A new surgical technique of robotic-assisted laparoscopic nephroureterectomy without re-docking in a single position: a single center experience.

A nephroureterectomy conventionally consists of two independent section, which will considerably prolong the operation time. We developed a novel surgical technique for robotic-assisted laparoscopic nephroureterectomy without re-docking in a single position and aimed to access the safety, feasibility, and efficiency of our novel surgical technique. From August 2021 to October 2023, 53 patients who received robotic-assisted laparoscopic nephroureterectomy were retrospectively enrolled in this study. 25 patients underwent traditional nephroureterectomy and 28 patients underwent single-position nephroureterectomy. The basic characteristics of the enroll patients, perioperative parameters, and oncological outcomes were gathered and compared between novel technique robotic surgery group and traditional surgery group. The basic characteristics between two groups had no significantly difference except for the proportion of anticoagulation therapy. The operation time in novel technique robotic surgery group was shorter than that in traditional robotic surgery group, although there was no significant difference (p = 0.403). Lymph-node dissection in novel technique robotic surgery group was obvious more common than that in traditional robotic surgery group (p = 0.037), while the incision length in novel technique robotic surgery group was obviously shorter than that in traditional robotic surgery group (p < 0.001). The oncological outcomes showed no difference between two groups. Compared with traditional robotic-assisted laparoscopic nephroureterectomy, the innovative surgical technique of robotic-assisted laparoscopic nephroureterectomy in a single position showed the advantages of less surgical time, streamlined lymph-node dissection, less trauma, and expedited postoperative recovery, which is worth promoting in clinical practice.

Highly DUV to NIR-II responsive broadband quantum dots heterojunction photodetectors by integrating quantum cutting luminescent concentrators.

Low-cost, high-performance, and uncooled broadband photodetectors (PDs) have potential applications in optical communication etc., but it still remains a huge challenge to realize deep UV (DUV) to the second near-infrared (NIR-II) detection for a single broadband PD. Herein, a single PD affording broadband spectral response from 200 to 1700 nm is achieved with a vertical configuration based on quantum dots (QDs) heterojunction and quantum cutting luminescent concentrators (QC-LC). A broadband quantum dots heterojunction as absorption layer was designed by integrating CsPbI3:Ho3+ perovskite quantum dots (PQDs) and PbS QDs to realize the spectral response from 400 to 1700 nm. The QC-LC by employing CsPbCl3:Cr3+, Ce3+, Yb3+, Er3+ PQDs as luminescent conversion layer to collect and concentrate photon energy for boosting the DUV-UV (200-400 nm) photons response of PDs by waveguide effect. Such broadband PD displays good stability, and outstanding sensitivity with the detectivity of 3.19 × 1012 Jones at 260 nm, 1.05 × 1013 Jones at 460 nm and 2.23 × 1012 Jones at 1550 nm, respectively. The findings provide a new strategy to construct broadband detector, offering more opportunities in future optoelectronic devices.

IRF1-mediated upregulation of PARP12 promotes cartilage degradation by inhibiting PINK1/Parkin dependent mitophagy through ISG15 attenuating ubiquitylation and SUMOylation of MFN1/2.

Osteoarthritis (OA) is an age-related cartilage-degenerating joint disease. Mitochondrial dysfunction has been reported to promote the development of OA. Poly (ADP-ribose) polymerase family member 12 (PARP12) is a key regulator of mitochondrial function, protein translation, and inflammation. However, the role of PARP12 in OA-based cartilage degradation and the underlying mechanisms are relatively unknown. Here, we first demonstrated that PARP12 inhibits mitophagy and promotes OA progression in human OA cartilage and a monosodium iodoacetate-induced rat OA model. Using mass spectrometry and co-immunoprecipitation assay, PARP12 was shown to interact with ISG15, upregulate mitofusin 1 and 2 (MFN1/2) ISGylation, which downregulated MFN1/2 ubiquitination and SUMOylation, thereby inhibiting PINK1/Parkin-dependent chondrocyte mitophagy and promoting cartilage degradation. Moreover, inflammatory cytokine-induced interferon regulatory factor 1 (IRF1) activation was required for the upregulation of PARP12 expression, and it directly bound to the PARP12 promoter to activate transcription. XAV-939 inhibited PARP12 expression and suppressed OA pathogenesis in vitro and in vivo. Clinically, PARP12 can be used to predict the severity of OA; thus, it represents a new target for the study of mitophagy and OA progression. In brief, the IRF1-mediated upregulation of PARP12 promoted cartilage degradation by inhibiting PINK1/Parkin-dependent mitophagy via ISG15-based attenuation of MFN1/2 ubiquitylation and SUMOylation. Our data provide new insights into the molecular mechanisms underlying PARP12-based regulation of mitophagy and can facilitate the development of therapeutic strategies for the treatment of OA.

A framework supporting green stormwater management for urban designers.

Multi-objective Urban Green Space (UGS) design is essential for optimizing limited resources amid diverse urban development challenges. This study introduces a new design support tool that overcomes the data-intensive and expert-reliant limitations faced by urban designers. The tool integrates stormwater management analysis within the Rhinoceros + Grasshopper platform, offering three key features: (1) quantifying stormwater volume in the 3D model, (2) estimating the space required for stormwater management in UGS, and (3) providing options for stormwater management facilities for UGS design. Across the five scenarios, the tool effectively demonstrated (1) the identification that dispersed UGS layouts collect more stormwater than aggregated ones with the same total area; (2) the consideration of the impact of weather changes on passive stormwater collection; and (3) the provision of recommendations on facility areas and locations to enhance collaborative urban and landscape design, better addressing stormwater management needs. This design support tool empowers urban designers to create more sustainable and resilient urban landscapes by addressing stormwater management challenges effectively in UGS design.

Association between weekend admission and in-hospital mortality for patients with ischemic heart disease upon surgery treatment.

Background: The existence and reasons for the weekend effect in patients with ischemic heart disease (IHD) were not yet fully identified. This study aimed to evaluate whether weekend admission was independently associated with in-hospital mortality and the possible mechanisms associated with the IHD patients. Methods: The study was a retrospective study, including IHD patients from 2015 to 2023. The International Classification of Diseases, tenth revision (ICD-10) codes were used to identify all admissions with a primary diagnosis of IHD. The sample was divided into weekday and weekend groups. We performed a multivariate logistic regression analysis and a mediation analysis to estimate the effect of weekend admission on hospital mortality. Results: A total of 18,906 IHD patients were included in the study, with an average age of 63.8 ± 12.7. Of these patients, 21.7% (n = 4,102) were admitted over the weekend. The in-hospital 30-days mortality rate was significantly higher among the patients admitted at weekends compared with those admitted at weekdays (2.0% vs. 1.1%). Respectively, the 30-day mortality rate of patients admitted on weekends was higher compared to patients admitted on weekdays among patients with surgical treatment (2.34% vs. 1.06%, OR = 1.75; 95% CI: 1.23-2.42) and with emergency admission (3.48% vs. 2.59%, OR = 1.56; 95% CI: 1.05-2.28). Mediation analyses showed that the surgical scheduling had significant mediated effects on the associations of admission time with mortality risk. Conclusions: IHD patients with a surgical therapy or admitted from emergency department had a significantly higher risk of mortality when admitted on weekends compared to weekdays. These findings have potential implications for resource allocation and redistribution of surgery to weekends in hospitals.

Surface settlement induced by frictional force of epb shield tunneling in sandy gravels.

The excavation of Earth Pressure Balance (EPB) shield can be divided into two distinct stages, i.e. advancing and lining installation. The frictional force applied on surrounding soils reverses at these two stages, which is harmful to the settlement control. Based on Mindlin's method, a new model of surface settlement is derived to involve the reversed friction. A closed form formula is then obtained for the major type of metro tunnels. Main operational parameters are also used as input of the formula. Numerous operational data and measured settlements are collected from EPB tunnels of Chengdu Metro, Line 7. The proposed formula is validated against these field data in sandy gravels. It is shown that the new formula gives reasonable prediction of surface settlement along the tunnel sections. The accuracy of new formula is significantly higher than that of Peck's formula. This study provides a new vision in settlement control of EPB shield tunneling. The increase of chamber pressure will induce higher negative friction during the lining installation. Therefore, surface settlement of EPB tunneling cannot be controlled by just increasing chamber pressure. A balanced relationship between the chamber pressure and the thrust should be maintained instead.

LncRNA HOXA11-AS intercepts the POU2F2-mediated downregulation of SLC3A2 in osteoarthritis to suppress ferroptosis.

BACKGROUND: Osteoarthritis (OA) is a prevalent ailment characterized by the gradual degradation of joints, resulting in discomfort and restricted movement. The recently proposed mechanism of ferroptosis is intricately associated with the initiation and progression of OA. Our study found that the long non-coding RNA HOXA11-AS reduces ferroptosis by increasing the expression of SLC3A2 through the transcription factor POU2F2. MATERIALS AND METHODS: HOXA11-AS was identified through lncRNA microarray analysis, and its impact on chondrocytes and extracellular matrix was assessed using real-time quantitative PCR, western blotting, and CCK8 assays. Subsequently, overexpression of HOXA11-AS in the knee joints of mice confirmed its protective efficacy on chondrocyte phenotype in the OA model. The involvement of HOXA11-AS in regulating ferroptosis via SLC3A2 was further validated through RNA sequencing analysis of mouse cartilage and the assessment of malondialdehyde levels and glutathione peroxidase activity. Finally, a combination of RNA sequencing, pull-down assays, mass spectrometry (MS), and chromatin immunoprecipitation (ChIP) techniques was employed to identify POU2F2 as the crucial transcription factor responsible for repressing the expression of SLC3A2, which can be effectively inhibited by HOXA11-AS. RESULTS: Our study demonstrated that HOXA11-AS effectively enhanced the metabolic homeostasis of chondrocytes, and alleviated the progression of OA in vitro and in vivo experiments. Furthermore, HOXA11-AS was found to enhance SLC3A2 expression, a key regulator of ferroptosis, by interacting with the transcriptional repressor POU2F2. CONCLUSIONS: HOXA11-AS promotes SLC3A2 expression and inhibits chondrocyte ferroptosis, by binding to the transcriptional repressor POU2F2, offering a promising and innovative therapeutic approach for OA.

Printing of 3D photonic crystals in titania with complete bandgap across the visible spectrum.

A photonic bandgap is a range of wavelengths wherein light is forbidden from entering a photonic crystal, similar to the electronic bandgap in semiconductors. Fabricating photonic crystals with a complete photonic bandgap in the visible spectrum presents at least two important challenges: achieving a material refractive index > ~2 and a three-dimensional patterning resolution better than ~280 nm (lattice constant of 400 nm). Here we show an approach to overcome such limitations using additive manufacturing, thus realizing high-quality, high-refractive index photonic crystals with size-tunable bandgaps across the visible spectrum. We develop a titanium ion-doped resin (Ti-Nano) for high-resolution printing by two-photon polymerization lithography. After printing, the structures are heat-treated in air to induce lattice shrinkage and produce titania nanostructures. We attain three-dimensional photonic crystals with patterning resolution as high as 180 nm and refractive index of 2.4-2.6. Optical characterization reveals ~100% reflectance within the photonic crystal bandgap in the visible range. Finally, we show capabilities in defining local defects and demonstrate proof-of-principle applications in spectrally selective perfect reflectors and chiral light discriminators.

Bioaccumulation of Atmospherically Deposited Cadmium in Soybean: Three-Year Field Experiment Combined with Cadmium Isotopes.

Atmospheric deposition plays a significant role in introducing cadmium (Cd) into agroecological systems; however, accurately determining its accumulation in crops through foliar and root uptake presents challenges. This study investigated the bioaccumulation of atmospherically deposited Cd in soybean using a three-year fully factorial atmospheric exposure experiment incorporating Cd isotope analysis. Results shown that atmospheric deposition accounted for 1-13% of soil Cd pools, yet contributed 11-72% of Cd to soybean tissues during the growing seasons. Over the course of soil exposure to atmospheric deposition ranging from 1 to 3 years, no notable variations were observed in Cd concentrations in soil solutions and soybean tissues, nor in isotope ratios. Newly deposited Cd was a major source in soybean plants, and the bioavailability of deposited Cd rapidly aged in soils. Atmospheric Cd enriched in lighter isotopes induced negative isotope shifts in soybean plants. By employing an optimized isotope mixing model in conjunction with a mass balance approach, foliar Cd uptake contributed 13-51%, 16-45%, and 21-56% to stem, leaf, and seed, respectively. This study highlights substantial contribution of foliar uptake of atmospheric deposition to Cd levels in soybean and controlling foliar uptake as a potential strategy in agroecological systems experiencing high atmospheric Cd deposition.

Efficacy and Safety of Biosimilar SCT510 Compared with Bevacizumab for the First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study.

INTRODUCTION: SCT510 is a biosimilar to bevacizumab (Avastin) reference product (RP) that is approved for various metastatic cancers. In this study, we aimed to demonstrate the equivalence of SCT510 and bevacizumab in terms of efficacy, safety, immunogenicity and pharmacokinetics (PK) in patients with advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: Patients with non-squamous NSCLC were randomized equally to the SCT510 group (comprising SCT510, paclitaxel, and carboplatin) and the bevacizumab group (comprising bevacizumab, paclitaxel, and carboplatin) for 4-6 cycles, followed by maintenance monotherapy with SCT510. The primary endpoint was the objective response rate (ORR) at week 12. Secondary endpoints included 18-week ORR, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and 1-year survival rate, as well as assessments of safety, immunogenicity, and multi-dose PK analysis. RESULTS: Between March 29, 2019, and April 27, 2021, 989 patients were screened and 567 eligible patients were randomly assigned to the SCT510 group (285 patients) and the bevacizumab group (282 patients). The ORR at week 12 was 52.6% [95% confidence interval (CI) 46.66-58.55%] in the SCT510 group and 52.5% (95% CI 46.47-58.47%) in the bevacizumab group. The ORR at week 18 was 55.4% (95% CI 49.46-61.30%) for SCT510 and 55.7% (95% CI 49.68-61.62%) for bevacizumab. The ORR risk ratio (RR) at weeks 12 and 18 was 0.99 (90% CI 0.873-1.133) and 0.99 (90% CI 0.872-1.114), respectively, both within the pre-specified equivalence margin of 0.75-1.33. There were no differences between the two groups in relation to other secondary endpoints, specifically DCR, DOR, PFS, OS, and 1-year survival rate. The overall safety findings were similar between the two treatment groups, and both SCT510 and bevacizumab RP exhibited low immunogenicity. CONCLUSIONS: SCT510 is similar to bevacizumab in clinical efficacy, safety, immunogenicity, and PK in patients with advanced non-squamous NSCLC. The totality of the evidence supports the clinical equivalence of SCT510 and bevacizumab. TRIAL REGISTRATION: NCT03792074.

Methoxycarbonylation of diisobutylene into methyl isononanoate catalyzed by cobalt complexes dispersed by poly(ionic liquids).

The catalytic performance of cobalt complex catalysts coordinated with various poly(ionic liquids) for the methoxycarbonylation of diisobutene into methyl isononanoate was investigated. The poly(ionic liquids) were synthesized via a solvothermal polymerization method and were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption and elemental analyses. A diisobutene conversion of 88.0% and a methyl isononanoate selectivity of 91.4% were achieved using HVIMI-VPy-DVB (1 : 1)@Co2(CO)8 as catalysts at the optimized reaction conditions of 8.0 MPa CO and 150 °C. Furthermore, the catalyst system can be suitable for the methoxycarbonylation of various terminal olefins and exhibits high recoverability and thermostability.

Study on the Aging Precipitation Behavior and Kinetics of Al-10.0Zn-3.0Mg-2.8Cu Alloy by Pre-Deformation Treatment.

In this paper, the effect of thermomechanical treatment process on the hardening behavior, grain microstructure, precipitated phase, and tensile mechanical properties of the new high-strength and high-ductility Al-10.0Zn-3.0Mg-2.8Cu alloy was studied, and the optimal thermomechanical treatment process was established. The strengthening and toughening mechanisms were revealed, which provided technical and theoretical guidance for the engineering application of this kind of high strength-ductility aluminum alloy. Al-10.0Zn-3.0Mg-2.8Cu alloy cylindrical parts with external longitudinal reinforcement were prepared by a composite extrusion deformation process (reciprocal upsetting + counter-extrusion) with a true strain up to 2.56, and the organizational evolution of the alloys during the extrusion deformation process and the influence of pre-stretching treatments on the subsequent aging precipitation behaviors and mechanical properties were investigated. The results show that firstly, the large plastic deformation promotes the fragmentation of coarse insoluble phases and the occurrence of dynamic recrystallization, which results in the elongation of the grains along the extrusion direction, and the volume fraction of recrystallization reaches 42.4%. Secondly, the kinetic study showed that the decrease in the activation energy of precipitation increased the nucleation sites, which further promoted the diffuse distribution of the second phase in the alloy and a higher number of nucleation sites, while limiting the coarsening of the precipitated phase. When the amount of pre-deformation was increased from 0% to 2%, the size of the matrix precipitated phase decreased from 5.11 µm to 4.1 µm, and when the amount of pre-deformation was increased from 2% to 7%, the coarsening of the matrix precipitated phase took place, and the size of the phase increased from 4.1 µm to 7.24 µm. The finalized heat treatment process for the deformation of the aluminum alloy tailframe was as follows: solution (475 °C/3 h) + 2% pre-stretching + aging (120 °C/24 h), at which the comprehensive performance of the alloy was optimized, with a tensile strength of 634.2 MPa, a yield strength of 571.0 MPa, and an elongation of 15.2%. The alloy was strengthened by both precipitation strengthening and dislocation strengthening. After 2% pre-stretching, the fracture surface starts to be dominated by dense tough nest structure, and most of them are small tough nests, and small and dense tough nests are the main reason for the increase in alloy toughness after 2% pre-stretching deformation.

Molecular composition limits the reaction kinetics of riverine dissolved organic matter decomposition.

The bioavailability and degradation of riverine dissolved organic matter (DOM) play crucial roles in greenhouse gas emissions; however, studies on the kinetic decomposition of fluvial DOM remain scarce. In this study, the decomposition kinetics of dissolved organic carbon (DOC) were characterized using the reactivity continuum model through 28-day bio-incubation experiments with water samples from the Yangtze River. The relationship between DOM composition and decomposition kinetics was analyzed using optical and molecular characterization combined with apparent decay coefficients. Our results revealed that DOM compounds rich in nitrogen and sulfur were predominantly removed, exhibiting a transition from an unsaturated to a saturated state following microbial degradation. These heteroatomic compounds, which constituted 75.61 % of the DOM compounds positively correlated with the decay coefficient k0, underwent preferential degradation in the early stages of bio-incubation due to their higher bioavailability. Additionally, we observed that S-containing fractions with high molecular weight values (MW > 400 Da) may be associated with larger reactivity grades. This study underscored the complex interplay between DOM composition and its kinetic decomposition in river ecosystems, providing further support for the significance of molecular composition in large river DOM as crucial factors affecting decomposition.

CaCO3-Encapsulated polydopamine with an adsorbed TLR7 agonist for improved tumor photothermal immunotherapy.

Because of the tumor's recurrence and significant metastasis, the standard single-therapy paradigm has failed to meet clinical requirements. Recently, researchers have focused their emphasis on phototherapy and immunogenic cell death (ICD) techniques. In response to the current problems of immunotherapy, a multifunctional drug delivery nanosystem (PDA-IMQ@CaCO3-blinatumomab, PICB) was constructed by using high physiological compatibility of polydopamine (PDA) and calcium carbonate (CaCO3). Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ) and bispecific antibody (BsAb) blinatumomab were loaded onto PDA-CaCO3 nanoparticles (NPs). The findings revealed that the system exhibited the advantages of good dispersion, high stability, excellent physiological compatibility, low toxicity, and high drug loading rate. Compared to the control group, it resulted in a 2.4-fold decrease in FOXP3+ regulatory T-cells within the tumor and a 5.0-fold increase in CD4+ effector T-cells, and promoted the production of damage-related molecular patterns to reinvigorate the ICD effect. PICB had a strong inhibitory effect on tumor growth in 4T1 tumor-bearing mice, and has no toxicity to other organs. Therefore, the multifunctional drug delivery nanosystem constructed in this study could effectively exert the properties of various components in vivo, fully demonstrate the synergistic effect between immunotherapy and photothermal therapy, thus significantly improving the tumor therapeutic efficacy, and has a promising clinical application.

Photocatalytic Synthesis of Ammonia from Hollow Coral-Like Graphitic Carbon Nitride/FeOCl Loaded with Fe-1T MoS2 Nanosheets as Cocatalysts.

Photocatalytic ammonia synthesis (PAS) represents an emerging environmentally friendly approach to ammonia production. In this work, we employed Fe doping to modify the cocatalyst 1T MoS2, enhancing the active N2 sites on Fe-1T MoS2 by inducing defects on the surface of 1T MoS2. Afterward, Fe-1T MoS2 was loaded onto a hollow coral-like graphitic carbon nitride (CCN)/FeOCl composite. Under simulated sunlight, the efficiency of 5% Fe-1T MoS2@CCN/FeOCl (Fe-MCN/FeOCl) reached 367.62 µmol g-1 h-1, surpassing 1T MoS2@CCN(MCN) by 3.2 times, CCN by 16.9 times, and g-C3N4 by 32.5 times, where 5% means the doping amount of Fe in 1T MoS2. The good performance of Fe MCN/FeOCl should be attributed to the Fe doping in Fe-MCN/FeOCl which not only increases the separation efficiency of active sites and charge carriers, but also reduces the sample impedance significantly through the heterojunction formed between CCN and FeOCl. This work also presents a method for creating more efficient and stable photocatalysts for ammonia synthesis.

Smart roofs featuring predictive control: An upgrade for mitigating precipitation extreme-induced pluvial floods.

In the face of escalating urban pluvial floods exacerbated by climate change, conventional roof systems fall short of effectively managing precipitation extremes. This paper introduces a smart predictive solution: the Smart Internal Drainage Roof (SIDR) system, which leverages forecasted data to enhance the mitigation of pluvial floods in Central Business District (CBD) areas. Unlike traditional approaches, SIDRs utilize a synergistic combination of Rule-based Control (RBC) and Model Predictive Control (MPC) algorithms, tailored to optimize the operational efficiency of both grey and green roofs. Within the examined 1.3 km2 area in Beijing, China, SIDRs, covering 11% of the site, decreased total flooded areas by 30%-50% and eliminated 60%-100% of high-risk zones during three actual events. Moreover, SIDRs streamlined outflow processes without extending discharge time and reduced flood duration at a high-risk underpass by more than half. The SIDR's distinct features, including a high control resolution of 5 min, integration with existing waterproofs, and advanced 2D dynamic runoff visualization, position it as a scalable and cost-efficient upgrade in urban flood resilience strategies.

Multi-Step and Switchable Energy Transfer in Photoluminescent Organosilicone Capsules.

Light-harvesting is of vital importance for many events, such as photosynthesis. To efficiently gather and transfer solar energy, delicate antenna is needed, which has been achieved by algae and plants. However, construction of efficient light-harvesting systems using multiple, artificial building blocks is still challenging. Here, blue-emitting organosilicone capsules containing carbon dots (denoted as CDs-Si) in ethanol are prepared, which can effectively transfer energy to green-emitting (silicone-functionalized bodipy, Si-BODIPY) or red-emitting (rhodamine b, RhB) dyes. In ternary system, sequential Förster resonance energy transfer from CDs-Si to Si-BODIPY and further to RhB is realized, which is accompanied with a less pronounced, parallel FRET directly from CDs-Si to RhB. The overall efficiency of energy transfer reaches ≈86%. By introducing a photoswitch (1,2-bis(2,4-dimethyl-5-phenyl-3-thienyl)-3,3,4,4,5,5-hexafluoro-1-cyclopentene, DAE) to the system, the emission becomes switchable under alternative illumination with UV and visible light, leading to the formation of smart artificial light-harvesting systems.

Emergence of decadal linkage between Western Australian coast and Western-central tropical Pacific.

The impact of interbasin linkage on the weather/climate and ecosystems is significantly broader and profounder than that of only appearing in an individual basin. Here, we reveal that a decadal linkage of sea surface temperature (SST) has emerged between western Australian coast and western-central tropical Pacific since 1985, associated with continuous intensification of decadal variabilities (8-16 years). The rapid SST changes in both tropical Indian Ocean and Indo-Pacific warm pool in association to greenhouse gases and volcanoes are emerging factors resulting in enhanced decadal co-variabilities between these two regions since 1985. These SST changes induce enhanced convection variability over the Maritime Continent, leading to stronger easterlies in the western-central tropical Pacific during the warm phase off western Australian coast. The above changes bring about cooling in the western-central tropical Pacific and strengthened Leeuwin Current and anomalous cyclonic wind off western Australian coast, and ultimately resulting in enhanced coupling between these two regions. Our results suggest that enhanced decadal interbasin connections can offer further understanding of decadal changes under future warmer conditions.

RAD51 Expression as a Biomarker to Predict Efficacy of Platinum-Based Chemotherapy and PD-L1 Blockade for Muscle-Invasive Bladder Cancer.

RAD51, a key recombinase that catalyzes homologous recombination (HR), is commonly overexpressed in multiple cancers. It is curial for DNA damage repair (DDR) to maintain genomic integrity which could further determine the therapeutic response. Herein, we attempt to explore the clinical value of RAD51 in therapeutic guidance in muscle-invasive bladder cancer (MIBC). In this retrospective study, a total of 823 patients with MIBC were included. Zhongshan hospital (ZSHS) cohort (n=134) and The Cancer Genome Atlas-Bladder Cancer (TCGA-BLCA) cohort (n=391) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n=298) was utilized to interrogate the predictive efficacy of RAD51 status to programmed cell death ligand-1 (PD-L1) blockade. In addition, the association of RAD51 with genomic instability and tumor immune contexture was investigated. Patients with RAD51 overexpression were more likely to benefit from both platinum-based chemotherapy and immunotherapy rather than RAD51-low patients. The TMB high PD-L1 high RAD51 high subgroup possessed the best clinical benefits from PD-L1 blockade. RAD51-high tumors featured by genomic instability were correlated to highly inflamed and immunogenic contexture with activated immunotherapeutic pathway in MIBC. RAD51 could serve as a prognosticator for treatment response to platinum-based chemotherapy and PD-L1 inhibitor in MIBC patients. Besides, it could also improve the predictive efficacy of TMB and PD-L1.

Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress.

BACKGROUND: Cell division cyclin 25C (CDC25C) is a protein that plays a critical role in the cell cycle, specifically in the transition from the G2 phase to the M phase. Recent research has shown that CDC25C could be a potential therapeutic target for cancers, particularly for hepatocellular carcinoma (HCC). However, the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood. AIM: To explore the impact of CDC25C on cell proliferation and apoptosis, as well as its regulatory mechanisms in HCC development. METHODS: Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences (LV-CDC25C shRNA) to knock down CDC25C. Subsequently, a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo. Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays, respectively. The expression of endoplasmic reticulum (ER) stress-related molecules (glucose-regulated protein 78, X-box binding protein-1, and C/EBP homologous protein) was measured in both cells and subcutaneous xenografts using quantitative real-time PCR (qRT-PCR) and western blotting. Additionally, apoptosis was investigated using flow cytometry, qRT-PCR, and western blotting. RESULTS: CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction. A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice. CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response, ultimately promoting ER stress-induced apoptosis in HCC cells. CONCLUSION: The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.