Ablation of intestinal epithelial sialylation predisposes to acute and chronic intestinal inflammation in mice.

BACKGROUND & AIMS: Addition of sialic acids (sialylation) to glycoconjugates is a common capping step of glycosylation. Our study aims to determine the roles of the overall sialylation in intestinal mucosal homeostasis. METHODS: Mice with constitutive deletion of intestinal epithelial sialylation (IEC Slc35a1-/- mice) and mice with inducible deletion of sialylation in intestinal epithelium (TM-IEC Slc35a1-/- mice) were generated, which were used to determine the roles of overall sialylation in intestinal mucosal homeostasis by ex vivo and muti-omics studies. RESULTS: IEC Slc35a1-/- mice developed mild spontaneous microbiota-dependent colitis. Additionally, 30% of IEC Slc35a1-/- mice had spontaneous tumors in the rectum over the age of 12 months. TM-IEC Slc35a1-/- mice were highly susceptible to acute inflammation induced by 1% DSS vs controls. Loss of total sialylation was associated with reduced mucus thickness on fecal sections and within colon tissues. TM-IEC Slc35a1-/- mice showed altered microbiota with an increase in Clostridia disporicum, which is associated a global reduction in the abundance of at least 20 unique taxa; however, metabolomic analysis did not show any significant differences in short-chain fatty acid levels. Treatment with 5-fluorouracil (5-FU) led to more severe small intestine mucositis in the IEC Slc35a1-/- mice vs. WT littermates, which was associated with reduced Lgr5+ cell representation in small intestinal crypts in IEC Slc35a1-/-;Lgr5-GFP mice. CONCLUSIONS: Loss of overall sialylation impairs mucus stability and the stem cell niche leading to microbiota-dependent spontaneous colitis and tumorigenesis.

Fluorinated Naphthalene Diimides as Buried Electron Transport Materials Achieve Over 23% Efficient Perovskite Solar Cells.

Naphthalene diimides (NDI) are widely serving as the skeleton to construct electron transport materials (ETMs) for optoelectronic devices. However, most of the reported NDI-based ETMs suffer from poor interfaces with the perovskite which deteriorates the carrier extraction and device stability. Here, a representative design concept for editing the peripheral groups of NDI molecules to achieve multifunctional properties is introduced. The resulting molecule 2,7-bis(2,2,3,3,4,4,4-heptafluorobutyl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (NDI-C4F) incorporated with hydrophobic fluorine units contributes to the prevention of excessive molecular aggregation, the improvement of surface wettability and the formation of strong chemical coordination with perovskite precursors. All these features favor retarding the perovskite crystallization and achieving superior buried interfaces, which subsequently promote charge collection and improve the structural compatibility between perovskite and ETMs. The corresponding PSCs based on low-temperature processed NDI-C4F yield a record efficiency of 23.21%, which is the highest reported value for organic ETMs in n-i-p PSCs. More encouragingly, the unencapsulated devices with NDI-C4F demonstrate extraordinary stability by retaining over 90% of their initial PCEs after 2600 h in air. This work provides an alternative molecular strategy to engineer the buried interfaces and can trigger further development of organic ETMs toward reliable PSCs.

Shape-position perceptive fusion electronic skin with autonomous learning for gesture interaction.

Wearable devices, such as data gloves and electronic skins, can perceive human instructions, behaviors and even emotions by tracking a hand's motion, with the help of knowledge learning. The shape or position single-mode sensor in such devices often lacks comprehensive information to perceive interactive gestures. Meanwhile, the limited computing power of wearable applications restricts the multimode fusion of different sensing data and the deployment of deep learning networks. We propose a perceptive fusion electronic skin (PFES) with a bioinspired hierarchical structure that utilizes the magnetization state of a magnetostrictive alloy film to be sensitive to external strain or magnetic field. Installed at the joints of a hand, the PFES realizes perception of curvature (joint shape) and magnetism (joint position) information by mapping corresponding signals to the two-directional continuous distribution such that the two edges represent the contributions of curvature radius and magnetic field, respectively. By autonomously selecting knowledge closer to the user's hand movement characteristics, the reinforced knowledge distillation method is developed to learn and compress a teacher model for rapid deployment on wearable devices. The PFES integrating the autonomous learning algorithm can fuse curvature-magnetism dual information, ultimately achieving human machine interaction with gesture recognition and haptic feedback for cross-space perception and manipulation.

Erianin induces ferroptosis in GSCs via REST/LRSAM1 mediated SLC40A1 ubiquitination to overcome TMZ resistance.

In recent studies, erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, has exhibited notable anticancer properties. Ferroptosis, a novel form of programmed cell death, holds potential as a strategy to overcome Temozolomide (TMZ) resistance in glioma by inducing ferroptosis in TMZ-resistant glioma cells. Here, utilizing various phenotyping experiments, including cell counting kit-8 (CCK-8) assays, EdU assays, transwell assays, neurosphere formation assays and extreme limiting dilution (ELDA) assays, we demonstrated that erianin exerts its anticancer activity on both TMZ sensitive and TMZ-resistant glioma stem cells (GSCs). Furthermore, we made an exciting discovery that erianin enhances TMZ sensitivity in TMZ-resistant GSCs. Subsequently, we demonstrated that erianin induced ferroptosis in TMZ-resistant GSCs and enhances TMZ sensitivity through inducing ferroptosis, which was confirmed by intracellular measurements of ROS, GSH, and MDA, as well as through the use of BODIPY (581/591) C11 and transmission electron microscopy. Conversely, the ferroptosis inhibitor ferrostatin-1 (Fer-1) blocked the effects of erianin. The underlying mechanism of ferroptosis induced by erianin was further explored through co-immunoprecipitation (Co-IP) assays, ubiquitination assays, protein stability assessments, chromatin immunoprecipitation (ChIP) assays and luciferase reporter gene assays. We found that erianin specifically targets REST, inhibiting its transcriptional repression function without altering its expression levels. Consequently, this suppression of REST's role leads to an upregulation of LRSAM1 expression. In turn, LRSAM1 ubiquitinates and degrades SLC40A1, a protein that inhibits ferroptosis by exporting ferrous ions. By downregulating SLC40A1, erianin ultimately induces ferroptosis in TMZ-resistant GSCs. Taken together, our research demonstrates that the natural product erianin inhibits the malignant phenotype of GSCs and increases the sensitivity of TMZ in TMZ-resistant GSCs by inducing ferroptosis. These findings suggest erianin as a prospective compound for the treatment of TMZ-resistant glioma.

Drag reduction and degradation by sodium alginate in turbulent flow.

The utilization of drag-reducing polymers has long been hindered by their irritancy, corrosiveness, and toxicity across various domains. In this investigation, we explored sodium alginate, a natural drag reducer, for its efficacy in reducing drag and its resilience to shear in millimeter-scale pipelines. Initially, an experimental setup was devised to assess the drag reduction capabilities of sodium alginate at varying concentrations and flow rates using Response Surface Methodology (RSM). The relationship between drag reduction (DR), concentration (C), and flow rate (Q) was established by analyzing the experimental data. Subsequently, variance analysis was employed to validate the data accuracy, with a comparison between predicted and experimental DR values revealing an error margin within ± 20%. Analysis of cyclic shear testing of sodium alginate solution in tubes demonstrated its effectiveness as a shear flow drag reducer. Furthermore, results from laser particle size analysis indicated minimal molecular breakage of sodium alginate during cyclic shear.

Synergism in Binary Nanocrystals Enables Top-Illuminated HgTe Colloidal Quantum Dot Short-Wave Infrared Imager.

Thanks to their tunable infrared absorption, solution processability, and low fabrication costs, HgTe colloidal quantum dots (CQDs) are promising for optoelectronic devices. Despite advancements in device design, their potential for imaging applications remains underexplored. For integration with Si-based readout integrated circuits (ROICs), top illumination is necessary for simultaneous light absorption and signal acquisition. However, most high-performing traditional HgTe CQD photodiodes are p-on-n stack and bottom-illuminated. Herein, we report top-illuminated inverted n-on-p HgTe CQD photodiodes using a robust p-type CQD layer and a thermally evaporated Bi2S3 electron transport layer. The p-type CQD solid is achieved by exploring the synergism in binary HgTe and Ag2Te CQDs. These photodetectors show a room-temperature detectivity of 3.4 × 1011 jones and an EQE of ∼44% at ∼1.7 µm wavelength, comparable to the p-on-n HgTe CQD photodiodes. A top-illuminated HgTe CQD short-wave infrared imager (640 × 512 pixels) was fabricated, demonstrating successful infrared imaging.

Design of Co-Cured Multi-Component Thermosets with Enhanced Heat Resistance, Toughness, and Processability via a Machine Learning Approach.

Designing heat-resistant thermosets with excellent comprehensive performance has been a long-standing challenge. Co-curing of various high-performance thermosets is an effective strategy, however, the traditional trial-and-error experiments have long research cycles for discovering new materials. Herein, a two-step machine learning (ML) assisted approach is proposed to design heat-resistant co-cured resins composed of polyimide (PI) and silicon-containing arylacetylene (PSA), that is, poly(silicon-alkyne imide) (PSI). First, two ML prediction models are established to evaluate the processability of PIs and their compatibility with PSA. Then, another two ML models are developed to predict the thermal decomposition temperature and flexural strength of the co-cured PSI resins. The optimal molecular structures and compositions of PSI resins are high-throughput screened. The screened PSI resins are experimentally verified to exhibit enhanced heat resistance, toughness, and processability. The research framework established in this work can be generalized to the rational design of other advanced multi-component polymeric materials.

In situ Blending For Co-Deposition of Electron Transport and Perovskite Layers Enables Over 24% Efficiency Stable Inverted Solar Cells.

Simplifying the manufacturing processes of multilayered high-performance perovskite solar cells (PSCs) is yet of vital importance for their cost-effective production. Herein, an in situ blending strategy is presented for co-deposition of electron transport layer (ETL) and perovskite absorber by incorporating (3-(7-butyl-1,3,6,8-tetraoxo-3,6,7,8-tetrahydrobenzo- [lmn][3,8]phenanthrolin-2(1H)-yl)propyl)phosphonic acid (NDP) into the perovskite precursor solutions. The phosphonic acid-like anchoring group coupled with its large molecular size drives the migration of NDP toward indium tin oxide (ITO) surface to form a distinct ETL during perovskite film forming. This strategy circumvents the critical wetting issue and simultaneously improves the interfacial charge collection efficiencies. Consequently, n-i-p PSCs based on in situ blended NDP achieve a champion power conversion efficiency (PCE) of 24.01%, which is one of the highest values for PSCs using organic ETLs. This performance is notably higher than that of ETL-free (21.19%) and independently spin-coated (21.42%) counterparts. More encouragingly, the in situ blending strategy dramatically enhances the device stability under harsh conditions by retaining over 90% of initial efficiencies after 250 h in 100 °C or 65% humidity storage. Moreover, this strategy is universally adaptable to various perovskite compositions, device architectures, and electron transport materials (ETMs), showing great potential for applications in diverse optoelectronic devices.

EDTP enhances and protects the fluorescent signal of GFP in cleared and expanded tissues.

Advanced 3D high-resolution imaging techniques are essential for investigating biological challenges, such as neural circuit analysis and tumor microenvironment in intact tissues. However, the fluorescence signal emitted by endogenous fluorescent proteins in cleared or expanded biological samples gradually diminishes with repeated irradiation and prolonged imaging, compromising its ability to accurately depict the underlying scientific problem. We have developed a strategy to preserve fluorescence in cleared and expanded tissue samples during prolonged high-resolution three-dimensional imaging. We evaluated various compounds at different concentrations to determine their ability to enhance fluorescence intensity and resistance to photobleaching while maintaining the structural integrity of the tissue. Specifically, we investigated the impact of EDTP utilization on GFP, as it has been observed to significantly improve fluorescence intensity, resistance to photobleaching, and maintain fluorescence during extended room temperature storage. This breakthrough will facilitate extended hydrophilic and hydrogel-based clearing and expansion methods for achieving long-term high-resolution 3D imaging of cleared biological tissues by effectively safeguarding fluorescent proteins within the tissue.

Archimedean Spirals with Controllable Chirality: Disk Substrate-Mediated Solution Assembly of Rod-Coil Block Copolymers.

Spirals are common in nature; however, they are rarely observed in polymer self-assembly systems, and the formation mechanism is not well understood. Herein, we report the formation of two-dimensional (2D) spiral patterns via microdisk substrate-mediated solution self-assembly of polypeptide-based rod-coil block copolymers. The spiral pattern consists of multiple strands assembled from the block copolymers, and two central points are observed. The spirals fit well with the Archimedean spiral model, and their chirality is dependent on the chirality of the polypeptide blocks. As revealed by a combination of experiments and theoretical simulations, these spirals are induced by an interplay of the parallel ordering tendency of the strands and circular confinement of the microdisks. This work presents the first example regarding substrate-mediated self-assembly of block copolymers into spirals. The gained information could not only enhance our understanding of natural spirals but also assist in both the controllable preparations and applications of spiral nanostructures.

Advances in Hydrogels of Drug Delivery Systems for the Local Treatment of Brain Tumors.

The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood-brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at the histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach to addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

Deletion of Talin1 in Myeloid Cells Facilitates Atherosclerosis in Mice.

BACKGROUND: Integrin-regulated monocyte recruitment and cellular responses of monocyte-derived macrophages are critical for the pathogenesis of atherosclerosis. In the canonical model, talin1 controls ligand binding to integrins, a prerequisite for integrins to mediate leukocyte recruitment and induce immune responses. However, the role of talin1 in the development of atherosclerosis has not been studied. Our study investigated how talin1 in myeloid cells regulates the progression of atherosclerosis. METHODS: On an Apoe-/- background, myeloid talin1-deficient mice and the control mice were fed with a high-fat diet for 8 or 12 weeks to induce atherosclerosis. The atherosclerosis development in the aorta and monocyte recruitment into atherosclerotic lesions were analyzed. RESULTS: Myeloid talin1 deletion facilitated the formation of atherosclerotic lesions and macrophage deposition in lesions. Talin1 deletion abolished integrin ß2-mediated adhesion of monocytes but did not impair integrin α4ß1-dependent cell adhesion in a flow adhesion assay. Strikingly, talin1 deletion did not prevent Mn2+- or chemokine-induced activation of integrin α4ß1 to the high-affinity state for ligands. In an in vivo competitive homing assay, monocyte infiltration into inflamed tissues was prohibited by antibodies to integrin α4ß1 but was not affected by talin1 deletion or antibodies to integrin ß2. Furthermore, quantitative polymerase chain reaction and ELISA analysis showed that macrophages produced cytokines to promote inflammation and the proliferation of smooth muscle cells. Ligand binding to integrin ß3 inhibited cytokine generation in macrophages, although talin1 deletion abolished the negative effects of integrin ß3. CONCLUSIONS: Integrin α4ß1 controls monocyte recruitment during atherosclerosis. Talin1 is dispensable for integrin α4ß1 activation to the high-affinity state and integrin α4ß1-mediated monocyte recruitment. Yet, talin1 is required for integrin ß3 to inhibit the production of inflammatory cytokines in macrophages. Thus, intact monocyte recruitment and elevated inflammatory responses cause enhanced atherosclerosis in talin1-deficient mice. Our study provides novel insights into the roles of myeloid talin1 and integrins in the progression of atherosclerosis.

Split ring hole metamaterial-enhanced pyroelectric detector for efficient multi-narrowband terahertz detection.

Derived from infrared pyroelectric detection, typical terahertz (THz) pyroelectric detectors have low sensitivity at low-frequency THz bands. Based on the high-efficiency absorption of the metamaterial perfect absorber (MPA), a novel split ring hole metamaterial-enhanced pyroelectric detector is proposed to achieve efficient multi-narrowband THz detection. Using high frequency simulation software (HFSS), the dimensional parameters including ring radius, ring width, connection beam width, array period, and thickness, are optimized to enhance efficient multi-narrowband absorption. The as-optimized metamaterial-enhanced detectors are fabricated via micro-nano manufacturing technology. The voltage responsiveness and noise equivalent power of the metamaterial-enhanced detector are tested by THz focused optical path and compared with those of the typical pyroelectric detector and the simulated MPA absorptivity. The results indicate that the metamaterial-enhanced detector has a multi-narrowband detection capability at 0.245 THz, 0.295 THz, and 0.38 THz, which is close to the simulated MPA absorptivity. Compared to the typical pyroelectric detector, the split ring hole metamaterial-enhanced detector can simultaneously achieve thermal absorption, thermal conduction, and pyroelectricity in the same MPA structure, providing faster response speed above 100 Hz chopper frequency and two times higher detection sensitivity at multi-narrowband THz frequencies. This research can be used for THz sensing, absorption filtering, biological macromolecule detection, and other applications.

Cardamomin Inhibits the Proliferation and Tumorigenesis of Bladder Cancer by ESR1 in PI3K/AKT Pathway.

Cardamomin has been widely studied in cancer, but its role in cancer bladder cancer has not been mentioned. In this study, we validated the anti-cancer effect of cardamom and whether its potential mechanism is related to the PI3K/AKT pathway. After treating with different doses of cardamomin, the cytotoxicity was studied by CCK8. Secondly, we analyzed the effect of cardamomin on the proliferation, apoptosis and cell movement. Next, we analyzed the regulation of ESR1 by western blot and its impact on the PI3K/AKT pathway. We also transfected ESR1 overexpression and silencing vectors, and verified the transfection efficiency through RT-qPCR. Further, the specific mechanism of the drug's inhibitory effect on bladder cancer was also determined. We constructed the subcutaneous tumor model in vivo. After cardamomin administration, we mainly analyzed the positive expression of KI67 in tumor tissues by immunohistochemistry, and the apoptotic cells in tumor tissues by TUNEL, and related proteins in PI3K/AKT pathway by western blot. In this paper, cardamomin inhibited cell proliferation and invasion ability, blocked the transition of G0/G1 phase to S phase, and increased apoptotic rate of 5637 and HT1376 cells, as well as raised ESR1 expression. Cardamomin exerted anti-tumor effect through PI3K/AKT pathway. In vivo animal experiments indicated the inhibitory effect of cardamomin on subcutaneous implanted tumor. Cardamomin inhibited the positive expression of KI67 and promoted the TUNEL-positive cells in tumor tissues. Consistent with in vitro assay, cardamomin increased the expression of ESR1 and downregulated the PI3K/AKT pathway. Cardamomin has a significant inhibitory effect on bladder cancer, and upregulate the expression of ESR1 in bladder cancer through PI3K/AKT.

Intrinsic Elastomer with Remarkable Dielectric Constant via Elastification of Relaxor Ferroelectric Polymer.

High-dielectric-constant elastomers always play a critical role in the development of wearable electronics for actuation, energy storage, and sensing; therefore, there is an urgent need for effective strategies to enhance dielectric constants. The present methods mainly involve adding inorganic or conductive fillers to the polymer elastomers, however, the addition of fillers causes a series of problems, such as large dielectric loss, increased modulus, and deteriorating interface conditions. Here, the elastification of relaxor ferroelectric polymers is investigated through slight cross-linking, aiming to obtain intrinsic elastomers with high-dielectric constants. By cross-linking of the relaxor ferroelectric polymer poly(vinylidene fluoride-ter-trifluoroethylene-ter-chlorofluoroethylene) with a long soft chain cross-linker, a relaxor ferroelectric elastomer with an enhanced dielectric constant is obtained, twice that of the pristine relaxor ferroelectric polymer and surpassing all reported intrinsic elastomers. This elastomer maintains its high-dielectric constant over a wide temperature range and exhibits robust mechanical fatigue resistance, chemical stability, and thermal stability. Moreover, the ferroelectricity of the elastomer remains stable under strains up to 80%. This study offers a simple and effective way to enhance the dielectric constant of intrinsic elastomers, thus facilitating advancements in soft robots, biosensors, and wearable electronics.

A probe for NIR-II imaging and multimodal analysis of early Alzheimer's disease by targeting CTGF.

To date, earlier diagnosis of Alzheimer's disease (AD) is still challenging. Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an upstream regulator of amyloid-beta (Aß) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than Aß plaque. Herein, we develop a peptide-coated gold nanocluster that specifically targets CTGF with high affinity (KD ~ 21.9 nM). The probe can well penetrate the blood-brain-barrier (BBB) of APP/PS1 transgenic mice at early-stage (earlier than 3-month-old) in vivo, allowing non-invasive NIR-II imaging of CTGF when there is no appearance of Aß plaque deposition. Notably, this probe can also be applied to measuring CTGF on postmortem brain sections by multimodal analysis, including fluorescence imaging, peroxidase-like chromogenic imaging, and ICP-MS quantitation, which enables distinguishment between the brains of AD patients and healthy people. This probe possesses great potential for precise diagnosis of earlier AD before Aß plaque formation.

Assessment of vegetation net primary productivity variation and influencing factors in the Beijing-Tianjin-Hebei region.

Exploring the spatiotemporal variations of vegetation net primary productivity (NPP) and analyzing the relationships between NPP and its influencing factors are vital for ecological protection in the Beijing-Tianjin-Hebei (BTH) region. In this study, we employed the CASA model in conjunction with spatiotemporal analysis techniques to estimate and analyze the spatiotemporal variations of NPP in BTH and different ecological function sub-regions over the past two decades. Subsequently, we established three scenarios (actual, climate-driven and land cover-driven) to assess the influencing factors and quantify their relative contributions. The results indicated that the overall NPP in BTH exhibited a discernible upward trend from 2000 to 2020, with a growth rate of 3.83 gC·m-2a-1. Furthermore, all six sub-regions exhibited an increase. The Bashang Plateau Ecological Protection Zone (BP) exhibited the highest growth rate (5.03 gC·m-2a-1), while the Low Plains Ecological Restoration Zone (LP) exhibited the lowest (2.07 gC·m-2a-1). Geographically, the stability of NPP exhibited a spatial pattern of gradual increase from west to east. Climate and land cover changes collectively increased NPP by 0.04 TgC·a-1 and 0.07 TgC·a-1, respectively, in the BTH region. Climate factors were found to have the greatest influence on NPP variations, contributing 40.49% across the BTH region. This influence exhibited a decreasing trend from northwest to southeast, with precipitation identified as the most influential climatic factor compared to temperature and solar radiation. Land cover change has profound effects on ecosystems, which is an important factor on NPP. From 2000 to 2020, 15.45% area of the BTH region underwent land cover type change, resulting in a total increase in NPP of 1.33 TgC. The conversion of grass into forest brought about the 0.89 TgC increase in NPP, which is the largest of all change types. In the area where land cover had undergone change, the land cover factor has been found to be the dominant factor influencing variations in NPP, with an average contribution of 49.37%. In contrast, in the south-central area where there has been no change in land cover, the residual factor has been identified as the most influential factor influencing variations in NPP. Our study highlights the important role of land cover change in influencing NPP variations in BTH. It also offers a novel approach to elucidating the influences of diverse factors on NPP, which is crucial for the scientific assessment of vegetation productivity and carbon sequestration capacity.

ROS-induced imbalance of the miR-34a-5p/SIRT1/p53 axis triggers chronic chondrocyte injury and inflammation.

Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1ß-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.

Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Introducing the Special Issue Honoring Lihong V. Wang, Pioneer in Biomedical Optics.

The editorial concludes the JBO Special Issue Honoring Lihong V. Wang, outlining Prof. Wang's salient contributions to advancing the field of biomedical optics.