Toxicity assessment of Cucurbita pepo cv Dayangua and its effects on gut microbiota in mice.

BACKGROUND: Cucurbita pepo cv Dayangua (CPD) is an edible plant with diverse pharmacological properties. The current research on CPD has primarily focused on initial investigations of its chemical composition and pharmacological effects, and no comprehensive toxicity assessment has been conducted to date. METHODS: In the present study, the toxicity of CPD was evaluated through both acute and sub-chronic oral toxicity tests in mice. 16S rDNA sequencing was used to analyze the composition of the gut microbiota of mice at different time points to observe the effect of CPD on these microbial communities. RESULTS: In the acute toxicity test, CPD exhibited low toxicity, with a median lethal dose (LD50) > 2000 mg/kg. The sub-chronic toxicity test indicated that CPD administration at doses of 200, 400, and 600 mg/kg did not cause mortality or significant organ damage in mice. Furthermore, analysis of the gut microbiota after gavage administration of CPD at 400 and 600 mg/kg revealed an improved abundance of some beneficial gut bacteria. CONCLUSIONS: In summary, no acute or sub-chronic toxic effects were observed in mice following the oral administration of CPD. CPD did not affect the structure and diversity of the gut microbiota and may contribute to an increase in the number of beneficial gut bacteria.

Nodular Vulvar Lesions.

A woman in her 30s presented with mildly itchy skin nodules in the vulvar region for 1 year, which occurred during pregnancy and increased gradually in size and number without any treatments. What is your diagnosis?

The measurement and correlation analysis of scleral and choroid thickness in branch retinal vein occlusion.

To use Optical Coherence Tomography (OCT) to measure scleral thickness (ST) and subfoveal choroid thickness (SFCT) in patients with Branch Retinal Vein Occlusion (BRVO) and to conduct a correlation analysis. A cross-sectional study was conducted. From May 2022 to December 2022, a total of 34 cases (68 eyes) of untreated unilateral Branch Retinal Vein Occlusion (BRVO) patients were recruited at the Affiliated Eye Hospital of Nanchang University. Among these cases, 31 were temporal branch vein occlusions, 2 were nasal branch occlusions, and 1 was a superior branch occlusion. Additionally, 39 cases (39 eyes) of gender- and age-matched control eyes were included in the study. Anterior Segment Optical Coherence Tomography (AS-OCT) was used to measure ST at 6 mm superior, inferior, nasal, and temporal to the limbus, while Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) was used to measure SFCT. The differences in ST and SFCT between the affected eye, contralateral eye, and control eye of BRVO patients were compared and analyzed for correlation. The axial lengths of the BRVO-affected eye, contralateral eye, and control group were (22.92 ± 0.30) mm, (22.89 ± 0.32) mm and (22.90 ± 0.28) mm respectively, with no significant difference in axial length between the affected eye and contralateral eye (P > 0.05). The SFCT and ST measurements in different areas showed significant differences between the BRVO-affected eye, contralateral eye in BRVO patients (P < 0.05). The CRT of BRVO-affected eyes was significantly higher than that of the contralateral eyes and the control eyes (P < 0.001). In comparison between BRVO-affected eyes and control eyes, there were no statistically significant differences in age and axial length between the two groups (P > 0.05). However, significant differences were observed in SFCT and temporal, nasal, superior, and inferior ST between the two groups (P < 0.05). The difference in temporal ST between the contralateral eyes and the control eyes was not statistically significant (t = - 0.35, P = 0.73). However, the contralateral group showed statistically significant increases in SFCT, nasal, superior and inferior ST compared to control eyes (t = - 3.153, 3.27, 4.21, 4.79, P = 0.002, 0.002, < 0.001, < 0.001). However, the difference between the CRT of the contralateral and control eyes was not statistically significant (P = 0.421). When comparing SFCT and ST between BRVO-affected eyes with and without macular edema, no statistically significant differences were found (t = - 1.10, 0.45, - 1.30, - 0.30, 1.00; P = 0.28, 0.66, 0.21, 0.77, 0.33). The thickness of SFCT and temporal ST in major BRVO group is higher than the macular BRVO group and the difference was statistically significant (t = 6.39, 7.17, P < 0.001 for all). Pearson correlation analysis revealed that in BRVO patients, there was a significant positive correlation between SFCT/CRT and temporal ST (r = 0.288, 0.355, P = 0.049, 0.04). However, there was no correlation between SFCT/CRT and nasal ST, superior ST, and inferior ST (P > 0.05). In BRVO patients, both SFCT/CRT and ST increase, and there is a significant correlation between SFCT/CRT and the ST at the site of vascular occlusion.

Early onset and liver failure indicating poor prognosis of infant liver failure syndrome type 1.

BACKGROUND: Infantile liver failure syndrome type 1 (ILFS1, OMIM #615,438), caused by leucyl-tRNA synthase 1 (LARS1, OMIM *151,350) deficiency, is a rare autosomal-recessive disorder. The clinical manifestations, molecular-genetic features, and prognosis of LARS1 disease remain largely elusive. METHODS: Three new instances of ILFS1 with confirmed variants in LARS1, encoding LARS1, were identified. Disease characteristics were summarized together with those of 33 reported cases. Kaplan-Meier analysis was performed to assess prognostic factors in ILFS1 patients. RESULTS: The 3 new ILFS1 patients harbored 6 novel variants in LARS1. Among the 36 known patients, 12 died or underwent liver transplantation. The main clinical features of ILFS1 were intrauterine growth restriction (31/32 patients in whom this finding was specifically described), failure to thrive (30/31), hypoalbuminemia (32/32), microcytic anemia (32/33), acute liver failure (24/34), neurodevelopmental delay (25/30), seizures (22/29), and muscular hypotonia (13/27). No significant correlations were observed between genotype and either presence of liver failure or clinical severity of disease. Kaplan-Meier analysis indicated that age of onset < 3mo (p = 0.0015, hazard ratio = 12.29, 95% confidence interval [CI] = 3.74-40.3), like liver failure (p = 0.0343, hazard ratio = 6.57, 95% CI = 1.96-22.0), conferred poor prognosis. CONCLUSIONS: Early age of presentation, like liver failure, confers poor prognosis in ILFS1. Genotype-phenotype correlations remain to be established.

Lanatoside C induces ferroptosis in non-small cell lung cancer in vivo and in vitro by regulating SLC7A11/GPX4 signaling pathway.

Background: Non-small cell lung cancer (NSCLC) is a common malignant tumor worldwide, remaining resistant to chemotherapy drugs. Lanatoside C can inhibit the growth of cancer cell lines. In this study we aimed to investigate the relationship between lanatoside C and ferroptosis, exploring the possible mechanism in NSCLC. Methods: Experiments in vitro and in vivo were conducted. A549 cells were used for in vitro, including cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) release, western blotting, flow cytometry, transmission electron microscopy (TEM), and confocal microscopy. In vivo, a subcutaneous tumor model in nude mice using A549 cells was built and body size of the mice was observed. Ki67 immunohistochemistry, hematoxylin-eosin (HE) staining, and western blotting were conducted respectively. Results: The results showed that lanatoside C had an inhibitory effect on the growth of A549 cells, and the dose of lanatoside C used in this experiment was set at 0.4 µM for 24 hours. When A549 cells were treated with lanatoside C, the cell viability was decreased observably (P<0.001) and LDH release was significantly enhanced (P<0.01) compared with the control group. However, when A549 cells were treated together with lanatoside C and five different inhibitors, containing ferroptosis inhibitors, necroptosis inhibitors, apoptosis inhibitors, pyroptosis inhibitors, and autophagy inhibitors, the results showed that the viability of A549 cells with lanatoside C and ferrostatin-1 (Fer-1) was reduced (P>0.05) and the LDH release was significantly enhanced (P<0.05). Besides, TEM and confocal microscopy showed that the mitochondria of A549 cells in the lanatoside C group disappeared and the mitochondrial membrane potential decreased. In vivo, lanatoside C efficiently enhanced the sensitivity of the xenograft tumors, as well as reducing the size and weight of the tumor. Moreover, immunohistochemical staining analysis revealed that the SLC7A11 and GPX4 levels significantly decreased in the lanatoside C group. In addition, the expression of GPX4 and SLC7A11 by western blotting was decreased in lanatoside C group. Conclusions: Collectively, lanatoside C could inhibit the proliferation and induce ferroptosis, and have a biological effect on inducing ferroptosis in NSCLC.

SleepFC: Feature Pyramid and Cross-Scale Context Learning for Sleep Staging.

Automated sleep staging is essential to assess sleep quality and treat sleep disorders, so the issue of electroencephalography (EEG)-based sleep staging has gained extensive research interests. However, the following difficulties exist in this issue: 1) how to effectively learn the intrinsic features of salient waves from single-channel EEG signals; 2) how to learn and capture the useful information of sleep stage transition rules; 3) how to address the class imbalance problem of sleep stages. To handle these problems in sleep staging, we propose a novel method named SleepFC. This method comprises convolutional feature pyramid network (CFPN), cross-scale temporal context learning (CSTCL), and class adaptive fine-tuning loss function (CAFTLF) based classification network. CFPN learns the multi-scale features from salient waves of EEG signals. CSTCL extracts the informative multi-scale transition rules between sleep stages. CAFTLF-based classification network handles the class imbalance problem. Extensive experiments on three public benchmark datasets demonstrate the superiority of SleepFC over the state-of-the-art approaches. Particularly, SleepFC has a significant performance advantage in recognizing the N1 sleep stage, which is challenging to distinguish.

Eigen microstates in self-organized criticality.

We employ the eigen microstates approach to explore the self-organized criticality (SOC) in two celebrated sandpile models, namely the BTW model and the Manna model. In both models, phase transitions from the absorbing state to the critical state can be understood by the emergence of dominant eigen microstates with significantly increased weights. Spatial eigen microstates of avalanches can be uniformly characterized by a linear system size rescaling. The first temporal eigen microstates reveal scaling relations in both models. Furthermore, by finite-size scaling analysis of the first eigen microstates, we numerically estimate critical exponents, i.e., sqrt[σ_{0}w_{1}]/v[over ̃]_{1}∝L^{D} and v[over ̃]_{1}∝L^{D(1-τ_{s})/2}. Our findings could provide profound insights into eigen microstates of the universality and phase transition in nonequilibrium complex systems governed by self-organized criticality.

Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis.

OBJECTIVES: Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms. METHODS: In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins. RESULTS: PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system. CONCLUSION: PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.

Safety and efficacy of parsaclisib in combination with rituximab, bendamustine + rituximab, or ibrutinib in patients with previously treated B-cell lymphoma: analysis of a phase 1 dose-finding study (CITADEL­112).

Parsaclisib, a potent and highly selective phosphoinositide 3-kinase δ inhibitor, has shown clinical activity in relapsed/refractory (R/R) B-cell lymphoma. The phase 1 CITADEL-112 (NCT03424122) study assessed safety and efficacy of parsaclisib in combination with investigator choice standard of care (SOC; rituximab [Treatment A], rituximab plus bendamustine [Treatment B], or ibrutinib [Treatment C]) in 50 patients with R/R B-cell lymphoma. The most common treatment-emergent adverse events included neutropenia (62.5%, 50.0%, and 50.0% of patients in Treatments A, B, and C, respectively); diarrhea (37.5%) and anemia (31.3%) in Treatment A; abdominal pain, asthenia, diarrhea, and nausea (each 33.3%) in Treatment B; and increased alanine and aspartate aminotransferase (each 37.5%) in Treatment C. Objective responses were observed in 13 patients (81.3%) in Treatment A, 10 (55.6%) in Treatment B, and 8 (50.0%) in Treatment C. Parsaclisib combined with SOC therapies had an expected safety profile and promising efficacy in patients with R/R B-cell lymphomas.

Enantioselective Formal 1,2-Diamination of Ketenes with Iminosulfinamides: Asymmetric Synthesis of Unnatural α,α-Disubstituted α-Amino Acid Derivatives.

A method was developed for the enantioselective formal 1,2-diamination of disubstituted ketenes using iminosulfinamides as nitrogen sources. The protocol involves the addition of lithium iminosulfinamides to ketenes to form N-iminosulfinyl amide metalloenolates. These metalloenolates then undergo a [2,3]-sigmatropic rearrangement to yield unnatural α,α-disubstituted α-amino acid derivatives with high enantiopurity. The chirality present at the sulfur atom in the iminosulfinamides is effectively transferred to α carbon of the resulting products, facilitating the highly enantioselective amination of ketenes.

Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.

BACKGROUND: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC) patients; therefore, establishing a new predictive stage is necessary. AIM: To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. METHODS: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan-Meier survival curves and Cox regression model. RESULTS: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor-node-metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P < 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant (P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P < 0.05). CONCLUSION: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.

Chemodivergence in Fluorine Source-Controlled Cascade Reaction of Aryne Precursors to Synthesize Pyrrolo[3,4-b]indoles and 3-Arylated Maleimides.

Reactions allowing chemodivergence prove to be attractive strategies in synthetic organic chemistry. We herein described a highly practical, transition-metal-free, highly regioselective and chemodivergent cascade reaction controlled by fluorine sources, which involved a [3 + 2] cycloaddition or C-arylation process between aryne precursors and 3-aminomaleimides. These two pathways led to a wide scope of structurally diverse pyrrolo[3,4-b]indoles (19 examples) and 3-arylated maleimides (25 examples) in good-to-excellent yields. Furthermore, the reaction could be scaled up, and several synthetic transformations were accomplished for the preparation of functionalized molecules and might provide new opportunities for the discovery of N-heterocyclic drugs.

A novel chitosan/cellulose phosphonate composite hydrogel for ultrafast and efficient removal of Pb(II) and Cu(II) from wastewater.

Developing green and high-performance adsorbents to separate heavy metals from wastewater is a challenging task. Biomass hydrogel has the advantages of low cost, renewability, and biodegradability, but it has the problem of low adsorption efficiency. Herein, a novel chitosan/cellulose phosphonate composite hydrogel(CS/MCCP) is fabricated by two steps of reactions including the Phosphorylation reaction and the Mannich reaction. As an excellent chelating group, the phosphonate group greatly enhances the adsorption efficiency of the biomass hydrogel. The CS/MCCP shows ultrafast adsorption rate and excellent adsorption capacity for Pb(II) and Cu(II). The saturated adsorption capacity of Pb(II) and Cu(II) is 211.42 and 74.29 mg·g-1, respectively. The adsorption equilibration time is only 10 min. The adsorption performance of the CS/MCCP is superior to that of the reported cellulose/chitosan hydrogels. Besides, an in-depth analysis of the adsorption mechanism is conducted using X-ray photoelectron spectroscopy(XPS) combined with Density Functional Theory(DFT) calculation. The results reveal that the adsorption mechanism is electrostatic attraction and surface complexation, and there is a synergistic coordination between the phosphonate groups and the amino groups.

Protopanaxadiol improves lupus nephritis by regulating the PTX3/MAPK/ERK1/2 pathway.

Lupus nephritis (LN) is a kidney disease that occurs after systemic lupus erythematosus (SLE) affects the kidneys. Pentraxin 3 (PTX3) is highly expressed in the serum of patients with LN. Renal PTX3 deposition is directly related to clinical symptoms such as proteinuria and inflammation. The excessive proliferation of mesangial cells (MCs) is one of the representative pathological changes in the progression of LN, which is closely related to its pathogenesis. Protopanaxadiol (PPD) is the main component of ginsenoside metabolism and has not been reported in LN. The aim of this study was to investigate the relationship between PTX3 and mesangial cell proliferation and to evaluate the potential role and mechanism of PPD in improving LN. PTX3 is highly expressed in the kidneys of LN patients and LN mice and is positively correlated with renal pathological indicators, including proteinuria and PCNA. The excessive expression of PTX3 facilitated the proliferation of MCs, facilitated the activation of the MAPK/ERK1/2 signaling pathway, and increased the expression of HIF-1α. Further studies showed that PPD can effectively inhibit the abnormal proliferation of MCs with high expression of PTX3 and significantly improve LN symptoms such as proteinuria in MRL/lpr mice. The mechanism may be related to the inhibition of the PTX3/MAPK/ERK1/2 pathway. In this study, both in vitro, in vivo, and clinical sample results show that PTX3 is involved in the regulation of MCs proliferation and the early occurrence of LN. Natural active compound PPD can improve LN by regulating the PTX3/MAPK/ERK1/2 pathway.

Radionuclide-Labeled Antisilencing Function 1a Inhibitory Peptides for Tumor Identification and Individualized Therapy.

Immune checkpoint blockade (ICB) therapy is promising to revolutionize cancer regimens, but the low response rate and the lack of a suitable patient stratification method have impeded universal profit to cancer patients. Noninvasive positron emission tomography (PET) imaging in the whole body, upon coupling with specific biomarkers closely related to the immune response, could provide spatiotemporal information to prescribe cancer therapy. Herein, we demonstrate that antisilencing function 1a (ASF1a) could serve as a biomarker target to delineate tumor immune microenvironments by immune PET (iPET). The iPET radiotracer (68Ga-AP1) is designed to target ASF1a in tumors and predict immune response, and the signal intensity predicts anti-PD-1 (αPD-1) therapy response in a negative correlation manner. The ICB-resistant tumors with a high level of ASF1a as revealed by iPET (ASF1aHigh-iPET) are prescribed to be treated by either the combined 177Lu-labeled AP1 and αPD-1 or the standalone α particle-emitting 225Ac-labeled AP1, both achieving enhanced therapeutic efficacy and prolonged survival time. Our study not only replenishes the iPET arsenal for immune-related response evaluation by designing a reliable biomarker and a facile radiotracer but also provides optional therapeutic strategies for ICB-resistant tumors with versatile radionuclide-labeled AP1 peptides, which is promising for real-time clinical diagnosis and individualized therapy planning simultaneously.

Total weight loss rather than preoperative body mass index correlates with remission of irregular menstruation after sleeve gastrectomy in patients with polycystic ovary syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. Some retrospective studies with small sample sizes have reported that bariatric metabolic surgery is effective in remission of irregular menstruation in patients with PCOS and obesity. However, the correlation between preoperative body mass index (BMI), postoperative weight loss, and remission of irregular menstruation in patients with obesity and PCOS after sleeve gastrectomy (SG) is lack of consensus. Methods: We enrolled 229 participants with obesity and PCOS who underwent SG. All patients were followed up for one year after surgery. Remission of irregular menstruation was defined as a spontaneous consecutive six-month menstrual cycle in one year. Subgroup analysis was conducted using tertiles of preoperative BMI and postoperative total weight loss (TWL)% to determine their correlation with the remission of irregular menstruation after SG. Results: 79.03% (181/229) patients achieved remission of irregular menstruation one year after SG with a TWL% of 33.25 ± 0.46%. No significant difference was detected in the remission rate among the subgroups with different BMI (P=0.908). TWL% was correlated with the remission of irregular menstruation (OR 1.78, 95% CI 1.18-2.69, P<0.05). Conclusions: SG had a significant effect on the remission of irregular menstruation in patients with obesity and PCOS. Preoperative BMI did not emerge as a decisive factor correlated with remission; instead, TWL% showed potential as a key factor.

Adsorption of Hg2+/Cr6+ by metal-binding proteins heterologously expressed in Escherichia coli.

BACKGROUND: Removal of heavy metals from water and soil is a pressing challenge in environmental engineering, and biosorption by microorganisms is considered as one of the most cost-effective methods. In this study, the metal-binding proteins MerR and ChrB derived from Cupriavidus metallidurans were separately expressed in Escherichia coli BL21 to construct adsorption strains. To improve the adsorption performance, surface display and codon optimization were carried out. RESULTS: In this study, we constructed 24 adsorption engineering strains for Hg2+ and Cr6+, utilizing different strategies. Among these engineering strains, the M'-002 and B-008 had the strongest heavy metal ion absorption ability. The M'-002 used the flexible linker and INPN to display the merRopt at the surface of the E. coli BL21, whose maximal adsorption capacity reached 658.40 µmol/g cell dry weight under concentrations of 300 µM Hg2+. And the B-008 overexpressed the chrB in the intracellular, its maximal capacity was 46.84 µmol/g cell dry weight under concentrations 500 µM Cr6+. While in the case of mixed ions solution (including Pb2+, Cd2+, Cr6+ and Hg2+), the total amount of ions adsorbed by M'-002 and B-008 showed an increase of up to 1.14- and 4.09-folds, compared to the capacities in the single ion solution. CONCLUSION: The construction and optimization of heavy metal adsorption strains were carried out in this work. A comparison of the adsorption behavior between single bacteria and mixed bacteria systems was investigated in both a single ion and a mixed ion environment. The Hg2+ absorption capacity is reached the highest reported to date with the engineered strain M'-002, which displayed the merRopt at the surface of chassis cell, indicating the strain's potential for its application in practical environments.

Cyclin-dependent kinase inhibitor 1A inhibits pyroptosis to enhance human lung adenocarcinoma cell radioresistance by promoting DNA repair.

Purpose: One of the best anticancer treatments available is radiotherapy, which can be used either alone or in conjunction with other forms of treatment including chemotherapy and surgery. Nevertheless, a number of biochemical and physiological processes that react to ionizing radiation might provide tumor cells radioresistance, which makes radiotherapy ineffective. It has been found that CDKN1A regulates DNA damage repair, which contributes to tumor radioresistance. However, the precise mechanism is still unknown. Therefore, this study aimed to explore the mechanisms underlying CDKN1A-enhanced radioresistance in tumor cells. Methods: Cells were irradiated with 4 Gy after CDKN1A overexpression or knockdown. CDKN1A expression was measured using real-time PCR, cell viability was evaluated using cell counting kit-8 and colony formation assays, and cytotoxicity was assessed using a lactate dehydrogenase assay. Pyroptosis in cells was analyzed using caspase-1 activity assay, enzyme-linked immunosorbent assay, and flow cytometry. Inflammation activation was detected through a co-immunoprecipitation assay. Activation of pyroptosis-related proteins was analyzed using immunohistochemistry, Western blot, and immunofluorescence. Tumor radioresistance in vivo was evaluated in a mouse xenograft model. Results: Radiotherapy upregulated CDKN1A expression, which promoted lung adenocarcinoma cell survival. CDKN1A influenced radiation-induced pyroptosis in A549, which mainly depended on inhibiting the activation of the AIM2 inflammasome by promoting DNA repair. Additionally, CDKN1A upregulation enhanced A549 xenograft tumor radioresistance by inhibiting radiation-induced pyroptosis in vivo. Conclusions: CDKN1A inhibits pyroptosis to enhance the radioresistance of lung adenocarcinoma cells by promoting DNA repair. This study may serve as a reference for developing novel targeted therapies against cancer.

Mitochondria-Modulating Liposomes Reverse Radio-Resistance for Colorectal Cancer.

Complete remission of colorectal cancer (CRC) is still unachievable in the majority of patients by common fractionated radiotherapy, leaving risks of tumor metastasis and recurrence. Herein, clinical CRC samples demonstrated a difference in the phosphorylation of translation initiation factor eIF2α (p-eIF2α) and the activating transcription factor 4 (ATF4), whose increased expression by initial X-ray irradiation led to the resistance to subsequent radiotherapy. The underlying mechanism is studied in radio-resistant CT26 cells, revealing that the incomplete mitochondrial outer membrane permeabilization (iMOMP) triggered by X-ray irradiation is key for the elevated expression of p-eIF2α and ATF4, and therefore radio-resistance. This finding guided to discover that metformin and 2-DG are synergistic in reversing radio resistance by inhibiting p-eIF2α and ATF4. Liposomes loaded with metformin and 2-DG (M/D-Lipo) are thus prepared for enhancing fractionated radiotherapy of CRC, which achieved satisfactory therapeutic efficacy in both local and metastatic CRC tumors by reversing radio-resistance and preventing T lymphocyte exhaustion.