Surgery challenges and postoperative complications of lung cancer after neoadjuvant immunotherapy.

BACKGROUND: In China, real-world data on surgical challenges and postoperative complications after neoadjuvant immunotherapy of lung cancer are limited. METHODS: Patients were retrospectively enrolled from January 2018 to January 2023, and their clinical and pathological characters were subsequently analyzed. Surgical difficulty was categorized into a binary classification according to surgical duration: challenging or routine. Postoperative complications were graded using Clavien-Dindo grades. Logistic regression was used to identify risk factors affecting the duration of surgery and postoperative complications greater than Clavien-Dindo grade 2. RESULTS: In total, 261 patients were included. Of these, stage III patients accounted for 62.5% (163/261) at initial diagnosis, with 25.3% (66/261) at stage IIIB. Central-type non-small-cell lung cancer accounted for 61.7% (161/261). One hundred and forty patients underwent video-assisted thoracoscopic surgery and lobectomy accounted for 53.3% (139/261) of patients. Surgical time over average duration was defined as challenging surgeries, accounting for 43.7%. The postoperative complications rate of 261 patients was only 22.2%. Smoking history (odds ratio [OR] = 9.96, 95% [CI] 1.15-86.01, p = 0.03), chemoimmunotherapy (OR = 2.89, 95% CI 1.22-6.86, p = 0.02), and conversion to open surgery (OR = 11.3, 95% CI 1.38-92.9, p = 0.02) were identified as independent risk factors for challenging surgeries, while pneumonectomy (OR = 0.36, 95% CI 0.15-0.86, p= 0.02) was a protective factor. Meanwhile, pneumonectomy (OR = 7.51, 95% CI 2.40-23.51, p < 0.01) and challenging surgeries (OR = 5.53, 95% CI 1.50-20.62, p = 0.01) were found to be risk factors for postoperative complications greater than Clavien-Dindo grade 2. CONCLUSIONS: Compared to immunotherapy alone or in combination with apatinib, neoadjuvant chemoimmunotherapy could increase the difficulty of surgery while the incidence of postoperative complications remained acceptable. The conversion to open surgery and pneumonectomy after neoadjuvant immunotherapy should be reduced.

Whole Genome Sequence Analysis of Two Oxacillin-Resistant and mecA-Positive Strains of Staphylococcus haemolyticus Isolated from Ear Swab Samples of Patients with Otitis Media.

Objective: Staphylococcus haemolyticus can cause a series of infections including otitis media (OM), and the oxacillin-resistant S. haemolyticus has become a serious health concern. This study aimed to investigate the genomic characteristics of two strains of oxacillin-resistant and mecA-positive S. haemolyticus isolated from the samples of ear swabs from patients with OM and explore their acquired antibiotic resistance genes (ARGs) and the mobile genetic elements (MGEs). Methods: Two oxacillin-resistant S. haemolyticus strains, isolated from ear swab samples of patients with OM, underwent antimicrobial susceptibility evaluation, followed by whole-genome sequencing. The acquired ARGs and the MGEs carried by the ARGs, harbored by the genomes of two strains of S. haemolyticus were identified. Results: The two strains of oxacillin-resistant S. haemolyticus (strain SH1275 and strain SH9361) both carried the genetic contexts of mecA with high similarity with the SCCmec type V(5C2&5) subtype c. Surprisingly, the chromosomal aminoglycoside resistance gene aac(6')-aph(2") harbored by S. haemolyticus strain SH936 was flanked by two copies of IS256, forming the IS256-element (IS256-GNAT-[aac(6')-aph(2")]-IS256), which was widely present in strains of both Staphylococcus and Enterococcus genus. Furthermore, the two strains of oxacillin-resistant and MDR S. haemolyticus were found to harbor antimicrobial resistance plasmids, including one 26.9-kb plasmid (pSH1275-2) containing msr(A)-mph(C)) and qacA, one mobilizable plasmid pSH1275-3 harboring vga(A)LC, one plasmid (pSH9361-1) carrying erm(C), and one plasmid (pSH9361-2) carrying qacJ. Conclusion: The systematic analysis of whole-genome sequences provided insights into the mobile genetic elements responsible for multi-drug resistance in these two strains of oxacillin-resistant and mecA-positive S. haemolyticus, which will assist clinicians in devising precise, personalized, and clinical therapeutic strategies for treating otitis media caused by multi-drug resistant S. haemolyticus.

Effect of electron beam irradiation on raw goat milk: microbiological, physicochemical and protein structural analysis.

BACKGROUND: Goat milk is considered a nutritionally superior resource, owing to its advantageous nutritional attributes. Nevertheless, it is susceptible to spoilage and the persistence of pathogens. Electron beam irradiation stands as a promising non-thermal processing technique capable of prolonging shelf life with minimal residue and a high degree of automation. RESULTS: The effects of electron beam irradiation (2, 3, 5, and 7 kGy) on microorganisms, physicochemical properties, and protein structure of goat milk compared with conventional pasteurized goat milk (PGM) was evaluated. It was found that a 2 kGy electron beam irradiation reduces the total microbial count of goat milk by 6-logs, and the irradiated goat milk protein secondary structure showed a significant decrease in ɑ-helix content. Low irradiation doses led to microaggregation and crosslinking. In contrast, high doses (≥ 5 kGy) slightly disrupted the aggregates and decreased the particle size, disrupting the microscopic surface structure of goat milk, verified by scanning electron microscopy and confocal laser scanning microscopy. CONCLUSION: The irradiation of goat milk with a 2 kGy electron beam may effectively inactivate harmful microorganisms in the milk and maintain/or improve the physicochemical quality and protein structure of goat milk compared to thermal pasteurization. © 2024 Society of Chemical Industry.

Tuning Pd species via electronic metal-support interaction for methane combustion.

Utilizing catalytic combustion to convert methane (CH4) into CO2 and H2O stands as one of the most effective approaches for mitigating unburnt CH4 emissions from natural gas engines. Supported Pd catalysts have been extensively researched for their role in low-temperature CH4 combustion, with their catalytic activity greatly influenced by metal-support interactions. Surface interaction Pd phases, as a special type of Pd species originating from metal-support interactions on supported Pd catalysts, show controversial catalytic performance in CH4 combustion. Moreover, the impact of electronic metal-support interactions (EMSI, which refers to metal-support interactions associated with electron transfer) remains unclear. Hence, we opted for Ce-Zr solid solutions with different Ce:Zr molar ratios as supports and synthesized a range of supported Pd catalysts with varying EMSI intensities. Characterization revealed that as the oxygen vacancy concentration on the support increased, electron transfer weakened, leading to a higher Pd-O-Ce content, resulting in a lower CH4 activation barrier and better catalytic performance. This study offers a promising approach for regulating EMSI and active Pd species on supported catalysts in practical applications.

Mesenchymal stem cells promote ovarian reconstruction in mice.

BACKGROUND: Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. METHODS: In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. RESULTS: Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. CONCLUSIONS: The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn't proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.

Home Blood Pressure Monitoring and Its Association With Blood Pressure Control Among Hypertensive Patients With High Cardiovascular Risk in China.

Objective: Home blood pressure monitoring (HBPM) is viewed as a facilitating factor in the initial diagnosis and long-term management of treated hypertension. However, evidence remains scarce about the effectiveness of HBPM use in the real world. This study aimed to examine the associations of HBPM use with blood pressure (BP) control and medication adherence. Methods: This prospective cohort study included hypertensive patients with high cardiovascular risk who were aged ≥50 years. At baseline, information about types of BP monitor, frequency of HBPM, perception of anti-hypertensive treatment, and measured office BP were collected. During the 1-year follow-up (visits at 1, 2, 3, 6, and 12 months), information on medication adherence was collected at each visit. The 2 major outcomes were BP control at baseline and medication adherence during the 1-year follow-up. A log-binomial regression model was used to examine the association between frequency of HBPM and outcomes, stratified by the perceptions of anti-hypertensive treatment. Results: A total of 5,363 hypertensive patients were included in the analysis. The age was (64.6 ± 7.2) years, and 41.2% (2,208) were female. Of the total patients, 85.9% (4,606) had a home BP monitor and 47.8% (2,564) had an incorrect perception of anti-hypertensive treatment. Overall, 24.2% (1,299) of patients monitored their BP daily, 37.6% (2,015) weekly, 17.3% (926) monthly, and 20.9% (1,123) less than monthly. At baseline, the systolic BP and diastolic BP were (146.6 ± 10.8) mmHg and (81.9 ± 10.6) mmHg, respectively, and 28.5% (1,527) of patients had their BP controlled. Regardless of whether the patients had correct or incorrect perceptions of anti-hypertensive treatment, there is no significant association between HBPM frequency and BP control at baseline. During the 1-year follow-up, 23.9% (1,280) of patients had non-adherence to medications at least once. In patients with an incorrect perception of anti-hypertensive treatment, those monitoring BP most frequently (daily) had the highest non-adherence rate (29.9%, 175/585). Compared with those monitoring their BP less than monthly, patients who monitored their BP daily were more likely not to adhere to anti-hypertensive medications (adjusted relative risk = 1.38, 95% confidence interval: 1.11-1.72, P = 0.004). Conclusions: HBPM performance among hypertensive patients in China is, in general, sub-optimal. No association was observed between using HBPM alone and hypertension control, indicating that the effects of HBPM could be conditional. Patients' misconceptions about anti-hypertensive treatment may impair the role of BP monitoring in achieving medication adherence. Fully incorporating the correct perception of hypertension into the management of hypertensive patients is needed.

Photocatalytic Generation of H2O2 Via a Hydrogen-Abstraction Pathway by Bi2.15WO6 under Visible Light.

Photocatalytic technology is a popular research area for converting solar energy into environmentally friendly chemicals and is considered the greenest approach for producing H2O2. However, the corresponding reactive oxygen species (ROS) and pathway involved in the photocatalytic generation of H2O2 by the Bi2.15WO6-glucose system are still not clear. Quenching experiments have established that neither •OH nor h+ contribute to the formation of H2O2, and show that the formed surface superoxo (≡Bi-OO•) and peroxo (≡Bi-OOH) species are the predominant ROS in H2O2 generation. In addition, various characterizations indicate the enhanced electron-transfer on the surface of Bi2.15WO6 with increasing contents of glucose via the ligand-to-metal charge transfer pathway, confirming H-transfer from glucose to ≡Bi-OO• or ≡Bi-OOH. The increased production of H2O2 with decreasing bond dissociation energy (BDEO-H) values of various phenolic compounds again supports the H-transfer mechanism from phenolic compounds to ≡Bi-OO• and then to ≡Bi-OOH. DFT calculations further reveal that on the Bi2.15WO6 surface, oxygen is sequentially reduced to ≡Bi-OO• and ≡Bi-OOH, while H-transfer from H2O or glucose to ≡Bi-OO• and ≡Bi-OOH, resulting in the production of H2O2. The lower energy barrier of H-transfer from adsorbed glucose (0.636 eV) than that from H2O (1.157 eV) indicates that H-transfer is more favorable from adsorbed glucose. This work gives new insight into the photocatalytic generation of H2O2 by Bi2.15WO6 in the presence of glucose/phenolic compounds via the H-abstraction pathway.

Construction and validation of an 18F-FDG-PET/CT-based prognostic model to predict progression-free survival in newly diagnosed multiple myeloma patients.

OBJECTIVE: To investigate the relationship between 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) related parameters and the prognosis of multiple myeloma and to establish and validate a prediction model regarding the progression-free survival (PFS) of multiple myeloma. METHODS: A retrospective analysis of 126 newly diagnosed multiple myeloma patients who attended Nanjing Drum Tower Hospital from 2014-2021. All patients underwent PET/CT before treatment and were divided into a training cohort (n = 75) and a validation cohort (n = 51). Multivariate Cox proportional hazard regression analysis incorporated PET/CT-related parameters and clinical indicators. A nomogram was established to individually predict PFS in MM patients. The model was evaluated by calculating the C-index and calibration curve. RESULTS: Here, 4.2 was used as the cut-off value of SUVmax to divide patients into high and low groups. PFS significantly differed between patients in the high-SUVmax group and low-SUVmax group, and SUVmax was an independent predictor of PFS in newly diagnosed multiple myeloma (NDMM) patients. Univariate and multivariate cox regression analysis suggested that lactate dehydrogenase (LDH), bone marrow plasma cell (BMPC), and SUVmax affected PFS. These factors were incorporated to construct a nomogram model for predicting PFS at 1 and 2 years in NDMM patients. The C-index and calibration curves of the nomogram exhibited good accuracy and consistency, and the DCA curves suggested that the model had good clinical utility. CONCLUSION: The PET/CT parameter SUVmax is closely related to the prognosis of myeloma patients. The nomogram constructed in this study based on PET/CT-related parameters and clinical indicators individually predicts the PFS rate of NDMM patients and enables further risk stratification of NDMM patients.

SiW9Co3 @rGO composite-doping improved the crystallization and stability of a perovskite film for efficient photodetection.

The crystalline quality of perovskite films is a key factor that affects the performance of perovskite photovoltaic devices. Polyoxometalates can better match the energy levels of each layer in the devices through their own suitable energy level and band gap, and the good light absorption of POMs can also increase the mobility of photogenerated carriers in the devices. Moreover, POMs with Keggin-type structures can also improve the crystalline quality of perovskite films by eliminating defect sites, which can lead to better crystallization of perovskites with larger grains. In this study, we optimized the crystalline quality of a perovskite layer using the SiW9Co3@rGO composite prepared using POMs and graphene derivatives. XRD and SEM tests show that the crystallization degree of the perovskite layer was improved, the average grain size of which can reach up to 1222.92 nm, which is nearly four times higher than that of a blank perovskite. The photoresponse current of a SiW9Co3@rGO-doped photodetector can reach to 43.94 µA, which is about 226% higher than that of an undoped device. At the same time, the addition of the composite can improve the stability of photodetectors because of the special network structure of graphene. Photodetectors doped with SiW9Co3@rGO can still maintain more than 90% of their high performance for a month. This study proves that POM-based composites have good application prospects in the field of photovoltaic devices.

Potential Impact of Hypoxic Astrocytes on the Aggravation of Depressive Symptoms in Parkinson's Disease.

Mounting evidence suggests a significant correlation between depressive disorders and neurodegenerative conditions, encompassing Alzheimer's disease and Parkinson's disease (PD). Depression represents a substantial non-motor manifestation frequently identified in individuals with PD, posing a significant threat to patients' overall well-being and necessitating the implementation of effective management strategies. Despite its high prevalence, impacting over 40% of PD patients, the precise cellular and molecular mechanisms underlying depression and its relationship to dopaminergic system degeneration remain largely ambiguous. In this study, we presented our findings demonstrating distinct characteristics of cortical astrocytes in PD patients compared to reactivated glial cells in the substantia nigra. We identified a subset of differentially expressed genes associated with depressive disorders from PD-associated cortical astrocytes. Furthermore, we uncovered the potential involvement of the hypoxia signaling in driving cortical astrocytic dysfunctions. Through a comprehensive investigation utilizing transcriptome and chromatin accessibility analyses on cultured human astrocytes, we revealed that hypoxic treatment could induce similar expression changes observed in cortex from PD patients. Additionally, we provided evidence that activation of the HIF-1 signaling pathway suppressed the expression of key components of mitochondrial ribosomes and electron transport chain proteins COX2 and CYTB, resulting in abnormal mitochondrial membrane potential. Our results underscore the potential impact of glial metabolic abnormalities on the development of depressive disorders associated with Parkinson's disease.

Predicting the risk of 1-year mortality among patients hospitalized for acute heart failure in China.

BACKGROUND: We aimed to develop and validate a model to predict 1-year mortality risk among patients hospitalized for acute heart failure (AHF), build a risk score and interpret its application in clinical decision making. METHODS: By using data from China Patient-Centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, which prospectively enrolled patients hospitalized for AHF in 52 hospitals across 20 provinces, we used multivariate Cox proportional hazard model to develop and validate a model to predict 1-year mortality. RESULTS: There were 4,875 patients included in the study, 857 (17.58%) of them died within 1-year following discharge of index hospitalization. A total of 13 predictors were selected to establish the prediction model, including age, medical history of chronic obstructive pulmonary disease and hypertension, systolic blood pressure, Kansas City Cardiomyopathy Questionnaire-12 score, angiotensin converting enzyme inhibitor or angiotensin receptor blocker at discharge, discharge symptom, N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T, serum creatine, albumin, blood urea nitrogen, and highly sensitive C-reactive protein. The model showed a high performance on discrimination (C-index was 0.759 [95% confidence interval: 0.739, 0.778] in development cohort and 0.761 [95% confidence interval: 0.731, 0.791] in validation cohort), accuracy, calibration, and outperformed than several existed risk scores. A point-based risk score was built to stratify low- (0-12), intermediate- (13-16), and high-risk group (≥17) among patients. CONCLUSIONS: A prediction model using readily available predictors was developed and internal validated to predict 1-year mortality risk among patients hospitalized for AHF. It may serve as a useful tool for individual risk stratification and informing decision making to improve clinical care.

Association of cumulative health status with subsequent mortality in patients with acute heart failure.

OBJECTIVE: We aim to examine the association between long-term cumulative health status and subsequent mortality among patients with acute heart failure (HF). METHODS: Based on a national prospective cohort study of patients hospitalized for HF, we measured health status by Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 at 4 time points, i.e. admission, 1-,6- and 12-month after discharge. Cumulative health status was interpreted by cumulative KCCQ-12 score and cumulative times of good health status. Outcomes included subsequent all-cause and cardiovascular mortality. Multivariable Cox proportional hazard models were performed to examine the association between cumulative health status and subsequent mortality. RESULTS: Totally, 2328 patients (36.7% women and median age 66 [IQR: 56-75] years) were included, the median follow-up was 4.34 (IQR: 3.93-4.96) years. Compared with Quartile 4, the lowest Quartile 1 had the highest HR for all-cause mortality (2.96; 95% CI: 2.26-3.87), followed by Quartile 2 (1.79; 95% CI: 1.37-2.34) and Quartile 3 (1.62; 95% CI: 1.23-2.12). Patients with 0-time of good health status had the highest risk of all-cause mortality (HR: 2.41, 95% CI: 1.69-3.46) compared with patients with 4-times of good health status. Similar associations persisted for cardiovascular mortality. CONCLUSIONS: A greater burden of cumulative health status indicated worse survival among patients hospitalized for HF. Repeated KCCQ measurements could be helpful to monitor long-term health status and identify patients vulnerable to death. Clinical Trial Registration: www.clinicaltrials.gov (NCT02878811).

A Comparative Study of Two Radiomics-Based Blood Flow Modes with Thyroid Imaging Reporting and Data System in Predicting Malignancy of Thyroid Nodules and Reducing Unnecessary Fine-Needle Aspiration Rate.

RATIONALE AND OBJECTIVES: We aimed to compare superb microvascular imaging (SMI)-based radiomics methods, and contrast-enhanced ultrasound (CEUS)-based radiomics methods to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for classifying thyroid nodules (TNs) and reducing unnecessary fine-needle aspiration biopsy (FNAB) rate. MATERIALS AND METHODS: This retrospective study enrolled a dataset of 472 pathologically confirmed TNs. Radiomics characteristics were extracted from B-mode ultrasound (BMUS), SMI, and CEUS images, respectively. After eliminating redundant features, four radiomics scores (Rad-scores) were constructed. Using multivariable logistic regression analysis, four radiomics prediction models incorporating Rad-score and corresponding US features were constructed and validated in terms of discrimination, calibration, decision curve analysis, and unnecessary FNAB rate. RESULTS: The diagnostic performance of the BMUS + SMI radiomics method was better than ACR TI-RADS (area under the curve [AUC]: 0.875 vs. 0.689 for the training cohort, 0.879 vs. 0.728 for the validation cohort) (P < 0.05), and comparable with BMUS + CEUS radiomics method (AUC: 0.875 vs. 0.878 for the training cohort, 0.879 vs. 0.865 for the validation cohort) (P > 0.05). Decision curve analysis showed that the BMUS+SMI radiomics method could achieve higher net benefits than the BMUS radiomics method and ACR TI-RADS when the threshold probability was between 0.13 and 0.88 in the entire cohort. When applying the BMUS+SMI radiomics method, the unnecessary FNAB rate reduced from 43.4% to 13.9% in the training cohort and from 45.6% to 18.0% in the validation cohorts in comparison to ACR TI-RADS. CONCLUSION: The dual-modal SMI-based radiomics method is convenient and economical and can be an alternative to the dual-modal CEUS-based radiomics method in helping radiologists select the optimal clinical strategy for TN management.

Protein extraction from chlorella pyrenoidosa microalgae: Green methodologies, functional assessment, and waste stream valorization for bioenergy production.

C. pyrenoidosa, a species of microalgae, has been recognized as a viable protein source for human consumption. The primary challenges in this context are the development of an efficient extraction process and the valorization of the resultant waste streams. This study, situated within the paradigm of circular economy, presents an innovative extraction approach that achieved a protein extraction efficiency of 62 %. The extracted protein exhibited remarkable oil-water emulsifying performances, such as uniform morphology with high creaming stability, suggesting a sustainable alternative to conventional emulsifiers. Additionally, hydrothermal liquefaction technique was employed for converting the residual biomass and waste solution from the extraction process into biocrude. A biocrude yield exceeding 40 wt%, characterized by a carbon content of 73 % and a higher heating value of 36 MJ/kg, were obtained. These findings demonstrate the promising potential of microalgae biorefinery, which is significant for paving toward circular economy and zero-waste society.

A Pt(II) complex bearing N-heterocycle ring induced ferroptotic cell death in ovarian cancer.

Cisplatin is a widely used chemotherapeutic agent which interacts with DNA to form Pt-DNA adducts, leading to DNA double-strand breaks and apoptosis. Resistance is the major obstacle in the clinical application of cisplatin. A quinoline derivative based Pt(II) complex PtQ was synthesized and characterized. As an analogue of cisplatin, PtQ demonstrated a novel anticancer mechanism in ovarian cancer. PtQ caused excessive production of reactive oxygen species (ROS), which triggered ferroptotic cell death in ovarian cancer. Cystine/glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4) which alleviate lipid peroxidation were both downregulated in PtQ-treated SKOV3 cells. Furthermore, PtQ induced DNA single-strand breaks and suppressed the expression of single-strand breaks repair protein PARP1. Mechanism studies demonstrated that PtQ can hopefully bypass the signaling pathways mediated cisplatin resistance in ovarian cancer.

A monofunctional Pt(II) complex combats triple negative breast cancer by triggering lysosome-dependent cell death.

Monofunctional Pt(II) complexes with potent efficacy to overcome the drawbacks of current platinum drugs represent a promising therapeutic approach for triple negative breast cancer (TNBC). A heterocyclic-ligated monofunctional Pt(II) complex PtL with a unique action of mode was designed and investigated. PtL induced DNA single-strand breaks and caused genomic instability in TNBC cells. Mechanism studies demonstrated that PtL disrupted lysosomal acidity and function, which in turn triggered lysosome-dependent cell death. Furthermore, PtL showed convincing suppression in the tube forming and cell migratory abilities against the metastatic potential of TNBC cells. The synthesis and investigation of PtL revealed its potential value as an anti-TNBC drug and extended the family of monofunctional Pt(II) complexes.

The associations of "weekend warrior" and regularly active physical activity with abdominal and general adiposity in US adults.

OBJECTIVE: This study examined the association between physical activity patterns and abdominal and general adiposity. METHODS: Data were extracted among 20- to 59-year-old participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Abdominal and general adiposity was assessed by dual-energy x-ray absorptiometry (DXA) and anthropometric measures. DXA-measured indicators were further normalized into z scores. Physical activity levels were collected by questionnaire and classified as inactive, "weekend warrior" (WW), and regularly active (RA). Survey linear regression models were used to assess associations between physical activity patterns and adiposity indicators. RESULTS: Among 9629 participants, 772 (8.2%) reported the WW pattern and 3277 (36.9%) reported the RA pattern. Compared with inactive, both WW and RA had lower DXA-measured abdominal adiposity (WW: ß: -0.24, 95% CI: -0.38 to -0.10; RA: -0.18, 95% CI: -0.29 to -0.07), waist circumference (WW: ß: -1.94, 95% CI: -3.16 to -0.73; RA: -1.31, 95% CI: -2.32 to -0.29), whole-body fat mass (WW: ß: -0.16, 95% CI: -0.25 to -0.08; RA: -0.11, 95% CI: -0.18 to -0.04), and BMI (WW: ß: -0.78, 95% CI: -1.27 to -0.28; RA: -0.47, 95% CI: -0.89 to -0.04). CONCLUSIONS: The WW pattern was associated with similarly lower abdominal and general adiposity to the RA pattern versus the inactive pattern.

Genomic characteristics and immune landscape of super multiple primary lung cancer.

BACKGROUND: In recent years, a growing number of patients with multiple primary lung cancer (MPLC) are being diagnosed, and a subset of these patients is found to have a large number of lesions at the time of diagnosis, which are referred to as 'super MPLC'. METHODS: Here, we perform whole exome sequencing (WES) and immunohistochemistry (IHC) analysis of PD-L1 and CD8 on 212 tumor samples from 42 patients with super MPLC. FINDINGS: We report the genomic alteration landscape of super MPLC. EGFR, RBM10 and TP53 mutation and TERT amplification are important molecular events in the evolution of super MPLC. We propose the conception of early intrapulmonary metastasis, which exhibits different clinical features from conventional metastasis. The IHC analyses of PD-L1 and CD8 reveal a less inflamed microenvironment of super MPLC than that of traditional non-small cell lung cancer (NSCLC). We identify the potentially susceptible germline mutations for super MPLC. INTERPRETATION: Our study depicts the genomic characteristics and immune landscape, providing insights into the pathogenesis and possible therapeutic guidance of super MPLC. FUNDING: A full list of funding bodies that supported this study can be found in the Acknowledgements section.

Nanomaterials in Medicine: Understanding Cellular Uptake, Localization, and Retention for Enhanced Disease Diagnosis and Therapy.

Nanomaterials (NMs) have emerged as promising tools for disease diagnosis and therapy due to their unique physicochemical properties. To maximize the effectiveness and design of NMs-based medical applications, it is essential to comprehend the complex mechanisms of cellular uptake, subcellular localization, and cellular retention. This review illuminates the various pathways that NMs take to get from the extracellular environment to certain intracellular compartments by investigating the various mechanisms that underlie their interaction with cells. The cellular uptake of NMs involves complex interactions with cell membranes, encompassing endocytosis, phagocytosis, and other active transport mechanisms. Unique uptake patterns across cell types highlight the necessity for customized NMs designs. After internalization, NMs move through a variety of intracellular routes that affect where they are located subcellularly. Understanding these pathways is pivotal for enhancing the targeted delivery of therapeutic agents and imaging probes. Furthermore, the cellular retention of NMs plays a critical role in sustained therapeutic efficacy and long-term imaging capabilities. Factors influencing cellular retention include nanoparticle size, surface chemistry, and the cellular microenvironment. Strategies for prolonging cellular retention are discussed, including surface modifications and encapsulation techniques. In conclusion, a comprehensive understanding of the mechanisms governing cellular uptake, subcellular localization, and cellular retention of NMs is essential for advancing their application in disease diagnosis and therapy. This review provides insights into the intricate interplay between NMs and biological systems, offering a foundation for the rational design of next-generation nanomedicines.

MARVEL family proteins contribute to vegetative growth, development, and virulence of the insect fungal pathogen Beauveria bassiana.

Beauveria bassiana is one of the most extensively studied entomopathogenic fungi (EPF) and is widely used as a biocontrol agent against various insect pests. Proteins containing the MARVEL domain are conserved in eukaryotes, typically with four transmembrane structures. In this study, we identified the five MARVEL domain proteins in B. bassiana. Five MARVEL domain proteins were localized to cytomembrane and vacuoles in B. bassiana, but had different roles in maintaining the lipid-droplet homeostasis. These proteins were required for fungal virulence, but differentially contributed to fungal utilization of nutrients, stress tolerance, and development under aerial and submerged conditions. Notably, BbMARVEL2 was essential for conidial surface morphology. Additionally, these five MARVEL domain proteins contributed to fungal interaction with the host immune defense. This study provides new mechanistic insights into the life cycle of B. bassiana as a biocontrol agent.