no significant links were established between molecular targeted drugs, other antitumor drugs, and serological indicators. CONCLUSIONS: NLR, SII, and SIRI were correlated with FOLFOX4, and the higher the values of NLR, SII, and SIRI, the higher the in vitro inhibition of FOLFOX. Also, NLR was correlated with XP, and the higher the value of NLR, the higher the in vitro inhibition of XP.

Efficacy and safety of percutaneous transhepatic biliary radiofrequency ablation in patients with malignant obstructive jaundice.

BACKGROUND: Percutaneous transhepatic cholangiodrainage (PTCD) and endoscopic retrograde cholangiopancreatography/endoscopic nasobiliary drainage are the most common clinical procedures for jaundice control in patients with unresectable malignant obstructive jaundice, yet the safety and effect of endobiliary radiofrequency ablation (EB-RFA) combined PTCD is rarely reported, in this article, we report our experience of EB-RFA combined PTCD in such patients. AIM: To retrospectively study the efficacy and safety of EB-RFA combined PTCD in patients with unresectable malignant obstructive jaundice. METHODS: Patients with unresectable malignant obstructive jaundice treated with EB-RFA under PTCD were selected, the bile ducts of the right posterior lobe was selected as the target bile ducts in all cases. The general conditions of all patients, preoperative tumour markers, total bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB), alkaline phosphatase (ALP), and glutamyl transferase (GGT) before and on the 7th day after the procedure, as well as perioperative complications, stent patency time and patient survival were recorded. RESULTS: All patients successfully completed the operation, TBIL and DBIL decreased significantly in all patients at the 7th postoperative day (P = 0.009 and 0.006, respectively); the values of ALB, ALP and GGT also decreased compared with the preoperative period, but the difference was not statistically significant. Perioperative biliary bleeding occurred in 2 patients, which was improved after transfusion of blood and other conservative treatments, pancreatitis appeared in 1 patient after the operation, no serious complication and death happened after operation. Except for 3 patients with loss of visits, the stent patency rate of the remaining 14 patients was 100% 71% and 29% at the 1st, 3rd, and 6th postoperative months respectively, with a median survival of 4 months. CONCLUSION: EB-RFA under PTCD in patients with unresectable malignant obstructive jaundice has a satisfactory therapeutic effect and high safety, which is worthy of further clinical practice.

A Population-Based Tumor-Volume Model for Head and Neck Cancer During Radiation Therapy With a Dynamic Oxygenated Compartment.

PURPOSE: With the coming era of digital medicine and healthcare technology, mathematical modeling of tumors has become a key step to optimize and realize precision radiation therapy. The purpose of this study was to develop a mathematical model for simulating the change of head and neck (HN) tumor volume during radiation therapy. METHODS AND MATERIALS: A formula was developed to describe the dynamic change of oxygenated compartment within a tumor, which was combined with the lethal lesions model to describe various cell processes during radiation therapy, including potentially lethal lesion repair and misrepair, cell proliferation/loss, and tumor reoxygenation. Parameter sensitivity analysis was performed to evaluate the impacts of lesion- and repair-related biological factors on radiation therapy outcomes. RESULTS: We tested our model on 14 available patients with HN cancer and compared the performance with 3 other models. The mean error of our model for the 12 good fit cases was 12.2%, which is considerably smaller than that of the linear quadratic model (19.7%), the generalized linear quadratic model (19.1%), and a 4-level cell population model (16.6%). Correlation analysis results revealed that for small tumors, there was a positive correlation (correlation coefficient r=0.9416) between hypoxic fraction (hf) and tumor volume, whereas the correlation became negative and not significant (r=-0.4365) for large tumors. It is demonstrated from sensitivity analysis that the production rate of lethal lesions (ηl) has a far greater impact on tumor volume than other parameters. The hf had an insignificant impact on tumor volume but had a notable influence on the volume of surviving cells. The final volume of surviving cells athf=0.5 was almost 8 ×102 times that of hf=0.01. The potentially lethal lesion-related parameters (the production rate of potentially lethal lessions per unit dose ηpl, the rate of correct repair per unit time εpl, and the rate of binary misrepair per unit time ε2pl) had rather small impacts (<1%) on both tumor volume and the volume of surviving cells, which indicates that the repaired and misrepaired sublethal cells only take up a small portion of the total cancer cell population. CONCLUSIONS: A population-based tumor-volume model for HN cancer during radiation therapy with a dynamic oxygenated compartment was developed in this study. Comprehensively considering the damage process of tumor cells caused by radiation therapy, the accurate prediction of the volume change of HN tumors during treatment was revealed. Meanwhile, various cell activities and their principles in the process of antitumor treatment were reflected, which has positive clinical reference significance for radiobiology.

Chlorin e6 and BLZ945 Based Self-Assembly for Photodynamic Immunotherapy Through Immunogenic Tumor Induction and Tumor-Associated Macrophage Depletion.

Immunotherapeutic effect is restricted by the nonimmunogenic tumor phenotype and immunosuppression behaviors of tumor-associated macrophages (TAMs). In this work, a drug self-assembly (designated as CeBLZ) is fabricated based on chlorin e6 (Ce6) and BLZ945 to activate photodynamic immunotherapy through tumor immunogenic induction and tumor-associated macrophage depletion. It is found that Ce6 tends to assemble with BLZ945 without any drug excipients, which can enhance the cellular uptake, tumor penetration, and blood circulation behaviors. The robust photodynamic therapy effect of CeBLZ efficiently suppresses the primary tumor growth and also triggers immunogenic cell death to reverse the nonimmunogenic tumor phenotype. Moreover, CeBLZ can deplete TAMs in tumor tissues to reverse the immunosuppression microenvironment, activating abscopal effect for distant tumor inhibition. In vitro and in vivo results confirm the superior antitumor effect of CeBLZ with negligible side effect, which might promote the development of sophisticated drug combinations for systematic tumor management.

Analysis of the Parotid Glands on an Energy Spectrum CT Iodine Map to Evaluate Irradiation-Induced Acute Xerostomia in Patients With Nasopharyngeal Carcinoma.

Objective: This prospective study aims to evaluate acute irradiation-induced xerostomia during radiotherapy by utilizing the normalized iodine concentration (NIC) derived from energy spectrum computed tomography (CT) iodine maps. Methods: In this prospective study, we evaluated 28 patients diagnosed with nasopharyngeal carcinoma. At 4 distinct stages of radiotherapy (0, 10, 20, and 30 fractions), each patient underwent CT scans to generate iodine maps. The NIC of both the left and right parotid glands was obtained, with the NIC at the 0-fraction stage serving as the baseline measurement. After statistically comparing the NIC obtained in the arterial phase, early venous phase, late venous phase, and delayed phase, we chose the late venous iodine concentration as the NIC and proceeded to analyze the variations in NIC at each radiotherapy interval. Using the series of NIC values, we conducted hypothesis tests to evaluate the extent of change in NIC within the parotid gland across different stages. Furthermore, we identified the specific time point at which the NIC decay exhibited the most statistically significant results. In addition, we evaluated the xerostomia grades of the patients at these 4 stages, following the radiation therapy oncology group (RTOG) xerostomia evaluation standard, to draw comparisons with the changes observed in NIC. Results: The NIC in the late venous phase exhibited the highest level of statistical significance (P < .001). There was a noticeable attenuation in NIC as the RTOG dry mouth grade increased. Particularly, at the 20 fraction, the NIC experienced the most substantial attenuation (P < .001), a significant negative correlation was observed between the NIC of the left, right, and both parotid glands, and the RTOG evaluation grade of acute irradiation-induced xerostomia (P < .001, r = -0.46; P < .001, r = -0.45; P < .001, r = -0.47). The critical NIC values for the left, right, and both parotid glands when acute xerostomia occurred were 0.175, 0.185, and 0.345 mg/ml, respectively, with AUC = 0.73, AUC = 0.75, and AUC = 0.75. Conclusion: The NIC may be used to evaluate changes in parotid gland function during radiotherapy and acute irradiation-induced xerostomia.

hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing.

RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites. hnRNPM preferentially binds at intronic LINEs to repress pseudo splice site usage for cryptic splicing. Remarkably, cryptic exons can generate long dsRNAs through base-pairing of inverted ALU transposable elements interspersed among LINEs and consequently trigger an interferon response, a well-known antiviral defense mechanism. Significantly, hnRNPM-deficient tumors show upregulated interferon-associated pathways and elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity by repressing cryptic splicing and suggest that targeting hnRNPM in tumors may be used to trigger an inflammatory immune response, thereby boosting cancer surveillance.

How does the e-cigarette industry respond to tax adjustments? Evidence from China.

INTRODUCTION: China enacted an excise tax on e-cigarettes in November 2022, which offers a distinctive opportunity to examine the industry's reactions to this fiscal adjustment. This study delves into the industry's pricing strategies following the introduction of the excise tax, facilitating a thorough assessment of the subsequent impact on market dynamics and the government's revenue streams. METHODS: We developed a TaXSiM model specifically tailored for e-cigarettes in China by integrating the country's e-cigarette tax framework. Our approach involved leveraging market data obtained from a representative product, the RELX Phantom Series, to ensure the model's effectiveness and relevance. RESULTS: The excise implementation of 2022 significantly heightened the tax burden on e-cigarettes, marking an increase of approximately 150 RMB per device and 19 RMB per cartridge. Despite these financial pressures, electronic cigarette firms exemplified by RELX, strategically endeavored to sustain competitiveness. Their approach involved initially implementing a 'Razor blade model' and eventually a 'comprehensive under-shifting' strategy, which mitigated the health impact of the tax hike, resulting in a relatively minor decline in sales while amplifying the impact on tax revenue. However, this strategic pricing maneuver came at a cost, as it led to a substantial decrease in profits, and therefore expedited a reshuffling of the industry by compelling smaller brands to leave the market rapidly. CONCLUSIONS: To effectively curb the use of e-cigarettes through tax policies, it is advisable to relocate the imposition of excise taxes on electronic cigarettes to the retail stage. This shift aims to narrow the scope for industry-level pricing strategies. Furthermore, this approach should be coupled with the introduction of an additional specific tax, strategically crafted to accentuate the health-related benefits associated with the excise taxation on electronic cigarettes.

Intracellular Criegee's mechanism-based synergistic ozone therapy mediated by oleogels for cancer treatment.

Broad cellular components-initiated efficient chemical reactions that occur in malignant cells may contribute to exploring emerging strategies for cancer treatment. Herein, an ozonated oleogel (OG(O)) was developed to achieve cancer ozone therapy (O3-T) based on intracellular Criegee's reaction. By integrating the chemo-drug, the ozone-loaded oleogel (Dox@OG(O)) was prepared as a chemotherapeutic agent for local O3-T, associated with chemotherapy (CT)/radiotherapy (RT)/immunotherapy and wound healing. The in vitro results showed that, Dox@OG(O) could achieve high ozone loading efficiency and ensure its stability. This Oleogel-mediated O3-T could directly destroy tumor cells via intracellular Criegee's reaction occurred on cell membranes, as well as the effects of tumor microenvironment (TME) regulation by the generation of oxygen/reactive oxygen species (ROS) and depletion of glutathione (GSH). Meanwhile, under the stimulation of X-ray, an accelerated free radical's production was observed, further combined with the radio-sensitivity after TME regulation, an effective anti-tumor effect would be achieved. Further on, in vivo results demonstrated that the locally implanted Dox@OG(O) could effectively inhibit the growth of both primary and secondary tumors. Considering these results above, it will serve as inspiration for future studies investigating of O3-T, especially for postoperative skin diseases.

Impact of chrono-radiotherapy on the prognosis and treatment-related toxicity in patients with locally advanced nasopharyngeal carcinoma: A multicenter propensity-matched study.

The timing of radiotherapy (RT) delivery has been reported to affect both cancer survival and treatment toxicity. However, the association among the timing of RT delivery, survival, and toxicity in locally advanced nasopharyngeal carcinoma (LA-NPC) has not been investigated. We retrospectively reviewed patients diagnosed with LA-NPC who received definitive RT at multiple institutions. The median RT delivery daytime was categorized as morning (DAY) and night (NIGHT). Seasonal variations were classified into the darker half of the year (WINTER) and brighter half (SUMMER) according to the sunshine duration. Cohorts were balanced according to baseline characteristics using propensity score matching (PSM). Survival and toxicity outcomes were evaluated using Cox regression models. A total of 355 patients were included, with 194/161 in DAY/NIGHT and 187/168 in WINTER/SUMMER groups. RT delivered during the daytime prolonged the 5-year overall survival (OS) (90.6% vs. 80.0%, p = 0.009). However, the significance of the trend was lost after PSM (p = 0.068). After PSM analysis, the DAY cohort derived a greater benefit in 5-year progression-free survival (PFS) (85.6% vs. 73.4%, p = 0.021) and distant metastasis-free survival (DMFS) (89.2% vs. 80.8%, p = 0.051) in comparison with the NIGHT subgroup. Moreover, multivariate analysis showed that daytime RT was an independent prognostic factor for OS, PFS, and DMFS. Furthermore, daytime RT delivery was associated with an increase in the incidence of leukopenia and radiation dermatitis. RT delivery in SUMMER influenced only the OS significantly (before PSM: p = 0.051; after PSM: p = 0.034). There was no association between toxicity and the timing of RT delivery by season. In LA-NPC, the daytime of radical RT served as an independent prognostic factor. Furthermore, RT administered in the morning resulted in more severe toxic side effects than that at night, which needs to be confirmed in a future study.

Frailty and Health-Related Quality of Life in Elderly Patients Undergoing Esophageal Cancer Surgery: A Longitudinal Study.

PURPOSE: This study aims to elucidate the longitudinal alterations in frailty and health-related quality of life experienced by elderly patients undergoing surgical treatment for esophageal cancer. Additionally, it seeks to ascertain the impact of preoperative frailty on postoperative health-related quality of life over time. METHODS: 131 patients were included in the prospective study. Patients' frailty and health-related quality-of-life were assessed utilizing the Tilburg and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at preoperative, 1 week, 1 month, and 3 months, postoperatively. Statistical analyses were performed using generalized estimating equations, repeated-measures analysis of variance, and linear mixed models (LMMs). RESULTS: Out of 131 patients, 28.2% had frailty before surgery, and the prevalence of frailty consistently higher after surgery compared with baseline (67.9%, 51.9%, and 39.7%). There was no significant change in frailty scores in preoperative frail patients within 3 months following surgery (p = .496, p < .999, p < .999); whereas in preoperative non-frail patients, the frailty scores increased at 1 week (p < .001) and then decreased at 1 month (p = .014), followed by no change at 3 months. In addition, preoperative frail patients had significantly worse global quality-of-life (ß = -4.24 (-8.31; -.18), p = .041), physical functioning (ß = -9.87 (-14.59; -5.16), p < .001), role functioning (ß = -10.04 (-15.76; -4.33), p = .001), and social functioning (ß = -8.58 (-15.49; -1.68), p = .015), compared with non-frail patients. CONCLUSIONS: A significant proportion of participants exhibited a high prevalence of preoperative frailty. These patients, who were preoperatively frail, exhibited a marked reduction in health-related quality-of-life, a more gradual recovery across various functional domains, and an increased symptom burden during the follow-up period. Therefore, it is crucial to meticulously identify and closely monitor patients with preoperative frailty for any changes in their postoperative physiology, role, and social functioning.

Do tougher drinking policies affect men's smoking behavior - Evidence from China.

In 2011, China implemented tougher driving-under-the-influence laws, which criminalized driving under the influence of alcohol for the first time and increased penalties. This paper provides the first comprehensive analysis of the effects of stricter drinking policies on men's smoking behavior by using data from the 2010 and 2012 waves of the China Family Panel Studies. The results show that stricter drinking policies reduced smoking initiation and the number of cigarettes smoked per day among men by reducing the frequency and quantity of alcohol consumption. Heterogeneity analyses show that the impact of the policy is more pronounced not only for men aged 41-55, but also for men who have higher educational qualifications, who are employed, or who are not members of the Communist Party.

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

FTIR spectroscopy for assessment of hair from lung cancer patients and its application in monitoring the chemotherapy treatment effect.

Lung cancer is the most common cancer and the leading cause of death in China. The current gold standard for clinical lung cancer diagnosis is based on histopathological examination of tumors, but it has the limitation for easy operation and convenient applications. Therefore, researchers are still striving to develop other tools and methods for non-invasive and rapid assessment of the health conditions of lung cancer patients. Hair, as a reflection of the metabolism of the body, is closely related to human health conditions. In principle, Fourier-transform infrared (FTIR) spectroscopy can probe the major chemical compositions in the hair. However, as indicated by previous studies, there is still the challenge to make good use of FTIR spectroscopy for achieving reliable analysis of hair from cancer patients. In this study, hair samples from 82 lung cancer patients were collected and subjected to FTIR measurements and analysis, which showed the protein content in the hair is closely related to the protein content in the blood serum of patients, and the contents of protein and lipid are statistically lower in the lung cancer patients. Furthermore, we demonstrated that FTIR spectroscopy could be employed to monitor the hair of lung cancer patients undergoing chemotherapy, and confirmed that the FTIR spectra of the hair may reflect the resultant effect of the chemotherapy. As such, this work validates the way of using FTIR spectroscopy in hair analysis for the assistance of medical diagnosis of lung cancer as well as monitoring the conditions of the patients under the medical treatment.

Human platelet lysate enhances in vivo activity of CAR-Vδ2 T cells by reducing cellular senescence and apoptosis.

BACKGROUND AIMS: Vγ9Vδ2 T cells are an attractive cell platform for the off-the-shelf cancer immunotherapy as the result of their lack of alloreactivity and inherent multi-pronged cytotoxicity, which could be further amplified with chimeric antigen receptors (CARs). In this study, we sought to enhance the in vivo longevity of CAR-Vδ2 T cells by modulating ex vivo manufacturing conditions and selecting an optimal CAR costimulatory domain. METHODS: Specifically, we compared the anti-tumor activity of Vδ2 T cells expressing anti-CD19 CARs with costimulatory endodomains derived from CD28, 4-1BB or CD27 and generated in either standard fetal bovine serum (FBS)- or human platelet lysate (HPL)-supplemented medium. RESULTS: We found that HPL supported greater expansion of CAR-Vδ2 T cells with comparable in vitro cytotoxicity and cytokine secretion to FBS-expanded CAR-Vδ2 T cells. HPL-expanded CAR-Vδ2 T cells showed enhanced in vivo anti-tumor activity with longer T-cell persistence compared with FBS counterparts, with 4-1BB costimulated CAR showing the greatest activity. Mechanistically, HPL-expanded CAR Vδ2 T cells exhibited reduced apoptosis and senescence transcriptional pathways compared to FBS-expanded CAR-Vδ2 T cells and increased telomerase activity. CONCLUSIONS: This study supports enhancement of therapeutic potency of CAR-Vδ2 T cells through a manufacturing improvement.

Assessment of the Efficacy of the Combination of RNAi of lncRNA DANCR with Chemotherapy to Treat Triple Negative Breast Cancer Using Magnetic Resonance Molecular Imaging.

Long noncoding RNA (lncRNA) differentiation antagonizing noncoding RNA (DANCR) is overexpressed in human triple-negative breast cancer (TNBC) and promotes cell migration and proliferation. TNBC is limited in treatment options relative to hormone-receptor-positive breast cancer and is commonly treated with chemotherapy, which is often compromised by acquired resistance. DANCR has been implicated in the development of chemoresistance across multiple cancer types. Here, we applied magnetic resonance molecular imaging (MRMI) with a targeted contrast agent, MT218, specific to extradomain-B fibronectin (EDB-FN), a marker for epithelial-to-mesenchymal transition, to assess the therapeutic efficacy of the combination of paclitaxel and ZD2-PEG-ECO/siDANCR nanoparticles (ZD2-siDANCR-ELNP) to treat TNBC. The treatment of orthotopic MDA-MB-231 TNBC in mice with paclitaxel significantly suppressed tumor growth but with a significant increase of EDB-FN in the tumor, as revealed by MRMI and immunohistochemistry. Combining ZD2-siDANCR-ELNP with paclitaxel further reduced tumor sizes, along with reduced EDB-FN expression. Interestingly, MT218-MRMI revealed a lower reduction of tumor signal enhancement with the combination treatment than that with the siDANCR treatment alone, which was supported by higher cell density in the tumors treated with the combination therapy, as shown by histochemical analysis. MT218-MRMI clearly revealed the changes of the tumor microenvironment in response to various therapies and is effective to noninvasively assess the response of TNBC tumors to the therapies. Regulating oncogenic lncRNA DANCR is an effective strategy for improving the outcomes of chemotherapy in TNBC.

Association between serum homocysteine and postoperative acute kidney injury in patients undergoing cardiac surgery.

Background: To explore the relationship between homocysteine (Hcy) and cardiac surgery-associated acute kidney injury (AKI). Methods: A total of 944 patients who underwent cardiac surgery were enrolled. The association between Hcy levels and the risk of cardiac surgery-associated AKI was evaluated. Results: A total of 135 patients were diagnosed with AKI and the prevalence of AKI was 14.30%. The AKI group had significantly higher levels of Hcy compared with the non-AKI group (16.90 vs 13.56 umol/l; p < 0.001). The incidence rates of AKI increased from 7.2% to 26.72% across increasing Hcy quartiles (p < 0.001). Compared with the first Hcy quartile group, the odds ratio of cardiac surgery-associated AKI was 4.43 (95% CI: 2.27-8.66) in the highest Hcy group. Conclusion: Elevated Hcy level is an independent risk factor for cardiac surgery-associated AKI.