Disorder-Broadened Phase Boundary with Enhanced Amorphous Superconductivity in Pressurized In2Te5.

As an empirical tool in materials science and engineering, the iconic phase diagram owes its robustness and practicality to the topological characteristics rooted in the celebrated Gibbs phase law (F = C - P + 2). When crossing the phase diagram boundary, the structure transition occurs abruptly, bringing about an instantaneous change in physical properties and limited controllability on the boundaries (F = 1). Here, we expand the sharp phase boundary to an amorphous transition region (F = 2) by partially disrupting the long-range translational symmetry, leading to a sequential crystalline-amorphous-crystalline (CAC) transition in a pressurized In2Te5 single crystal. Through detailed in-situ synchrotron diffraction, we elucidate that the phase transition stems from the rotation of immobile blocks [In2Te2]2+, linked by hinge-like [Te3]2- trimers. Remarkably, within the amorphous region, the amorphous phase demonstrates a notable 25% increase of the superconducting transition temperature (Tc), while the carrier concentration remains relatively constant. Furthermore, we propose a theoretical framework revealing that the unconventional boost in amorphous superconductivity might be attributed to an intensified electron correlation, triggered by a disorder-augmented multifractal behavior. These findings underscore the potential of disorder and prompt further exploration of unforeseen phenomena on the phase boundaries. This article is protected by copyright. All rights reserved.

Asymmetric Tandem Michael Addition/Interrupted Nef Reactions of Nitromethane with Oxindole-Derived Alkenes: Enantioselective Synthesis of Spiro-polycyclic Oxindoles.

Chiral spiro-polycyclic oxindoles are valuable heterocyclic ring systems that are widely distributed in natural alkaloids and biologically active compounds. Herein, we reported an asymmetric tandem Michael addition/interrupted Nef reaction of nitromethane with oxindole-derived alkenes catalyzed by a chiral 2-aminobenzimidazole bifunctional organocatalyst. A series of novel enantiomerically enriched spiro-polycyclic oxindole derivatives bearing an oxime group were synthesized in moderate to excellent isolated yields (up to 99%) with an excellent level of enantioselectivities (up to 99% ee). Furthermore, the antiproliferation activity of the resulting oxindoles derivatives were evaluated, and compound 2d demonstrated promising anticancer properties against HCT116 (IC50 = 14.08 µM) and HT29 (IC50 = 15.46 µM) cell lines.

Safety and Efficacy of Erbium: Yttrium-Aluminum-Garnet Laser Treatment in Chinese Women with Mild-to-Moderate Stress Urinary Incontinence.

Background: This study aims to evaluate the safety and efficacy of erbium:yttrium-aluminum-garnet (Er:YAG) laser treatment in female patients with mild-to-moderate stress urinary incontinence (SUI). Methods: From July 2018 to June 2020, 72 female patients with mild-to-moderate SUI were enrolled in this study. A baseline assessment was conducted, which included a 1-hour pad test, the validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), postvoid residual (PVR) testing, pelvic organ prolapse quantification (POP-Q) testing, and a cough stress test. All patients underwent four sessions of Er:YAG laser treatment using a smooth mode. A reassessment was performed 6 months after treatment to evaluate the safety and efficacy of the Er:YAG laser. Results: All patients completed four clinic visits, with a 1-month interval, and were followed up for a minimum of 6 months. No severe adverse reactions were observed during the treatment process. The 1-hour pad test revealed a significant reduction in urinary leakage from baseline (6.30 ± 1.06 g) to the 6-month follow-up (2.70 ± 0.96 g, p < 0.001), with 34 of 72 (47.22%) patients achieving negative results. The ICIQ-UI-SF score significantly decreased from baseline to 6 months (10.82 ± 1.38 to 2.96 ± 0.52, p < 0.001). PVR experimental results showed a significant decrease in residual urine volume after treatment (103.72 ± 8.61 mL to 43.86 ± 4.92 mL, p < 0.001). At the 6-month follow-up, hematoxylin and eosin staining results demonstrated that Er:YAG laser treatment significantly facilitated an increase in the thickness of squamous epithelial cells. The efficacy of Er:YAG laser treatment for SUI was 77.78% (56/72). Conclusions: Several objective and subjective assessments confirmed the safety and efficacy of vaginal smooth mode Er:YAG laser treatment for mild-to-moderate SUI during the 6-month follow-up period. Nonablative Er:YAG laser in the smooth mode is a viable treatment option for SUI patients.

IGF-1 Induces Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells by Promoting SOX4 via the MAPK/ERK Pathway.

Tissue engineering envisions functional substitute creation for damaged tissues. Insulin-like growth factor-1 (IGF-1) plays roles in bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation (OD), and we investigated its specific mechanism. BMSCs were cultured and OD was induced. Surface antigens (CD105, CD90, CD44, CD45, CD34) were identified by flow cytometry. Adipogenic, chondrogenic, and osteogenic differentiation abilities of BMSCs were observed. BMSCs were cultured in osteogenic medium containing 80 ng/mL IGF-1 for 3 weeks. Alkaline phosphatase activity, calcification level, osteogenic factor (runt related protein 2 [RUNX2], osteocalcin [OCN], osterix [OSX]), total (t-) ERK1/2 and phosphorylated- (p-) ERK1/2 levels, and SRY-related high-mobility-group box 4 (SOX4) levels were assessed by alkaline phosphatase staining and Alizarin Red staining, Western blot, and reverse transcription-quantitative polymerase chain reaction. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway inhibitor (PD98059) was used to inhibit the MAPK/ERK pathway in IGF-1-treated BMSCs. Small interfering-SOX4 was transfected into BMSCs to down-regulate SOX4. IGF-1 increased alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels in BMSCs, indicating that IGF-1 induced rat BMSC OD. SOX4, and p-ERK1/2 and t-ERK1/2 levels were elevated in IGF-1-induced BMSCs, which were annulled by PD98059. PD98059 partly averted IGF-1-induced rat BMSC OD. SOX4 levels, alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels were reduced after SOX4 down-regulation, showing that downregulation of SOX4 averted the effect of IGF-1 on inducing rat BMSC OD. IGF-1 induced rat BMSC OD by stimulating SOX4 via the MAPK/ERK pathway.

Self-assembly of PEG-PPS polymers and LL-37 peptide nanomicelles improves the oxidative microenvironment and promotes angiogenesis to facilitate chronic wound healing.

Refractory diabetic wounds are associated with high incidence, mortality, and recurrence rates and are a devastating and rapidly growing clinical problem. However, treating these wounds is difficult owing to uncontrolled inflammatory microenvironments and defective angiogenesis in the affected areas, with no established effective treatment to the best of our knowledge. Herein, we optimized a dual functional therapeutic agent based on the assembly of LL-37 peptides and diblock copolymer poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS). The incorporation of PEG-PPS enabled responsive or controlled LL-37 peptide release in the presence of reactive oxygen species (ROS). LL-37@PEG-PPS nanomicelles not only scavenged excessive ROS to improve the microenvironment for angiogenesis but also released LL-37 peptides and protected them from degradation, thereby robustly increasing angiogenesis. Diabetic wounds treated with LL-37@PEG-PPS exhibited accelerated and high-quality wound healing in vivo. This study shows that LL-37@PEG-PPS can restore beneficial angiogenesis in the wound microenvironment by continuously providing angiogenesis-promoting signals. Thus, it may be a promising drug for improving chronic refractory wound healing.

Trends of occupational exposure to ionizing radiation in Central China for the period 2000-2021.

A retrospective analysis of occupational exposure to ionizing radiation from medical uses and industrial uses in the three provinces of Central China from 2000 to 2021 was conducted. The average annual effective dose in medical uses and industrial uses decreased from 2.042 mSv and 2.334 mSv in 2000-2002 to 0.476 mSv and 0.371 mSv in 2021 respectively; the fraction of monitored workers receiving annual dose not exceeding 1 mSv increased from 60.78% and 74.45% in 2000-2002 to 94.20% and 96.85% in 2021 respectively, while receiving annual doses exceeding 20 mSv declined from 1.35% and 1.91% in 2000-2002 to 0.18% and 0.03% in 2021 respectively. The average annual effective dose and NR20 in the period 2000-2021 were relatively high in professional public health institutions (0.955 mSv and 0.004) and hospitals (0.815 mSv and 0.004). In 2021, the average annual effective dose to monitored workers in different occupational categories in medical uses in the three provinces of Central China were in the range of 0.199-0.692 mSv, with interventional radiology received the highest dose and NR20 (0.692 mSv and 0.005); the average annual effective dose ranged from 0.161 to 0.493 mSv in industrial uses, with industrial radiography received the highest dose and NR20 (0.493 mSv and 0.001). Occupational exposure in medical uses and industrial uses declined obviously in Central China, and the groups receiving higher doses are the radiation workers working in hospitals and professional public health institutions, or engaged in interventional radiology, nuclear medicine and industrial radiography, warranting more effective radiation protection measures.

Clinical evidence for efficacy of pembrolizumab in MSI-H and TMB-H advanced solid tumor: results from three cancer centers in China.

BACKGROUND: Pembrolizumab has been indicated in the treatment of solid tumors with high frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); however, real-world data on the effectiveness of pembrolizumab with or without chemotherapy in this molecular subset remain limited. Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H. METHODS: This retrospective study analyzed data from 116 patients with MSI-H or TMB-H advanced solid cancers who received pembrolizumab with or without chemotherapy regardless of treatment setting. We analyzed objective response rate (ORR) and progression-free survival (PFS). RESULTS: The top three cancer types were colorectal (48.6% MSI-H, 6.5% TMB-H), lung (15.4% MSI-H, 84.4% TMB-H), and gastric (15.4% MSI-H, 5.1% TMB-H). The ORR with pembrolizumab was 52.6%, including complete response (CR) observed in 8.6% (n = 10) of cases and partial responses (PR) in 43.9% (n = 51). Of the 93 patients who received first-line pembrolizumab, 52 patients achieved objective response (10 CR, 42 PR), with a median PFS of 14.0 months (95% confidence intervals [CI] 6.6-21.4). Of the 23 who received subsequent-line pembrolizumab, the ORR was 39.1%, disease control rate was 91.3%, and median PFS was 5.7 months (95% CI 3.9-7.5). Treatment-related adverse events were observed in 32 patients (27.6%), with no reported treatment-related fatal adverse events. CONCLUSION: Our study provides real-world evidence on the clinical effectiveness of pembrolizumab with or without chemotherapy in the treatment of patients with MSI-H and TMB-H advanced solid cancers.

Ultrathin Parylene C-based sensitivity-gain nanoplasmonic sensor integrated on VCSEL for Aß42 detection.

As Alzheimer's disease prevalence continues to rise, there is an increasing demand for efficient on-chip biosensors capable of early biomarker detection. This study presents a novel biosensor chip leveraging vertical cavity surface emitting laser (VCSEL) technology, with Parylene C serving as the antibody coupling layer and utilizing a streamlined one-step antibody modification method. Integration of Parylene C enhances chip sensitivity from 34.28 µW/RIU to 40.32 µW/RIU. Moreover, post-testing removal of Parylene C enables chip reusability without significant alteration of results. The sensor demonstrates effective detection of Aß42, an Alzheimer's biomarker, exhibiting a linear range of 1-200 ng/mL and a detection limit of 0.26 ng/mL. These findings underscore the reusability and reliability of the ultrathin Parylene C-based VCSEL biosensor chip, highlighting its potential for point-of-care Alzheimer's disease diagnosis.

Different evasion strategies in multiple myeloma.

Multiple myeloma is the second most common malignant hematologic malignancy which evolved different strategies for immune escape from the host immune surveillance and drug resistance, including uncontrolled proliferation of malignant plasma cells in the bone marrow, genetic mutations, or deletion of tumor antigens to escape from special targets and so. Therefore, it is a big challenge to efficiently treat multiple myeloma patients. Despite recent applications of immunomodulatory drugs (IMiDS), protease inhibitors (PI), targeted monoclonal antibodies (mAb), and even hematopoietic stem cell transplantation (HSCT), it remains hardly curable. Summarizing the possible evasion strategies can help design specific drugs for multiple myeloma treatment. This review aims to provide an integrative overview of the intrinsic and extrinsic evasion mechanisms as well as recently discovered microbiota utilized by multiple myeloma for immune evasion and drug resistance, hopefully providing a theoretical basis for the rational design of specific immunotherapies or drug combinations to prevent the uncontrolled proliferation of MM, overcome drug resistance and improve patient survival.

Response of tree growth to nutrient addition is size dependent in a subtropical forest.

Understanding how nutrient addition affects the tree growth is critical for assessing forest ecosystem function and processes, especially in the context of increased nitrogen (N) and phosphorus (P) deposition. Subtropical forests are often considered N-rich and P-poor ecosystems, but few existing studies follow the traditional "P limitation" paradigm, possibly due to differences in nutrient requirements among trees of different size classes. We conducted a three-year fertilization experiment with four treatments (Control, N-treatment, P-treatment, and NP-treatment). We measured soil nutrient availability, leaf stoichiometry, and relative growth rate (RGR) of trees across three size classes (small, medium and large) in 64 plots. We found that N and NP-treatments increased the RGR of large trees. P-treatment increased the RGR of small trees. RGR was mainly affected by N addition, the total effect of P addition was only 10 % of that of N addition. The effect of nutrient addition on RGR was mainly regulated by leaf stoichiometry. This study reveals that nutrient limitation is size dependent, indicating that continuous unbalanced N and P deposition will inhibit the growth of small trees and increase the instability of subtropical forest stand structure, but may improve the carbon sink function of large trees.

Digital twins for health: a scoping review.

The use of digital twins (DTs) has proliferated across various fields and industries, with a recent surge in the healthcare sector. The concept of digital twin for health (DT4H) holds great promise to revolutionize the entire healthcare system, including management and delivery, disease treatment and prevention, and health well-being maintenance, ultimately improving human life. The rapid growth of big data and continuous advancement in data science (DS) and artificial intelligence (AI) have the potential to significantly expedite DT research and development by providing scientific expertise, essential data, and robust cybertechnology infrastructure. Although various DT initiatives have been underway in the industry, government, and military, DT4H is still in its early stages. This paper presents an overview of the current applications of DTs in healthcare, examines consortium research centers and their limitations, and surveys the current landscape of emerging research and development opportunities in healthcare. We envision the emergence of a collaborative global effort among stakeholders to enhance healthcare and improve the quality of life for millions of individuals worldwide through pioneering research and development in the realm of DT technology.

Platelet RNA sequencing reveals profile of caffeic acid affecting hemostasis in mice.

Background: Caffeic acid (CA) is a naturally occurring phenolic compound with diverse pharmacologic properties. CA plays a crucial role in hemostasis by increasing platelet count. However, the mechanism by which CA regulates platelets to promote hemostasis remains unclear. Objectives: We aim to identify the potential target pathways and genes by which CA regulates platelets to promote hemostasis. Methods: We performed RNA sequencing (RNA-seq) analysis of mouse platelet pools in both the CA-gavaged group and phosphate-buffered saline-gavaged group. Results: The 12,934 expressed transcripts had been annotated after platelet RNA-seq. Compared with the phosphate-buffered saline group, 987 differentially expressed genes (DEGs) were identified, of which 466 were downregulated and 521 were upregulated in CA group. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome gene set enrichment analysis demonstrated that upregulated DEGs were enriched in the pathways of hemostasis, platelet activation, signaling, aggregation, and degranulation. Moreover, Kyoto Encyclopedia of Genes and Genomes and Reactome gene set enrichment analysis revealed that 5 of the 25 cosignificantly upregulated DEGs were essential in CA-mediated platelet regulation to promote hemostasis. Conclusion: Our findings of platelet RNA-seq analysis demonstrate that CA regulates the gene expression of hemostasis and platelet activation-related pathways to increase platelet count and promote hemostasis. It will also provide reference molecular resources for future research on the function and mechanism by which CA regulates platelets to promote hemostasis.

YAP1-CPNE3 positive feedback pathway promotes gastric cancer cell progression.

Hippo-Yes-associated protein 1 (YAP1) plays an important role in gastric cancer (GC) progression; however, its regulatory network remains unclear. In this study, we identified Copine III (CPNE3) was identified as a novel direct target gene regulated by the YAP1/TEADs transcription factor complex. The downregulation of CPNE3 inhibited proliferation and invasion, and increased the chemosensitivity of GC cells, whereas the overexpression of CPNE3 had the opposite biological effects. Mechanistically, CPNE3 binds to the YAP1 protein in the cytoplasm, inhibiting YAP1 ubiquitination and degradation mediated by the E3 ubiquitination ligase ß-transducin repeat-containing protein (ß-TRCP). Thereby activating the transcription of YAP1 downstream target genes, which creates a positive feedback cycle to facilitate GC progression. Immunohistochemical analysis demonstrated significant upregulation of CPNE3 in GC tissues. Survival and Cox regression analyses indicated that high CPNE3 expression was an independent prognostic marker for GC. This study elucidated the pivotal involvement of an aberrantly activated CPNE3/YAP1 positive feedback loop in the malignant progression of GC, thereby uncovering novel prognostic factors and therapeutic targets in GC.

TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer.

BACKGROUND: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. METHODS: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). RESULTS: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. CONCLUSIONS: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.

[Clinical outcomes and bone resection analysis of unilateral double-channel endoscopic technique in treating lumbar disc herniation].

OBJECTIVE: To explore clinical outcomes and bone resection of interlaminar fenestration decompression and unilateral biportal endoscopic (UBE) technique in treating lumbar disc herniation(LDH). METHODS: A retrospective study was performed on 105 patients with single-level LDH treated from December 2019 to December 2021. Fifty-four patients in UBE group,including 32 males and 22 females,aged from 18 to 50 years old with an average of(38.7±9.3) years old,were treated with UBE,29 patients with L4,5 and 25 patients with L5S1. There were 51 patients in small fenestration group,including 27 males and 24 females,aged from 18 to 50 years old with an average of (39.9±10.0) years old,were treated with small fenestration,25 patients with L4,5 and 26 patients with L5S1. Perioperative indexes,such as operation time,postoperative time of getting out of bed and hospital stay were observed and compared between two groups. Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between two groups before operation and 1,3,6 and 12 months after operation,respectively;and modified MacNab evaluation criteria was used to evaluate clinical efficacy. Amount of bone resection and retention rate of inferior articular process laminoid complex were compared between two groups. RESULTS: All 105 patients were successfully completed operation. Both of two groups were followed up from 6 to 12 months with an average of (10.69±2.49) months. Operation time,postoperative time of getting out of bed and hospital stay were (58.20±5.54) min,(2.40±0.57) d and (3.80±0.61) d in UBE group,and (62.90±7.14) min,(4.40±0.64) d and (4.40±0.64) d in small fenestrum group,respectively;and had statistically difference between two groups(P<0.05). Postoperative VAS of low back and leg pain and ODI in both groups were significantly lower than those before surgery (P<0.05). VAS of lumbar pain in UBE group (1.37±0.49) score was lower than that of small fenestration group (2.45±0.64) score,and had statistically difference (t=9.745,P<0.05). Postoperative ODI in UBE group at 1 and 3 months were (28.54±3.31) % and (22.87±3.23) %,respectively,which were lower than those in small fenestra group (36.31±9.08) % and (29.90±8.36) %,and the difference was statistically significant (P<0.05). There were no significant difference in VAS and ODI between two groups at other time points (P>0.05). According to the modified MacNab evaluation criteria at the latest follow-up,49 patients got excellent result,3 good,and 2 fair in UBE group. In small fenestration group,35 patients got excellent,12 good,and 4 fair. In UBE group,amount of bone resection on L4,5 segment was (0.45±0.08) cm3 and (0.31±0.08) cm3 on the segment of L5S1. In small fenestration group,amount of bone resection on L4,5 segment was (0.57±0.07) cm3 and (0.49±0.04) cm3 on the segment of L5S1,and amount of bone resection of lower articular process laminar complex on the same segment in UBE group was less than that in small fenestration group (P<0.05). In UBE group,retention rate of laminoid complex on L4,5 segment was (0.73±0.04) and L5S1 segment was (0.83±0.03),while L4,5 segment was(0.68±0.06) and L5S1 segment was (0.74±0.04) in small fenestration group,the lower articular process laminar complex retention rate in UBE group was higher than that in small fenestration group(P<0.05). CONCLUSION: Both unilateral double-channel endoscopy and small fenestration of laminae could achieve good clinical results in treating LDH,but UBE has advantages of less trauma,higher efficiency,faster postoperative recovery and less damage to bone structure.

Secreted salt and hydrodynamic factors combine to affect dynamic fluctuations of microplastics on mangrove leaves.

Mangrove leaves have been acknowledged as crucial sink for coastal microplastics (MPs). Whereas, the temporal dynamics of MPs intercepted by mangrove leaves have remained poorly understood. Here, we detected MPs intercepted by submerged and non-submerged mangrove leaves over time and the potential driving factors. Abundance and characteristics of MPs interception by mangrove leaves exhibited dynamic fluctuations, with the coefficient of variation (CV) of submerged mangrove leaves (CV = 0.604; 1.76 n/g to 15.45 n/g) being approximately twofold higher than non-submerged mangrove leaves (CV = 0.377; 0.74 n/g to 3.28 n/g). Partial least squares path model (PLS-PM) analysis further illustrated that MPs abundance on submerged mangrove leaves were negative correlated to hydrodynamic factors (i.e., current velocity and tidal range). Intriguingly, secreted salt as a significantly driver of MPs intercepted by mangrove leaves. Results of this work highlights that MPs intercepted by mangrove leaves is characterized by dynamic fluctuations and reveals the importance of hydrodynamic factors and secreted salt. Overall, this work identifies the pivotal buffering role played by mangrove leaves in intercepting MPs, which provides basic knowledge for better understanding of microplastic pollution status and control from mangrove plants.

Photoelectrochemical sensor based on AuNPs@WO3@TpPa-1-COF for quantification of DNA methylation levels.

A "signal-off" photoelectrochemical (PEC) sensing platform has been designed for the ultrasensitive detection of DNA methylation levels and multiple methylated sites. The platform employs tungsten trioxide and TpPa-1-COF loaded by gold nanoparticle (AuNPs@WO3@TpPa-1-COF) composite material as the photoactive component and p-type reduced graphene (rGO) as an efficient quencher. The PEC signal of AuNPs@WO3@TpPa-1-COF composite is effectively quenched in the presence of p-type rGO, because p-type rGO can compete with AuNPs@WO3@TpPa-1-COF to deplete light energy and electron donors. In addition, a hybrid strand reaction (HCR) amplification strategy fixes more target DNA and then combines with rGO-modified anti-5-methylcytosine antibody to facilitate ultrasensitive DNA methylation detection. Under optimal conditions, DNA methylation can be measured within a linear concentration range of 10-14 to 10-8 M, with an exceptionally low detection limit of 0.19 fM (S/N = 3). At the same time, the platform can conduct quantitative determination of multi-site methylation, with the linear equation △I = 44.19LogA + 61.43, and the maximum number of methylation sites is 5. The sensor demonstrates high sensitivity, excellent selectivity, and satisfactory stability. Furthermore, the proposed signal-off PEC strategy was successfully employed to detect DNA methylation in spiked human serum samples, with recoveries ranging from 93.17 to 107.28% and relative standard deviation (RSD) ranging from 1.15 to 5.49%.

Nanomaterial-Based Strategies for Preventing Tumor Metastasis by Interrupting the Metastatic Biological Processes.

Tumor metastasis is the primary cause of cancer-related deaths. The prevention of tumor metastasis has garnered notable interest and interrupting metastatic biological processes is considered a potential strategy for preventing tumor metastasis. The tumor microenvironment (TME), circulating tumor cells (CTCs), and premetastatic niche (PMN) play crucial roles in metastatic biological processes. These processes can be interrupted using nanomaterials due to their excellent physicochemical properties. However, most studies have focused on only one aspect of tumor metastasis. Here, the hypothesis that nanomaterials can be used to target metastatic biological processes and explore strategies to prevent tumor metastasis is highlighted. First, the metastatic biological processes and strategies involving nanomaterials acting on the TME, CTCs, and PMN to prevent tumor metastasis are briefly summarized. Further, the current challenges and prospects of nanomaterials in preventing tumor metastasis by interrupting metastatic biological processes are discussed. Nanomaterial-and multifunctional nanomaterial-based strategies for preventing tumor metastasis are advantageous for the long-term fight against tumor metastasis and their continued exploration will facilitate rapid progress in the prevention, diagnosis, and treatment of tumor metastasis. Novel perspectives are outlined for developing more effective strategies to prevent tumor metastasis, thereby improving the outcomes of patients with cancer.

Dipterocarpoidae genomics reveal their demography and adaptations to Asian rainforests.

Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.

USP18 Stabilized FTO Protein to Activate Mitophagy in Ischemic Stroke Through Repressing m6A Modification of SIRT6.

Ischemic stroke (IS) is a dangerous cerebrovascular disorder with a significant incidence and death rate. Ubiquitin-specific peptidase 18 (USP18) has been proven to mitigate ischemic brain damage; however, its potential regulatory mechanisms remain unclear. In vivo and in vitro models of IS were established by middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R). Neurocyte injury was detected by MTT, LDH, ROS level, mitochondrial membrane potential (Δψm), and flow cytometry. Molecular expression was evaluated by qPCR, Western blotting, and immunofluorescence staining. Molecular mechanisms were determined by Co-IP, RIP, and MeRIP. IS injury was determined by neurological behavior score and TTC staining. Mitophagy was observed by TEM. USP18 and fat mass and obesity-associated protein (FTO) expression declined after OGD/R. Dysfunctional mitochondrial and apoptosis in OGD/R-stimulated neurocytes were eliminated by USP18/FTO overexpression via mitophagy activation. USP18-mediated de-ubiquitination was responsible for increasing FTO protein stability. Up-regulation of FTO protein restrained m6A modification of sirtuin6 (SIRT6) in a YTHDF2-dependent manner to enhance SIRT6 expression and subsequent activation of AMPK/PGC-1α/AKT signaling. FTO induced mitophagy to ameliorate nerve cell damage through SIRT6/AMPK/PGC-1α/AKT pathway. Finally, USP18/FTO overexpression relieved IS in rats via triggering SIRT6/AMPK/PGC-1α/AKT axis-mediated mitophagy. USP18 increased FTO protein stability to trigger SIRT6-induced mitophagy, thus mitigating IS. Our data unravel the novel neuroprotective mechanism of USP18 and suggest its potential as a promising treatment target for IS.