Exploring the Biogenic Transformation Mechanism of Polyphenols by Lactobacillus plantarum NCU137 Fermentation and Its Enhancement of Antioxidant Properties in Wolfberry Juice.

This study investigated the transformation of polyphenols, including free and bound polyphenols during the fermentation of wolfberry juice by Lactobacillus plantarum NCU137. Results indicated that fermentation significantly increased the free polyphenols content and released bound polyphenols, enhancing the antioxidant activity. Analysis showed that there were 19 free polyphenols, mainly scopoletin, pyrogallol, and dihydroferulic acid, and 16 bound polyphenols, especially p-coumaric acid, feruloyl hexoside, and caffeic acid. A significant correlation was observed between the generation and degradation of polyphenols, and specific bound polyphenols peaked during the 24-48 h fermentation. Furthermore, reduced surface roughness and galacturonic acid content in wolfberry residue, along with increased pectinase activity, suggested substantial pectin degradation in the cell wall, which may be associated with the release of polyphenols, due to pectin serving as carriers for bound polyphenols. The fermentation also increased polyphenol oxidase and peroxidase activity, contributing to polyphenol breakdown. These findings provide insights for improving wolfberry juice production.

Cuproptosis: Advances in Stimulus-Responsive Nanomaterials for Cancer Therapy.

Cuproptosis, a recently identified non-apoptotic programmed cell death modality, attracts considerable attention in the realm of cancer therapeutics owing to its unique cellular demise mechanisms. Since its initial report in 2022, strategies inducing or amplifying cuproptosis for cancer treatment emerge. The engineering of nano-systems to elicit cuproptosis effectively circumvents constraints associated with conventional small-molecule pharmaceutical interventions, presenting novel prospects for oncological therapy. Stimulus-responsive nanomaterials, leveraging their distinctive spatiotemporal control attributes, are investigated for their role in modulating the induction or augmentation of cuproptosis. In this comprehensive review, the physiological characteristics of cuproptosis, encompassing facets such as copper overload and depletion, coupled with regulatory factors intrinsic to cuproptosis, are expounded upon. Subsequently, design methodologies for stimulus-responsive induction or enhancement of cuproptosis, employing stimuli such as light, ultrasound, X-ray, and the tumor microenvironment, are systematically delineated. This review encompasses intricacies in nanomaterial design, insights into the therapeutic processes, and the associated advantages. Finally, challenges inherent in stimulus-responsive induction/enhancement of cuproptosis are deliberated upon and prospective insights into the future trajectory of copper-mediated cancer therapy are provided.

Diagnostic value of dual-time point 68Ga-PSMA PET/CT image for benign and malignant lesions in patients with prostate cancer.

OBJECTIVE: This study aimed to ascertain the diagnostic efficacy of routine 68Ga-PSMA imaging conducted 1 h post-injection, in conjunction with delayed imaging performed 3 h post-injection, for differentiating between benign and malignant lesions in prostate cancer (PCa) patients. METHODS: A retrospective assessment was undertaken on 44 prostate cancer patients who had undergone both routine and delayed 68Ga-PSMA PET/CT scans. Variations in SUVmax and SUVmean values in normal organs, primary prostate cancer sites, metastatic sites, and benign lesions were analyzed. Pathological examination and extended follow-ups were used to confirm all lesions. RESULTS: The study encompassed 44 patients, presenting 35 primary prostate cancer lesions, 44 metastatic lesions, and 30 benign lesions. Delayed imaging (3 h post-injection) demonstrated a decreasing trend in the SUVmax and SUVmean for the liver, blood, and spleen. Conversely, an increasing trend was observed for the parotid, lacrimal, and submandibular glands. For primary lesions, the SUVmax and SUVmean values were 17.63 ± 9.61 and 9.77 ± 5.18 during routine imaging, and 25.09 ± 15.11 and 14.05 ± 8.02 (P < 0.001) during delayed imaging. A comparable increase in SUVmax and SUVmean was seen in the delayed images for metastatic lesions when juxtaposed with routine images. Nevertheless, benign lesions displayed a decrease in SUVmax and SUVmean during delayed imaging when set against routine imaging (SUVmax: 3.56 ± 1.49 vs 2.93 ± 1.47, P = 0.001; SUVmean: 1.99 ± 0.87 vs 1.65 ± 0.87, P = 0.003). CONCLUSION: Imaging using 68Ga-PSMA PET/CT at 3 h post-injection manifested a higher uptake and target-to-background uptake in most malignant prostate cancer lesions, but a diminished uptake in benign lesions. This observation can assist clinicians in distinguishing non-specific PSMA uptake in prostate cancer patients based on PSMA PET/CT image.

Glycyrrhizic acid restores the downregulated hepatic ACE2 signaling in the attenuation of mouse steatohepatitis.

Glycyrrhizic acid (GA), one of the major active components derived from licorice root, exerts liver-protecting activity. Its molecular mechanisms of action, however, remain not completely understood. The angiotensin (Ang) converting enzyme (ACE) 2/Ang-(1-7)/Mas axis, regulated by ACE2 through converting Ang II into Ang-(1-7) to activate Mas receptor, counteracts the pro-inflammatory and pro-steatotic effects of the ACE/Ang II/Ang II receptor type 1 (AT1) axis. Here, it was found that pretreatment with GA suppressed LPS/D-galactosamine-induced serum hyperactivities of alanine aminotransferase and aspartate aminotransferase, hepatomegaly, pathological changes, and over-accumulation of triglycerides and fatty droplets in the liver of mice. GA also diminished LPS/free fatty acid-induced inflammation and steatosis in cultured hepatocytes. Mechanistically, GA restored hepatic protein hypoexpression of ACE2 and Mas receptor, and the decrease in hepatic Ang-(1-7) content. Hepatic overexpression of angiotensin II and AT1 was also suppressed. However, GA did not alter hepatic protein expression of renin and ACE. In addition, GA inhibited hepatic protein over-phosphorylation of the p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and nuclear factor κB at Ser536. Hepatic overexpression of tumor necrosis factor α, interleukin 6, interleukin 1ß, sterol regulatory element-binding protein 1c, and fatty acid synthase was also inhibited. GA-elicited recovery of ACE2 and Mas protein hypoexpression was further confirmed in the hepatocyte. Thus, the present results demonstrate that GA restores the downregulated hepatic ACE2-mediated anti-inflammatory and anti-steatotic signaling in the amelioration of steatohepatitis. We suggest that GA may protect the liver from injury by regulating the hepatic ACE2-mediated signaling.

Topochemical-like bandgap regulation engineering: A bismuth thiooxide nanocatalyst for breast cancer phototherapy.

The physical property tuning of nanomaterials is of great importance in energy, medicine, environment, catalysis, and other fields. Topochemical synthesis of nanomaterials can achieve precise control of material properties. Here, we synthesized a kind of element-doped bismuth-based nanomaterial (BOS) by topochemical-like synthesis and used it for the phototherapy of tumors. In this study, we employed bismuth fluoride nanoflowers as a template and fabricated element-doped bismuth oxide nanoflowers by reduction conditions. The product is consistent with the precursor in crystal structure and nanomorphology, realizing topochemical-like synthesis under mild conditions. BOS can generate reactive oxygen species, consume glutathione, and perform photothermal conversion under 730 nm light irradiation. In vitro and in vivo studies demonstrate that BOS could suppress tumor growth by inducing apoptosis and ferroptosis through phototherapy. Therefore, this study offers a general regulation method for tuning the physical properties of nanomaterials by using a topochemical-like synthesis strategy.

High-Z elements dominated bismuth-based heterojunction nano-semiconductor for radiotherapy-enhanced sonodynamic breast cancer therapy.

Ultrasound and X-rays possess remarkable tissue penetration capabilities, making them promising candidates for cancer therapy. Sonodynamic therapy, which utilizes ultrasound excitation, offers a safer alternative to radiotherapy and can be combined with X-rays to mitigate the adverse effects on normal tissues. In this study, we developed a bismuth-based heterostructure semiconductor (BFIP) to enhance the efficacy of radiotherapy and sonodynamic therapy in treating breast cancer. The semiconductor is fabricated through a two-step process involving the synthesis of porous spherical bismuth fluoride and partially reduced to bismuth oxyiodide. Then, followed by surface modification with amphiphilic polyethylene glycol, BFIP is fabricated. Incorporating heavy atoms in the BFIP enhances radiosensitivity. The BFIP exhibits superior carrier separation efficiency compared to bismuth fluoride, generating a substantial quantity of reactive oxygen species upon ultrasound stimulation. Moreover, the BFIP effectively depletes glutathione through coordination and hole-mediated oxidation pathways, disrupting the tumor microenvironment and inducing oxidative stress. Encouraging results are acquired in both in vitro cell and in vivo tumor models. Our study provides a de-risking strategy by utilizing ultrasound as a partial substitute for X-rays in treating deep-seated tumors, offering a viable research direction for constructing a unified nanoplatform.

Association between preoperative albumin levels and postoperative delirium in geriatric hip fracture patients.

Objective: This study aims to examine the association between preoperative serum albumin levels and postoperative delirium (POD) in geriatric patients who have undergone hip fracture surgery, with the goal of offering novel insights for clinical interventions targeting POD. Methods: A retrospective analysis was conducted on the medical records of patients who underwent hip fracture surgery in a tertiary medical institution from January 2013 to November 2023. The patients were classified based on hypoalbuminemia (defined as a serum albumin level < 35 g/L) and clinical threshold. Multivariable logistic regression and propensity score matching analysis (PSM) were employed to calculate the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for POD to eliminate potential confounding factors. Additionally, subgroup analysis was performed to explore the interaction effect. Results: The retrospective cohort study included 1,440 patients, with an incidence of POD found to be 19.1%. In a multivariable logistic regression analysis, patients with hypoalbuminemia had an adjusted OR of 2.99 (95%CI: 2.14-4.18) compared to those with normal albumin levels (≥ 35 g/L). Furthermore, a significant trend was observed across different severity categories, including mild hypoalbuminemia (34.9-30.0 g/L; adjusted OR = 2.71, 95%CI: 1.84-3.99), moderate hypoalbuminemia (29.9-25.0 g/L, adjusted OR = 3.44, 95%CI: 1.88-6.28), and severe hypoalbuminemia (<25.0 g/L; adjusted OR = 3.97, 95%CI: 1.78-8.86), with a trend value of p <0.001. Similar results were observed in the PSM analysis. Additionally, treating preoperative serum albumin level as a continuous variable, the risk of POD increased by 11% (95% CI, 1.08-1.15) with each 1 g/L decrease in preoperative serum albumin level. Conclusion: Low preoperative levels of albumin are strongly associated with POD in geriatric patients with hip fractures, and a significant dose-response relationship exists between them.

Simultaneous and Sensitive Sensing of Intracellular MicroRNA and mRNA for the Detection of the PI3K/AKT Signaling Pathway in Live Cells.

Simultaneous detection of the concentration variations of microRNA-221 (miRNA-221) and PTEN mRNA molecules in the PI3K/AKT signaling pathway is of significance to elucidate cancer cell migration and invasion, which is useful for cancer diagnosis and therapy. In this work, we show the biodegradable MnO2 nanosheet-assisted and target-triggered DNAzyme recycling signal amplification cascaded approach for the specific detection of the PI3K/AKT signaling pathway in live cells via simultaneous and sensitive monitoring of the variation of intracellular miRNA-221 and PTEN mRNA. Our nanoprobes enable highly sensitive and multiplexed sensing of miRNA-221 and PTEN mRNA with low detection limits of 23.6 and 0.59 pM in vitro, respectively, due to the signal amplification cascades. Importantly, the nanoprobes can be readily delivered into cancer cells and the MnO2 nanosheets can be degraded by intracellular glutathione to release the Mn2+ cofactors to trigger multiple DNAzyme recycling cycles to show highly enhanced fluorescence at different wavelengths to realize sensitive and multiplexed imaging of PTEN mRNA and miRNA-221 for detecting the PI3K/AKT signaling pathway. Moreover, the regulation of PTEN mRNA expression by miRNA-221 upon stimulation by various drugs can also be verified by our method, indicating its promising potentials for both disease diagnosis and drug screening.

Dye-augmented bandgap engineering of a degradable cascade nanoreactor for tumor immune microenvironment-enhanced dynamic phototherapy of breast cancer.

Non-invasive precision tumor dynamic phototherapy has broad application prospects. Traditional semiconductor materials have low photocatalytic activity and low reactive oxygen species (ROS) production rate due to their wide band gap, resulting in unsatisfactory phototherapy efficacy for tumor treatment. Employing the dye-sensitization mechanism can significantly enhance the catalytic activity of the materials. We develop a multifunctional nanoplatform (BZP) by leveraging the benefits of bismuth-based semiconductor nanomaterials. BZP possesses robust ROS generation and remarkable near-infrared photothermal conversion capabilities for improving tumor immune microenvironment and achieving superior phototherapy sensitization. BZP produces highly cytotoxic ROS species via the photocatalytic process and cascade reaction, amplifying the photocatalytic therapy effect. Moreover, the simultaneous photothermal effect during the photocatalytic process facilitates the improvement of therapeutic efficacy. Additionally, BZP-mediated phototherapy can trigger the programmed death of tumor cells, stimulate dendritic cell maturation and T cell activation, modulate the tumor immune microenvironment, and augment the therapeutic effect. Hence, this study demonstrates a promising research paradigm for tumor immune microenvironment-improved phototherapy. STATEMENT OF SIGNIFICANCE: Through the utilization of dye sensitization and rare earth doping techniques, we have successfully developed a biodegradable bismuth-based semiconductor nanocatalyst (BZP). Upon optical excitation, the near-infrared dye incorporated within BZP promptly generates free electrons, which, under the influence of the Fermi energy level, undergo transfer to BiF3 within BZP, thereby facilitating the effective separation of electron-hole pairs and augmenting the catalytic capability for reactive oxygen species (ROS) generation. Furthermore, a cascade reaction mechanism generates highly cytotoxic ROS, which synergistically depletes intracellular glutathione, thereby intensifying oxidative stress. Ultimately, this dual activation strategy, combining oxidative and thermal damage, holds significant potential for tumor immunotherapy.

Increased incidence risks of cardiovascular disease among cancer patients: Evidence from a population-based cohort study in China.

BACKGROUND: Cardiovascular disease (CVD) is becoming a major concern among cancer patients, leading to the development of a new field named cardio-oncology. However, previous studies were mainly based on the western population and focused on CVD mortality. Evidence from the Chinese population is limited. Furthermore, few studies investigated the incidence risks of CVD among cancer patients. METHODS: 85,787 eligible cancer patients were included from Hangzhou city, China. Age-standardized standard incidence ratio (SIR) was used to reflect the incidence risks of CVD among cancer patients as compared with the standard population, which was defined as all residents in Hangzhou city during the same period. RESULTS: After three years of follow-up, cancer patients showed elevated incidence risks of CVD (SIR = 1.41, 95%CI: 1.35-1.47) as compared with the standard population. The elevated risks of CVD were highest in the first year after cancer diagnosis (SIR = 1.68, 95%CI: 1.58-1.78), then followed by the second (SIR = 1.21, 95%CI: 1.11-1.31) and the third (SIR = 1.18, 95%CI: 1.07-1.29) year. These results were consistent in males and females. Furthermore, different risks of CVD were observed among different cancer sites. Patients with pancreatic cancer showed the highest risks of CVD, then followed by liver cancer, lung cancer, kidney cancer, gastric cancer, bladder cancer, prostate cancer, and colorectal cancer. CONCLUSIONS: Cancer patients have increased incidence risks of CVD, especially in the first year after cancer diagnosis. The increased risks of CVD vary by different cancer sites. Our findings highlight the importance of paying close attention to the CVD risks among cancer patients.

Topology-regulated nanocatalysts for ferroptosis-mediated cancer phototherapy.

Ferroptosis-mediated tumor treatment is constrained by the absence of single-component, activatable multifunctional inducers. Given this, a topological synthesis strategy is employed to develop an efficient bismuth-based semiconductor nano-photocatalyst (Bi2O3:S) for tumor ferroptosis therapy. Photo-excited electrons can participate in the reduction reaction to produce harmful reactive oxygen species (ROS) when exposed to near-infrared light. Meanwhile, photo-excited holes can contribute to the oxidation reaction to utilize extra glutathione (GSH) in tumors. In the acidic tumor microenvironment, bismuth ions generated from Bi2O3:S may further cooperate with GSH to amplify oxidative stress damage and achieve biodegradation. Both promote ferroptosis by downregulating glutathione peroxidase 4 (GPX4) expression. Besides, sulfur doping optimizes its near-infrared light-induced photothermal conversion efficiency, benefiting its therapeutic effect. Thus, bismuth ions and holes synergistically drive photo-activable ferroptosis in this nanoplatform, opening up new avenues for tumor therapy.

18F-FDG PET/CT image of pericardial inflammatory myofibroblastic tumor.

Pericardial inflammatory myofibroblastic tumor (IMT) is very rare. Herein, we report fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) findings of pericardial IMT in a 57-year-old woman. On conventional image, it presented as a pericardial mass with heterogeneous delay enhancement. On 18F-FDG PET/CT image, this lesion had mild 18F-FDG uptake with a maximum standardized uptake value (SUVmax) of 1.84. The postoperative pathology supported a diagnosis of IMT. Our case hints us that IMT should be regarded as a differential diagnosis when we meet a solitary pericardial mass with 18F-FDG uptake.

The image quality, amyloid-ß detectability, and acquisition time of clinical florbetapir positron emission tomography in Alzheimer's disease and healthy adults.

Background: Florbetapir positron emission tomography (AV45 PET) is a widely employed modality for detecting cerebral amyloid-ß (Aß) deposition. However, in clinical settings, patients with cognitive impairment are frequently unable to sustain adequate stillness during the scanning procedure. Therefore, we aimed to investigate the effects of a short acquisition time on the image quality and Aß detectability of AV45 PET. Methods: In this cross-sectional study, 29 patients with Alzheimer's disease (AD) and 13 healthy participants underwent 15-minute AV45 PET/magnetic resonance imaging scanning. The PET data were subsequently reconstructed into 15-, 10-, 8-, 6-, 4-, 2-, and 1-minute duration groups (G15, G10, G8, G6, G4, G2, and G1). Subjective PET image quality was scored based on a 5-point Likert scale (poor-excellent: 1-5), and objective image quality was evaluated by the signal-to-noise ratio (SNR) of the 1 cm3 region of interest (ROI) inside the cerebellum. Aß detectability was assessed by the calculation of regional standardized uptake value ratio (SUVR) values in all groups. The Kruskal-Wallis rank sum test and paired t-test were performed to compare the subjective scores, SNR, and SUVR values. The visual inspection was also performed by 2 nuclear physicians to give a binary diagnosis to each case. Results: The subjective scores were decreased in the groups with shortened scanning time relative to the G15 group (4.67±0.48, all P<0.05). Notably, a good image quality score was also given to the G10 group (4.40±0.63), and sufficient image quality could be achieved with the G8 (3.86±0.68) and G6 (3.14±0.52) groups. The SNR values were decreased by 10.33%, 17.74%, and 23.26% in the G10, G8, and G6 group, respectively (all P<0.05). Compared with the G15 group (1.48±0.16), the composite SUVR values were increased in the G10 (1.50±0.16), G8 (1.50±0.17), and G6 groups (1.51±0.18, all P<0.05). By visual inspection, the diagnoses of each case in the G10, G8, and G6 group were identical with those in the G15 group. Conclusions: The acquisition time of AV45 PET is required to reach at least 6 minutes to achieve acceptable image quality and maintained Aß detectability.

Polymer composite microspheres loading 177Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer.

BACKGROUND: Transarterial radioembolization (TARE) with 90Y-labeled glass and resin microspheres is one of the primary treatment strategies for advanced-stage primary and metastatic hepatocellular carcinoma (HCC). However, difficulties of real-time monitoring post administration and embolic hypoxia influence treatment prognosis. In this study, we developed a new biodegradable polymer microsphere that can simultaneously load 177Lu and MgO nanoparticle, and evaluated the TARE therapeutic efficacy and biosafety of 177Lu-PDA-CS-MgO microspheres for HCC treatment. METHODS: Chitosan microspheres were synthesized through emulsification crosslink reaction and then conducted surface modification with polydopamine (PDA). The 177Lu and nano MgO were conjugated to microspheres using active chemical groups of PDA. The characteristics of radionuclide loading efficiency, biodegradability, blood compatibility, and anti-tumor effectwere evaluated both in vitro and in vivo. SPECT/CT imaging was performed to monitor bio-distribution and bio-stability of 177Lu-PDA-CS-MgO after TARE treatment. The survival duration of each rat was monitored. HE analysis, TUNEL analysis, immunohistochemical analysis, and western blot analysis were conducted to explore the anti-tumor effect and mechanism of composited microspheres. Body weight, liver function, blood routine examination were monitored at different time points to evaluate the bio-safety of microspheres. RESULTS: The composite 177Lu-PDA-CS-MgO microsphere indicated satisfactory degradability, biocompatibility, radionuclide loading efficiency and radiochemical stability in vitro. Cellular evaluation showed that 177Lu-PDA-CS-MgO had significant anti-tumor effect and blocked tumor cell cycles in S phase. Surgical TARE treatment with 177Lu-PDA-CS-MgO significantly prolonged the medial survival time from 49 d to 105 d, and effectively inhibited primary tumor growth and small metastases spreading. Moreover, these microspheres indicated ideal in vivo stability and allowed real-time SPECT/CT monitoring for up to 8 weeks. Immunostaining and immunoblotting results also confirmed that 177Lu-PDA-CS-MgO had potential in suppressing tumor invasion and angiogenesis, and improved embolic hypoxia in HCC tissues. Further evaluations of body weight, blood test, and pathological analysis indicated good biosafety of 177Lu-PDA-CS-MgO microspheres in vivo. CONCLUSION: Our study demonstrated that 177Lu-PDA-CS-MgO microsphere hold great potential as interventional brachytherapy candidate for HCC therapy. Polymer composite microspheres loading 177Lu radionuclide and MgO nanoparticles for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer.

IFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus.

Norovirus is a leading cause of epidemic viral gastroenteritis, with no currently approved vaccines or antivirals. Murine norovirus (MNoV) is a well-characterized model of norovirus pathogenesis in vivo, and persistent strains exhibit lifelong intestinal infection. Interferon-λ (IFN-λ) is a potent antiviral that rapidly cures MNoV. We previously demonstrated that IFN-λ signaling in intestinal epithelial cells (IECs) controls persistent MNoV, and here demonstrate that IFN-λ acts on tuft cells, the exclusive site of MNoV persistence, to limit infection. While interrogating the source of IFN-λ to regulate MNoV, we confirmed that MDA5-MAVS signaling, required for IFN-λ induction to MNoV in vitro, controls persistent MNoV in vivo. We demonstrate that MAVS in IECs and not immune cells controls MNoV. MAVS in nonsusceptible enterocytes, but not in tuft cells, restricts MNoV, implicating noninfected cells as the IFN-λ source. Our findings indicate that host sensing of MNoV is distinct from cellular tropism, suggesting intercellular communication between IECs for antiviral signaling induction in uninfected bystander cells.

Topological Regulating Bismuth Nano-Semiconductor for Immunogenic Cell Death-Mediated Sonocatalytic Hyperthermia Therapy.

Immunogenic cell death (ICD) can activate the body's immune system via dead cell antigens to achieve immunotherapy. Currently, small molecule drugs have been used for ICD treatment in clinical, however, how to precisely control the induced ICD while treating tumors is of great significance for improving therapeutic efficacy. Based on this, a sono/light dual response strategy to tumor therapy and activation of ICD is proposed. A topological synthesis method is used to obtain sulfur-doped bismuth oxide Bi2 O3-x Sx (BS) using BiF3 (BF) as a template through reduction and a morphology-controllable bismuth-based nano-semiconductor with a narrow bandgap is constructed. Under the stimulation of ultrasound, BS can produce reactive oxygen species (ROS) through the sonocatalytic process, which cooperates with BS to consume glutathione and enhance cellular oxidative damage, further inducing ICD. Due to the introduction of sulfur in the reduction reaction, BS can achieve photothermal conversion under light, and combine with ROS to treat tumors. Further, with the assistance of ivermectin (IVM) to form composite (BSM), combined with sono/light dual strategy, ICD is promoted and DCs maturation is accelerated. The proposed ICD-mediated hyperthermia/sonocatalytic therapy strategy will pay the way for synergetic enhancement of tumor treatment efficacy and provide a feasible idea for controllable induction of ICD.

Mass Tuberculosis Screening Among the Elderly: A Population-Based Study in a Well-Confined, Rural County in Eastern China.

BACKGROUND: Mass tuberculosis (TB) screening has been recommended in certain high-risk populations. However, population-based screening interventions have rarely been implemented. Whether mass screening improves health equity is unknown. METHODS: We implemented a mass TB screening intervention among elderly persons (>60 years old) in Lanxi County, China. Standardized questionnaires, physical examinations, and chest radiographs (CXRs) were administered to all participants. Systematic testing with computed tomography, smear, culture, or Xpert was performed among persons with an abnormal CXR. We assessed TB prevalence per 100 000 persons and constructed multivariable regression models among subgroups that were and were not screened. Medical insurance was categorized as participation in either a basic program with limited coverage or a more comprehensive coverage program. RESULTS: In total, 49 339 individuals (32% of the elderly population in Lanxi) participated in the screening. One hundred fifteen screened persons were diagnosed with TB (233 cases per 100 000 persons), significantly higher than persons not screened (168 cases among 103 979 person-years; prevalence-to-case notification ratio, 1.44 [95% confidence interval {CI}, 1.14-1.83]). This increase was largely driven by diagnosis of asymptomatic disease during mass screening (n = 57 [50% of participants with TB]). Participants with basic medical insurance were much more likely to be diagnosed through mass screening than by passive detection (adjusted odds ratio, 4.52 [95% CI, 1.35-21.28]). CONCLUSIONS: In a population-based, mass TB screening intervention encompassing >30% of the elderly population in a county in rural China, case finding was 44% higher than background detection, driven by diagnosis of TB without recognized symptoms. Importantly, mass screening identified TB in people with limited healthcare options who were less likely to be found through background case detection.

Restricting epigenetic activity promotes the reprogramming of transformed cells to pluripotency in a line-specific manner.

Somatic cell reprogramming and oncogenic transformation share surprisingly similar features, yet transformed cells are resistant to reprogramming. Epigenetic barriers must block transformed cells from reprogramming, but the nature of those barriers is unclear. In this study, we generated a systematic panel of transformed mouse embryonic fibroblasts (MEFs) using oncogenic transgenes and discovered transformed cell lines compatible with reprogramming when transfected with Oct4/Sox2/Klf4/Myc. By comparing the reprogramming-capable and incapable transformed lines we identified multiple stages of failure in the reprogramming process. Some transformed lines failed at an early stage, whilst other lines seemed to progress through a conventional reprogramming process. Finally, we show that MEK inhibition overcomes one critical reprogramming barrier by indirectly suppressing a hyperacetylated active epigenetic state. This study reveals that diverse epigenetic barriers underly resistance to reprogramming of transformed cells.

Light-Elicited and Oxygen-Saved Iridium Nanocapsule for Oxidative Damage Intensified Oncotherapy.

Regulating redox homeostasis in tumor cells and exploiting oxidative stress to damage tumors is an efficacious strategy for cancer therapy. However, the strengths of organic nanomaterials within this strategy are often ignored. In this work, a light-triggered reactive oxygen species (ROS) damaging nanoamplifier (IrP-T) was developed for enhanced photodynamic therapy (PDT). The IrP-T was fabricated with an amphiphilic iridium complex and a MTH1 inhibitor (TH287). Under green light stimulation, IrP-T catalyzed the oxygen in cells to generate ROS for realizing oxidative damage; meanwhile, TH287 increased the accumulation of 8-oxo-dGTP, further strengthening oxidative stress and inducing cell death. IrP-T could maximize the use of a small amount of oxygen, thus further boosting the efficacy of PDT in hypoxic tumors. The construction of nanocapsules provided a valuable therapeutic strategy for oxidative damage and synergizing PDT.