Biomimetic Electrodynamic Metal-Organic Framework Nanosponges for Augmented Treatment of Biofilm Infections.

Electrodynamic therapy (EDT) is a promising alternative approach for antibacterial therapy, as reactive oxygen species (ROS) are produced efficiently in response to an electric field without relying on endogenous H2O2 and O2. However, the inherent toxicity of metallic catalysts and numerous bacterial toxins during the therapeutic process still hinder its development. Herein, biomimetic metal-organic (MOF@EV) nanosponges composed of ginger-derived extracellular vesicles (EVs), and electrodynamic metal-organic frameworks (MOFs) are developed for the eradication of bacterial infections and the absorption of toxins. The prolonged circulation time of MOF@EV in vivo facilitates their accumulation at infection sites. More interestingly, MOF@EV can behave as nanosponges and effectively prevent host cells from binding to bacterial toxins, thereby reducing damage to cells. Subsequently, the MOF@EV nanosponges are discovered to work as electro-sensitizers, which is confirmed through both theoretical calculation and experimental verification. As a result, ROS is continuously produced under the electric field to achieve effective EDT-mediated bacterial eradication. Meanwhile, the treatment process of MOF@EV in vivo is visualized in mice infected with luciferase-expressing Staphylococcus aureus (S. aureus), and excellent biofilm eradication capacity and detoxification efficiency are demonstrated in a subcutaneous abscess model. This work provides a promising strategy for the treatment of bacterial infections.

Adverse pregnancy outcomes and multiple cancers risk in both mother and offspring: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring. METHODS: PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544). RESULTS: The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02-1.12), prostate cancer (OR = 1.02, 95% CI = 1.00-1.05), leukemia (OR = 1.18, 95% CI = 1.13-1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12-1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16-6.71); and a linear dose-response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09-1.24), respectively. CONCLUSIONS: Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility.

Cationized Decalcified Bone Matrix for Infected Bone Defect Treatment.

Objective: We aim to develop a dual-functional bone regeneration scaffold (Qx-D) with antibacterial and osteogenic properties for infected bone defect treatment. Impact Statement: This study provides insights into antibacterial components that could be combined with naturally derived materials through a facile Schiff base reaction, offering a potential strategy to enhance antibacterial properties. Introduction: Naturally derived decalcified bone matrix (DBM) has been reported to be porous and biodegradable. DBM can induce various cell differentiations and participate in immune regulation, making it an ideal bone regeneration scaffold for bone defects. However, DBM does not exhibit antimicrobial properties. Therefore, it is essential to develop antibacterial functionalization method for DBM. Methods: DBM was modified with a macromolecular quaternary ammonium salt (QPEI). A series of Qx-D with tunable feeding ratios were synthesized through Schiff base reaction. The morphology, chemical property, in vitro antibacterial efficiency, in vitro biocompatibility, osteogenic property, and in vivo anti-infection performances were characterized. Results: All Qx-D exhibited marked antibacterial properties. Small adjustments in feed concentration could not induce changes in antibacterial properties. However, cell viability slightly decreased with increasing feed concentration. Q10-D demonstrated significant antibacterial properties and could promote recovery of infected bone defect in an animal model. Conclusion: Qx-D shows marked antibacterial properties and good biocompatibility. Moreover, Q10-D could be a potential choice for infected bone defects.

Intestinal Lactobacillus murinus-derived small RNAs target porcine polyamine metabolism.

Gut microbiota plays a vital role in host metabolism; however, the influence of gut microbes on polyamine metabolism is unknown. Here, we found germ-free models possess elevated polyamine levels in the colon. Mechanistically, intestinal Lactobacillus murinus-derived small RNAs in extracellular vesicles down-regulate host polyamine metabolism by targeting the expression of enzymes in polyamine metabolism. In addition, Lactobacillus murinus delays recovery of dextran sodium sulfate-induced colitis by reducing polyamine levels in mice. Notably, a decline in the abundance of small RNAs was observed in the colon of mice with colorectal cancer (CRC) and human CRC specimens, accompanied by elevated polyamine levels. Collectively, our study identifies a specific underlying mechanism used by intestinal microbiota to modulate host polyamine metabolism, which provides potential intervention for the treatment of polyamine-associated diseases.

An NIR-responsive hydrogel loaded with polydeoxyribonucleotide nano-vectors for enhanced chronic wound healing.

Chronic diabetic wounds are difficult to treat due to imbalanced inflammatory responses, high blood glucose levels, and bacterial infections. Novel therapeutic approaches based on nucleic acid analogues have been proposed, with unique advantages in improving angiogenesis, increasing collagen synthesis, and exerting anti-inflammatory effects. However, the inherent electronegativity of nucleic acids makes them less susceptible to cellular uptake. In this paper, a kind of near infrared (NIR)-responsive nanocomposite hydrogel loaded with nucleic acid vectors was proposed for promoting wound healing. The redox system composed of molybdenum disulphide nanosheets (MoS2 NSs) initiated the copolymerization of quaternized chitosan containing double bonds and N-isopropylacrylamide (NIPAAm) to form the matrix. In addition, MoS2 NSs with photothermal conversion performance endow the nanocomposite hydrogel to have NIR-response property and act as physical crosslinking points in the matrix. Polydeoxyribonucleotides (PDRN), which have the effect of promoting wound healing, were made into nucleic acid vectors, and loaded into the NIR-responsive hydrogel. MoS2 NSs can convert NIR irradiation into heat, causing phase transitions of temperature-sensitive segments that trigger volume contraction of the hydrogel to extrude the nucleic acid vector. Promoting angiogenesis, slowing inflammation, and guiding tissue regeneration were demonstrated in the diabetic wound model treated with the NIR-responsive nanocomposite hydrogel.

Optimal fasting duration for mice as assessed by metabolic status.

In the study of obesity and diabetes, mice are widely used for experimental research, and fasting is a common procedure used to reset metabolism in mouse models. The fasting duration for experimental mice varies greatly in nutritional and metabolic studies, ranging from 2 to 48 h. This study aims to assess the optimal fasting duration for mice fed low- and high-fat diets over a short period of time. C57BL/6J mice were fed a low-fat diet (LFD) or high-fat diet (HFD) and fasted for 4, 6, 8, 10, 12, or 24 h. The effects of different conditions after fasting on the metabolic level of mice were explored, and the data were collected for analysis. Our data indicate that fasting has inconsistent effects on mice fed a low-fat or high-fat diet. To compare the metabolic differences between mice in different dietary levels and thereby secure better scientific data, mice should fast for 6 h in animal experiments. Fasting for 6 h is also recommended when comparing glucose tolerance with insulin tolerance.

Triboelectric Nanogenerator Made with Stretchable, Antibacterial Hydrogel Electrodes for Biomechanical Sensing.

Triboelectric nanogenerators (TENGs) have attracted widespread attention as a promising candidate for energy harvesting due to their flexibility and high power density. To meet diverse application scenarios, a highly stretchable (349%), conductive (1.87 S m-1), and antibacterial electrode composed of carbon quantum dots/LiCl/agar-polyacrylamide (CQDs/LiCl/agar-PAAm) dual-network (DN) hydrogel is developed for wearable TENGs. Notably, the concentration of agar alters the pore spacing and pore size of the DN hydrogel, thereby impacting the network cross-linking density and the migration of conductive ions (Li+ and Cl-). This variation further affects the mechanical strength and conductivity of the hydrogel electrode, thus modulating the mechanical stability and electrical output performance of the TENGs. With the optimal agar content, the tensile strength and conductivity of the hydrogel electrode increase by 211 and 719%, respectively. This enhancement ensures the stable output of TENGs during continuous operation (6000 cycles), with open-circuit voltage, short-circuit current, and transferred charge increasing by 200, 530, and 155%, respectively. Additionally, doping with CQDs enables the hydrogel electrode to effectively inhibit the Gram-negative bacterium Escherichia coli. Finally, the TENGs are utilized as a self-power smart ring for efficient and concise information transmission via Morse code. Consequently, this study introduces a creative approach for designing and implementing multifunctional, flexible wearable devices.

Stereotactic body radiotherapy with sequential tislelizumab and chemotherapy as neoadjuvant therapy in patients with resectable non-small-cell lung cancer in China (SACTION01): a single-arm, single-centre, phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy with chemotherapy improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Given its immunomodulating effect, we investigated whether stereotactic body radiotherapy (SBRT) enhances the effect of immunochemotherapy. METHODS: The SACTION01 study was a single-arm, open-label, phase 2 trial that recruited patients who were 18 years or older and had resectable stage IIA-IIIB NSCLC from the Sun Yat-sen University Cancer Center, Guangzhou, China. Eligible patients received SBRT (24 Gy in three fractions) to the primary tumour followed by two cycles of 200 mg intravenous PD-1 inhibitor, tislelizumab, plus platinum-based chemotherapy. Surgical resection was performed 4-6 weeks after neoadjuvant treatment. The primary endpoint was major pathological response (MPR), defined as no more than 10% residual viable tumour in the resected tumour. All analyses were conducted on an intention-to-treat basis, including all patients who were scheduled for neoadjuvant treatment. The trial was registered with ClinicalTrials.gov (NCT05319574) and is ongoing but closed to recruitment. FINDINGS: Between May 18, 2022, and June 20, 2023, 46 patients (42 men and four women) were enrolled and scheduled for neoadjuvant treatment. MPR was observed in 35 (76%, 95% CI 61-87) of 46 patients. The second cycle of immunochemotherapy was withheld in four (9%) patients due to pneumonia (n=2), colitis (n=1), and increased creatinine (n=1). Grade 3 or worse adverse events related to neoadjuvant treatment occurred in 12 (26%, 95% CI 14-41) patients. The most frequent treatment-related adverse event (TRAE) was alopecia (16 [35%] patients), and the most frequent grade 3 or worse TRAE was neutropenia (six [13%]). There was one treatment-related death, caused by neutropenia. No deaths within 90 days of surgery were reported. INTERPRETATION: Preoperative SBRT followed by immunochemotherapy is well tolerated, feasible, and leads to a clinically significant MPR rate. Future randomised trials are warranted to support these findings. FUNDING: BeiGene.

Prediction of acute onset of chronic cor pulmonale: comparative analysis of Holt-Winters exponential smoothing and ARIMA model.

BACKGROUND: The aim of this study is to analyze the trend of acute onset of chronic cor pulmonale at Chenggong Hospital of Kunming Yan'an Hospital between January 2018 and December 2022.Additionally, the study will compare the application of the ARIMA model and Holt-Winters model in predicting the number of chronic cor pulmonale cases. METHODS: The data on chronic cor pulmonale cases from 2018 to 2022 were collected from the electronic medical records system of Chenggong Hospital of Kunming Yan'an Hospital. The ARIMA and Holt-Winters models were constructed using monthly case numbers from January 2018 to December 2022 as training data. The performance of the model was tested using the monthly number of cases from January 2023 to December 2023 as the test set. RESULTS: The number of acute onset of chronic cor pulmonale in Chenggong Hospital of Kunming Yan'an Hospital exhibited a downward trend overall from 2018 to 2022. There were more cases in winter and spring, with peaks observed in November to December and January of the following year. The optimal ARIMA model was determined to be ARIMA (0,1,1) (0,1,1)12, while for the Holt-Winters model, the optimal choice was the Holt-Winters multiplicative model. It was found that the Holt-Winters multiplicative model yielded the lowest error. CONCLUSION: The Holt-Winters multiplicative model predicts better accuracy. The diagnosis of acute onset of chronic cor pulmonale is related to many risk factors, therefore, when using temporal models to fit and predict the data, we must consider such factors' influence and try to incorporate them into the models.

Rapid and equipment-free identification of papaya mealybug Paracoccus marginatus based on RPA-CRISPR/Cas12a.

BACKGROUND: Paracoccus marginatus has invaded many countries, spreading rapidly and causing significant economic losses to crops. Accurate detection during the monitoring process is critical to prevent its expansion into new areas, therefore it is necessary to develop efficient and reliable detection methods. Traditional detection methods are time-consuming and instrument-dependent owing to the morphological similarities and small sizes of P. marginatus and other mealybugs, therefore establishing an efficient, rapid, and sensitive method for field detection in resource-limited settings is critical. RESULTS: A sensitive and rapid detection system was developed to detect P. marginatus using recombinase polymerase amplification (RPA) combined with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a. The RPA-CRISPR/Cas12a assay distinguished P. marginatus from 10 other mealybugs. The entire process can be completed in approximately an hour, and the identification results can be determined by the naked eye using lateral flow strips or a portable mini-UV torch. A method was developed to extract DNA from P. marginatus within 5 min. This method was combined with the RPA-CRISPR/Cas12a assay to achieve rapid and simple detection. In addition, two portable thermos cups with temperature displays were used to maintain the reagents and assay reactions in the field. CONCLUSION: This assay represents the first application of portable and easily available items (mini-UV torch and thermos cup) based on the combination of RPA and CRISPR/Cas12a for rapid pest detection. This method is rapid, highly specific, and instrument-flexible, allowing for the early monitoring of P. marginatus in the field. This study provides guidance for the development of suitable management strategies. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

[Screening of Characteristic Pollutants and Risk Pollutants in Different Media in the Yangtze River Basin Using Comprehensive Evaluation and Risk Quotient Methods].

A variety of pollutants have frequently been detected in the Yangtze River Basin with the rapid economic development, the population increase, and the acceleration of urbanization, which threaten the aquatic ecosystem and human health. A multi-criteria comprehensive evaluation method was developed to identify the characteristic pollutants, and the risk quotient method was used to derive the risk pollutants in water and sediment samples in this article. A total of 155 pollutants from 11 categories were detected in the Yangtze River Basin according to the literature research. Then, the K-means method was used to analyze the cluster of pollutant comprehensive scores. All pollutants were graded based on their scores and recorded as Ⅰ-Ⅵ according to the number of cases in each cluster. A total of 43 pollutants with high scores of Ⅰ and Ⅱ were listed as the characteristic pollutants, which included 11 polycyclic aromatic hydrocarbons, 11 organochlorine pesticides, 10 polychlorinated biphenyls, eight dioxins, two heavy metals, and one phthalate ester. The top five median concentrations of contaminants in water and sediment samples were heavy metals, polycyclic aromatic hydrocarbons, phthalates esters, bisphenols, and pharmaceuticals and personal care products. According to the principle of risk maximization, the risk entropy value （RQ） was calculated based on the highest pollutant concentration. A total of 38 risky pollutants were screened in the water samples （RQ ≥ 0.1）. There were eight high-risk pollutants with RQ ≥ 1, which included benzo[a,h]-anthracene, anthracene, benzo[a]anthracene, pyrene, methoxychlor, aldrin, 2,4'-dichlorodiphenyl, and cadmium. There were 15 high-risk contaminants in the sediment, which included benzo[b]fluoranthene, anthracene, acenaphthene, fluoranthene, cadmium, lead, chromium, arsenic, selenium, dibutyl phthalate, dimethyl phthalate, diisobutyl phthalate, norfloxacin, perfluorobutyric acid, and bisphenol A. The risk pollutants contained emerging pollutants, which included ten pollutants in water samples and nine pollutants in sediments. Antibiotic pollutants accounted for the largest proportion of these emerging pollutants. The information provided in this article may be useful for the relevant departments to monitor the pollutants and propose management programs for the Yangtze River Basin. Additionally, it is of great significance for the ecological environmental protection and management of the Yangtze River Basin.

Rodent model of metabolic dysfunction-associated fatty liver disease: a systematic review.

Although significant progress has been made in developing preclinical models for metabolic dysfunction-associated steatotic liver disease (MASLD), few have encapsulated the essential biological and clinical outcome elements reflective of the human condition. We conducted a comprehensive literature review of English-language original research articles published from 1990 to 2023, sourced from PubMed, Embase, and Web of Science, aiming to collate studies that provided a comparative analysis of physiological, metabolic, and hepatic histological characteristics between MASLD models and control groups. The establishment of a robust metabolic dysfunction-associated steatotic liver rodent model hinges on various factors, including animal species and strains, sex, induction agents and methodologies, and the duration of induction. Through this review, we aim to guide researchers in selecting suitable induction methods and animal species for constructing preclinical models aligned with their specific research objectives and laboratory conditions. Future studies should strive to develop simple, reliable, and reproducible models, considering the model's sensitivity to factors such as light-dark cycles, housing conditions, and environmental temperature. Additionally, the potential of diverse in vitro models, including 3D models and liver organ technology, warrants further exploration as valuable tools for unraveling the cellular mechanisms underlying fatty liver disease.

Molecular dynamics simulation of DNAN/DNB cocrystal PBXs.

CONTEXT: The DNAN/DNB eutectic is a high-energy explosive eutectic with superior safety and thermal stability compared to traditional melt-cast explosives. However, the addition of polymer binders can effectively enhance its mechanical properties, allowing for continued production demands without the need for changes to existing factory equipment. In this paper, a model of the DNAN/DNB eutectic explosive was established, and five different types of polymers-cis-1,4-polybutadiene (BR), ethylene-vinyl acetate copolymer (EVA), polyethylene glycol (PEG), fluorinated polymer (F2603), and polyvinylidene fluoride (PVDF)-were added to the (1 0 - 1), (1 0 1), and (0 1 1) cleavage planes, respectively, to form polymer-bonded explosives (PBXs). The stability, trigger bond length, mechanical properties, and detonation performance of the various polymer-bound PBXs were predicted retrogressively. Among the five PBX models, the DNAN/DNB/PEG model exhibited the highest binding energy and the shortest trigger bond length, indicating a significant improvement in stability, compatibility, and sensitivity compared to the original eutectic. Additionally, although the detonation performance of DNAN/DNB decreased after the addition of binders, the final results were still satisfactory. Overall, the DNAN/DNB/PEG model demonstrated excellent comprehensive performance, proving that among the many polymer binders, PEG is the optimal choice for DNAN/DNB. METHODS: Within the Materials Studio software, molecular dynamics (MD) simulations were employed to predict the properties of the DNAN/DNB eutectic PBX. The MD simulation timestep was set to 1 fs, with a cumulative simulation duration of 2 ns. A 2 ns MD simulation was conducted using the isothermal-isobaric ensemble (NPT). The COMPASS force field was applied, and the temperature was fixed at 295 K.

NIR-II-Responsive Hybrid System Achieves Cascade-Augmented Antitumor Immunity via Genetic Engineering of Both Bacteria and Tumor Cells.

The combination of nanoparticles and tumor-targeting bacteria for cancer immunotherapy can overcome the shortcomings of poor nanoparticle accumulation, limited penetration, and restricted distribution. However, it remains a great challenge for the hybrid system to improve therapeutic efficacy through the simultaneous and controllable regulation of immune cells and tumor cells. Herein, a hybrid therapeutic platform is rationally designed to achieve immune cascade-augmented cancer immunotherapy. To construct the hybrids, photothermal nanoparticles responsive to light in the second near-infrared (NIR-II) region are conjugated onto the surface of engineered bacteria through pH-responsive Schiff base bonds. Taking advantage of the hypoxia targeting and deep penetration characteristics of the bacteria, the hybrids can accumulate at tumor sites. Then nanoparticles detach from the bacteria to realize genetic engineering of tumor cells, which induces tumor cell apoptosis and down-regulate the expression of programmed cell death ligand 1 to alleviate immunosuppressive tumor microenvironment. The mild photothermal heating can not only induce tumor-associated antigen release, but also trigger sustainable expression of cytokine interleukin-2. Notably, a synergistic antitumor effect is achieved between the process of p53 transfection and NIR-II light-activated genetic engineering of bacteria. This work proposes a facile strategy for the construction of hybrid system to achieve cascade-augmented cancer immunotherapy.

A bibliometric analysis of anxiety and depression among primary school students.

Background: Rising anxiety and depression in primary school students adversely affect their development and academics, burdening families and schools. This trend necessitates urgent, focused research within this young demographic. This alarming trend calls for a systematic bibliometric analysis to develop effective preventative and remedial strategies. Objectives: This study aims to identify and analyze the prevailing research hotspots and emerging trends concerning anxiety and depression in primary school students, thereby furnishing a foundational reference for future academic endeavors in this area. Methods: This study uses the Web of Science (WOS) Core Collection database as the data source, focusing on literature published between 2013 and 2023 concerning anxiety and depression in primary school students. An initial search identified 1852 articles, which were then manually screened to exclude duplicates, conferences, announcements, and unrelated literature, resulting in 1791 relevant articles. The analysis, executed on December 31, 2023, employed CiteSpace and Vosviewer tools to assess various bibliometric indicators including authorship, country, institutional affiliations, publication trends, keyword frequency, and citation analysis. Results: The analysis revealed a corpus of 1,791 English-language articles, with a discernible upward trend in publications over the decade. The USA and China were the leading countries in this field, with 482and 272 papers, respectively. The research predominantly addresses the etiological factors of anxiety and depression, various intervention strategies, and the comorbidities associated with these conditions in the target population. Key research focuses have been identified in areas such as suicidal thoughts, bullying in schools, the impact of COVID-19, mindfulness interventions, and anxiety related to mathematics. Future research is projected to increasingly focus on the effects of mathematics anxiety on the psychological and behavioral outcomes in students. Conclusion: This study provides a critical visual and analytical overview of the key research areas and trends in the field of anxiety and depression among primary school students. It underscores the necessity of concentrating on the underlying causes and potential interventions. Such focused research is imperative for mitigating the mental health challenges faced by young students and enhancing their educational and developmental outcomes.

A highly polarizable concentrated dipole glass for ultrahigh energy storage.

Relaxor ferroelectrics are highly desired for pulse-power dielectric capacitors, however it has become a bottleneck that substantial enhancements of energy density generally sacrifice energy efficiency under superhigh fields. Here, we demonstrate a novel concept of highly polarizable concentrated dipole glass in delicately-designed high-entropy (Bi1/3Ba1/3Na1/3)(Fe2/9Ti5/9Nb2/9)O3 ceramic achieved via substitution of multiple heterovalent ferroelectric-active principal cation species on equivalent lattice sites. The atomic-scaled polar heterogeneity of dipoles with different polar vectors between adjacent unit cells enables diffuse reorientation process but disables appreciable growth with electric fields. These unique features cause superior recoverable energy density of ~15.9 J cm-3 and efficiency of ~93.3% in bulk ceramics. We also extend the highly polarizable concentrated dipole glass to the prototype multilayer ceramic capacitor, which exhibits record-breaking recoverable energy density of ~26.3 J cm-3 and efficiency of ~92.4% with excellent temperature and cycle stability. This research presents a distinctive approach for designing high-performance energy-storage dielectric capacitors.

In vivo proximity proteomics uncovers palmdelphin (PALMD) as a Z-disc-associated mitigator of isoproterenol-induced cardiac injury.

Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis.

Investigating the mechanism of tricyclic decyl benzoxazole -induced apoptosis in liver Cancer cells through p300-mediated FOXO3 activation.

OBJECTIVE: To investigate whether tricyclic decylbenzoxazole (TDB) regulates liver cancer cell proliferation and apoptosis through p300-mediated FOXO acetylation. METHODS: Sequencing, adenovirus, and lentivirus transfection were performed in human liver cancer cell line SMMC-7721 and apoptosis was detected by Tunel, Hoechst, and flow cytometry. TEM for mitochondrial morphology, MTT for cell proliferation ability, Western blot, and PCR were used to detect protein levels and mRNA changes. RESULTS: Sequencing analysis and cell experiments confirmed that TDB can promote the up-regulation of FOXO3 expression. TDB induced FOXO3 up-regulation in a dose-dependent manner, promoted the expression of p300 and Bim, and enhanced the acetylation and dephosphorylation of FOXO3, thus promoting apoptosis. p300 promotes apoptosis of cancer cells through Bim and other proteins, while HAT enhances the phosphorylation of FOXO3 and inhibits apoptosis. Overexpression of FOXO3 can increase the expression of exo-apoptotic pathways (FasL, TRAIL), endo-apoptotic pathways (Bim), and acetylation at the protein level and inhibit cell proliferation and apoptotic ability, while FOXO3 silencing or p300 mutation can partially reverse apoptosis. In tumor tissues with overexpression of FOXO3, TDB intervention can further increase the expression of p53 and caspase-9 proteins in tumor cells, resulting in loss of mitochondrial membrane integrity during apoptosis, the release of cytoplasm during signal transduction, activation of caspase-9 and synergistic inhibition of growth. CONCLUSION: TDB induces proliferation inhibition and promotes apoptosis of SMMC-7721 cells by activating p300-mediated FOXO3 acetylation.

Changes in the recent three decades and survey on the current status of surgical treatment for esophageal cancer in China.

BACKGROUND: To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. METHODS: We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. RESULTS: A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. CONCLUSIONS: Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

Improved Cell Adhesion on Self-Assembled Chiral Nematic Cellulose Nanocrystal Films.

Chirality is ubiquitous in nature, and closely related to biological phenomena. Nature-originated nanomaterials such as cellulose nanocrystals (CNCs) are able to self-assemble into hierarchical chiral nematic CNC films and impart handedness to nano and micro scale. However, the effects of the chiral nematic surfaces on cell adhesion are still unknown. Herein, this work presents evidence that the left-handed self-assembled chiral nematic CNC films (L-CNC) significantly improve the adhesion of L929 fibroblasts compared to randomly arranged isotropic CNC films (I-CNC). The fluidic force microscopy-based single-cell force spectroscopy is introduced to assess the cell adhesion forces on the substrates of L-CNC and I-CNC, respectively. With this method, a maximum adhesion force of 133.2 nN is quantified for mature L929 fibroblasts after culturing for 24 h on L-CNC, whereas the L929 fibroblasts exert a maximum adhesion force of 78.4 nN on I-CNC under the same condition. Moreover, the instant SCFS reveals that the integrin pathways are involved in sensing the chirality of substrate surfaces. Overall, this work offers a starting point for the regulation of cell adhesion via the self-assembled nano and micro architecture of chiral nematic CNC films, with potential practical applications in tissue engineering and regenerative medicine.