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Introduction: Bisphenol A (BPA) is a widespread environmental pollutant which has serious toxic effects on organisms. One of the crucial trace elements is selenium (Se), whose shortage can harm biological tissues and enhance the toxicity of contaminants, in which apoptosis and autophagy are core events. Objectives: An in vivo model was established to investigate the effects of BPA and low-Se on chicken pancreatic tissue, and identify the possible potential molecular mechanism. Methods: A total of 80 1-day-old broiler chickens (Xinghua Chicken Farm, Harbin, China) were stochastically divided into 4 groups (n = 20/group): Control group, BPA group, low-Se group, and low-Se + BPA group. Pancreatic tissue was collected at day 42 to detect changes in markers. Results: First, the data showed that BPA and low-Se exposure gave rose to structural abnormalities in pancreatic tissue, oxidative stress, mitochondrial dysfunction and homeostasis imbalance, apoptosis and mitophagy. In addition, the co-exposure of BPA and low-Se caused the most serious damage to pancreatic tissue. In terms of mechanism, it was found that apoptosis and mitophagy induced by BPA and low-Se were related to the activation of PTEN/PI3K/AKT/mTOR pathway. Conclusion: In summary, the study found that BPA and low-Se exacerbated mitochondria damage, apoptosis and mitophagy by regulating the PTEN/PI3K/AKT/mTOR pathway.

Abstract Background The majority of robot-assisted total joint arthroplasties necessitate preoperative computed tomography (CT) scans. Incidental findings in these CT scans can introduce complexity into clinical treatment decisions. Consequently, this study sought to document the nature and frequency of incidental findings identified in preoperative CT imaging conducted for robot-assisted total joint arthroplasty, along with their impact on planned surgical procedures. Methods This investigation constitutes a retrospective review encompassing patients who underwent primary robot-assisted total hip arthroplasty between January 2020 and January 2022 at the Second Affiliated Hospital of Xi’an Jiaotong University, the First Affiliated Hospital of Peking University, and Nanfang Hospital. It also includes patients who underwent robot-assisted total knee arthroplasty during the same period at the Second Affiliated Hospital of Xi’an Jiaotong University, the Third Affiliated Hospital of Peking University, Nanfang Hospital, and the Second Affiliated Hospital of Zhejiang University. All CT examinations were initially interpreted by proficient musculoskeletal radiologists. Subsequently, the findings in the examination reports, whether significant or non-significant, were compiled and categorized. Results A total of 218 patients, median age 63, were evaluated; 90 had incidental findings (41.3%), with 56 (25.7%) significant. Males were more likely to have findings (P = 0.001). Nine needed additional imaging, and five required intervention.Our study highlights the impact of unexpected CT findings on surgical planning, which can delay or cancel surgeries and affect patient outcomes. It also urges surgeons to review medical histories and perform thorough examinations before surgery to prevent serious consequences. Conclusions Radiologists often find incidental findings in preoperative CT scans for robot-assisted joint arthroplasty, with a 41.3% incidence rate. About 25.7% of these findings need physician follow-up, and under 5% require intervention, potentially causing delays or cancellations of procedures, while undetected findings could lead to fatal outcomes.Unexpected preoperative CT findings can enhance patient management and prevent complications, necessitating their inclusion in surgical protocols. Systematic assessment improves safety and outcomes, urging surgeons to review medical history and perform thorough examinations pre-surgery. Clinical trial registration Clinical trial registration time: 19/05/2022, clinical trial registration number: ChiCTR2200060115.

Abstract Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Abstract The emerging pseudohalide metal-free perovskite (pseudohalide–MFPs) X-ray detector caters to the demands of timely mobile diagnosis owing to its lightweight, flexibility, and cost-effectiveness. However, the performance of these devices is severely limited by poor X-ray absorption, ultra-wide band gap, relative instability, and their unknown biotoxicity. Herein, we construct heavy atom covalent bonds (C–Br/Cl) on the A-site organic cation to reinforce component coordination to modulate X-ray absorption and band gap in pseudohalide–MFPs and further enhance its stability. Molecular dynamics simulations demonstrate that the introduction of halogen atoms can strengthen hydrogen bonding interactions, thereby improving the coordination between different components. The resultant (MDABCOBr)–NH4(BF4)3 (MDABCO = N-methyl-N’-diazabicyclo[2.2.2]octonium) single crystal significantly increases X-ray absorption cross-section and crystalline density (from 1.728 to 1.950 g cm−3), and synergistically realizes the band nature modulation (from 7.4 to 5.5 eV) and enhanced ionic migration inhibition (628 meV) with optimized stability. As such, our X-ray detectors realized a sensitivity of 2377 μC Gyair −1 cm−2, an ultralow detection limit of 50.1 nGyair s−1, and impressive operation stability. Moreover, cytotoxicity assay confirmed the compatibility of pseudohalide metal-free perovskite. Finally, within this framework, we successfully fabricate the (MDABCOBr)–NH4(BF4)3-based flexible device to create an ideal in vitro wearable X-ray detection.

Background. The development of a hybrid beta-cell replacement approach, referred to as a personalized, transplantable bioartificial pancreas (BAP), holds promise to treat type 1 diabetes (T1D). This interview study aimed to explore patients’ expectations, needs, concerns, and considerations when considering to undergo a BAP transplantation. Research Design and Methods. Semistructured interviews were conducted with 24 participants diagnosed with T1D. Data collection stopped once data saturation was reached. Audio recordings of the interviews were transcribed verbatim. The interviews were independently analyzed by 2 researchers. A qualitative content analysis using an inductive approach was used. Results. Three main themes emerged as follow: (1) hoped-for benefits, (2) concerns and decision-making considerations, and (3) procedural aspects. First, the participants expected benefits across medical, psychological, and social domains. Over these 3 domains, 9 subthemes were identified, including improved clinical outcomes, a cure for diabetes, more headspace, emotional relief, a shift in responsibility, protection of privacy, improved flexibility in daily life, less visible diseases, and improved relationships with others. Second, concerns and considerations about undergoing a BAP transplant comprised adverse events, the functionality of the BAP, the surgery procedure, the biological materials used, the transplant location, and the intrusiveness associated with follow-up care. Finally, procedural considerations included equitable access, patient prioritization, and trust and control. Conclusions. Incorporating insights from this study into the clinical development and implementation of the BAP is crucial to ensure alignment of the product and procedures with the needs and expectations of people with T1D.

A novel (Co40Cr25(FeNi)31Mo4)99·5C0.5 HEA (high entropy alloy) was prepared by vacuum arc melting furnace and hot rolled with a reduction of 20 % at 1100 °C, cold rolled with a reduction of ∼50 %, and then annealed at 800, 850, 900, 950, 1000, and 1100 °C for 6 min, respectively. The effect of annealed on the microstructure evolution and mechanical properties of HEAs were systematically analyzed. The results showed that the HEAs still maintains single FCC(Face-centered cubic) crystal structure after different annealing temperatures. With increasing annealed temperature, the area of abnormal grain gradually decreases and forming equiaxed grain finally. Annealing at lower temperature (800 °C) gives rise to the formation of nanoscale and submicron M23C6 carbide, which hindered the recrystallization of grains and resulting to the higher tensile strength of ∼1352 MPa and lower elongation of ∼37 % when comparing with other annealed HEAs. However, the amount of M23C6 precipitates decreases when the annealing temperature was increased to 1100 °C. At this time, the alloy structure was consisting of recrystallized grains and a large number of annealing twins, and the tensile strength decreased to ∼1062 MPa and the elongation increased to ∼85 %. Due to annealing twins effect and grain refinement, the 1100 °C annealed HEA achieved superior strength-ductility balance (TS × EL) of ∼90.3 GPa%, while the strength-ductility balance (TS × EL) of 800 °C annealed HEA was only ∼50 GPa%. The 1100 °C annealed HEA possesses excellent comprehensive mechanical properties, which is superior to a majority of reported HEAs and conventional metal alloys.

The development of communication technology will promote the application of Internet of Things, and Beyond 5G will become a new technology promoter. At the same time, Beyond 5G will become one of the important supports for the development of edge computing technology. This paper proposes a communication task allocation algorithm based on deep reinforcement learning for vehicle-to-pedestrian communication scenarios in edge computing. Through trial and error learning of agent, the optimal spectrum and power can be determined for transmission without global information, so as to balance the communication between vehicle-to-pedestrian and vehicle-to-infrastructure. The results show that the agent can effectively improve vehicle-to-infrastructure communication rate as well as meeting the delay constraints on the vehicle-to-pedestrian link.

Magnetic graphene (Fe3O4@G) was synthesized as a magnetic solid phase extractor for the extraction and enrichment of organophosphorus pesticides in green tea by chemical coprecipitation method. Based on this, ultra high performance liquid chromatography tandem mass spectrometry method was developed for the determination of 19 organophosphorus pesticide residues in green tea. 40 mg adsorbent and 4 g sodium chloride were used in this experiment with the pH of sample solution at 7 for 20 min extraction time, 3.0 mL acetone desorption. The result showed that the prepared Fe3O4@G material had good stability and reusability with the linear correlation coefficients greater than 0.999 in the range of 5～500 μg/L. The limits of detection (LOD) and the limits of quantitation (LOQ) were 5.0～6.0 μg/kg and 15.0～20.0 μg/kg, respectively. The recoveries were between 61.2% and 94.9% with the relative standard deviations (RSD, n=6) in the range of 2.6%～10.2% when the samples were labeled at 20.0, 40.0 and 200.0 μg/kg. This method was safe and economy with a wide application range, easier control of pretreatment, less amount of organic solvent and reusable materials, which has a good application prospect in the enrichment and separation of pesticides in tea by the magnetic dispersion solid phase extraction technology.

With the rapid development of information communication and mobile device technologies, smart devices have become increasingly popular, providing convenience to households and enhancing the level of intelligence in daily life. This trend is also driving innovation and progress in various fields, including healthcare, transportation, and industry. However, as technology continues to proliferate, network security concerns have become increasingly prominent, making the protection of digital life and data security an urgent priority. Intrusion detection has always played an important role in the field of network security. Traditional intrusion detection systems predominantly rely on anomaly detection technology to identify potential intrusions by detecting abnormal patterns in network traffic. With technological advancements, machine learning-based methods have emerged as the cornerstone of modern intrusion detection, enabling more precise identification of abnormal behaviors and potential intrusions by learning the patterns of normal network traffic. In response to these challenges, this paper introduces an innovative intrusion detection model that amalgamates the Attention-CNN-BiLSTM (ACBL) and Temporal Convolutional Network (TCN) architectures. The ACBL and TCN models excel in processing spatial and temporal features within network traffic data, respectively. This integration harnesses diverse neural network structures to elevate overall model performance and accuracy. Furthermore, a unique approach inspired by dung beetles’ natural behavior, incorporating Tent mapping-enhanced Dung Beetle Optimization Algorithm (TDBO), is leveraged for both optimizing feature selection parameters and searching for optimal model hyperparameters. The feature selection parameters obtained from TDBO are then combined with the importance ranking from the Random Forest algorithm, ensuring optimal features can be better selected to enhance model performance. This paper introduces a novel intrusion detection model, the TDBO-ACBLT model, and validates its performance using the UNSW-NW15 dataset. TDBO excels in feature selection compared to common algorithms and achieves superior parameter optimization accuracy over Harris’s Hawk Optimization (HHO), Particle Swarm Optimization (PSO), and Dung Beetle Optimization (DBO). The proposed model achieves higher accuracy than prevalent machine learning models.

The as-cast (Fe50Mn30Co10Cr10)97C2Mo1 HEA (high entropy alloy) was cold rolled to 90 % (CR90 %), followed by annealing at different temperatures (400 °C, 500 °C, 600 °C). Their microstructure and mechanical properties have been systematically investigated. The results show that this HEA has a single FCC structure, and that annealing at 500 °C and 600 °C leads to the formation of Cr-rich σ phase. The CR90 % HEA exhibits the tensile strength of 1926 MPa and 4 % elongation. However, annealing at 400 °C and 500 °C makes the tensile strength improve to ∼2078 MPa and ∼2060 MPa, respectively, while their plasticity does not change significantly. Annealing at 600 °C results in a significant reduction in the strength (∼1650 MPa) while a slight increase in plasticity. The element segregation and the formation of nano-sized (Fe, Mn)-rich precipitates are contributed to the significant increase in tensile strength of the HEA annealed at 400 °C. Nevertheless, annealing at 600 °C leads to a decrease in the density of defects (e.g. dislocations) caused by cold rolling and the increase in the grain size, which finally resulting in a reduction in strength.

Highlights The classification of 2D perovskite is summarized, and the preparation methods of 2D perovskite according to the requirements of X-ray detection materials are introduced. We analyzed the advantages and insufficiency of different devices and introduced improvement measures, including ion migration, charge transfer performance, stability, and 2D/3D heterojunctions. Finally, we introduced the potential preponderances of 2D perovskite in the scintillation detection field; meanwhile, the main challenges facing the practical application of 2D perovskite X-ray detectors are analyzed.

ObjectiveOsteonecrosis of the femoral head (ONFH) is a common orthopedic condition that will prompt joint dysfunction, significantly impacting patients’ quality of life. However, the specific pathogenic mechanisms underlying this disease remain elusive. The objective of this study is to examine the differentially expressed messenger RNAs (DE mRNAs) and key genes linked to ONFH, concurrently investigating the immune cell infiltration features in ONFH patients through the application of the CIBERSORT algorithm.MethodsMicroarray was applied to scrutinize mRNA expression profiles in both ONFH patients and healthy controls, with data integration sourced from the GEO database. DE mRNAs were screened using the Limma method. The biological functions of DE mRNAs were explored through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Ontology (GO) functional analysis, and Gene Set Enrichment Analysis (GSEA). Additionally, support vector machine–recursive feature elimination (SVM-RFE) and the least absolute shrinkage and selection operator (LASSO) were employed to discern diagnostic biomarkers associated with the disease. Receiver operating characteristic (ROC) analysis was utilized to assess the statistical performance of the feature genes. The validation of key genes was performed using qRT-PCR in bone tissues obtained from ONFH patients and healthy controls. Osteogenic differentiation of BMSC was then performed and detected by alkaline phosphatase staining (ALP) and qRT-PCR to verify the correlation between key genes and osteogenic differentiation. Finally, immune cell infiltration analysis was executed to evaluate immune cell dysregulation in ONFH, concurrently exploring the correlation between the infiltration of immune cells and key genes.ResultsAfter consolidating the datasets, the Limma method revealed 107 DEGs, comprising 76 downregulated and 31 upregulated genes. Enrichment analysis revealed close associations of these DE mRNAs with functions such as cell migration, osteoblast differentiation, cartilage development and extracellular region. Machine learning algorithms further identified APOD, FBXO43 and LRP12 as key genes. ROC curves demonstrated the high diagnostic efficacy of these genes. The results of qRT-PCR showed that the expression levels of key genes were consistent with those of microarray analysis. In addition, the results of in vitro experiments showed that APOD was closely related to osteogenic differentiation of BMSC. Immune infiltration analysis suggested a close correlation between ONFH and imbalances in levels of Neutrophils, Monocytes, Macrophages M2, Dendritic cells activated and Dendritic cells resting.ConclusionAPOD is closely related to osteogenic differentiation of BMSCs and can be used as a diagnostic marker of ONFH. Immune cell infiltration significantly differs between controls and ONFH patients.

Abstract Copper-based metal halides have become important materials in the field of X-ray and photodetection due to their excellent optical properties, good environmental stability and low toxicity. This review presents the progress of research on crystal structure/morphology, photophysics/optical properties and applications of copper-based metal halides. We also discuss the challenges of copper-based metal halides with a perspective of their future research directions. Graphical Abstract

The detection of road damage is highly important for traffic safety and road maintenance. Conventional detection approaches frequently require significant time and expenditure, the accuracy of detection cannot be guaranteed, and they are prone to misdetection or omission problems. Therefore, this paper introduces an enhanced version of the You Only Look Once version 8 (YOLOv8) road damage detection algorithm called RDD-YOLO. First, the simple attention mechanism (SimAM) is integrated into the backbone, which successfully improves the model’s focus on crucial details within the input image, enabling the model to capture features of road damage more accurately, thus enhancing the model’s precision. Second, the neck structure is optimized by replacing traditional convolution modules with GhostConv. This reduces redundant information, lowers the number of parameters, and decreases computational complexity while maintaining the model’s excellent performance in damage recognition. Last, the upsampling algorithm in the neck is improved by replacing the nearest interpolation with more accurate bilinear interpolation. This enhances the model’s capacity to maintain visual details, providing clearer and more accurate outputs for road damage detection tasks. Experimental findings on the RDD2022 dataset show that the proposed RDD-YOLO model achieves an mAP50 and mAP50-95 of 62.5% and 36.4% on the validation set, respectively. Compared to baseline, this represents an improvement of 2.5% and 5.2%. The F1 score on the test set reaches 69.6%, a 2.8% improvement over the baseline. The proposed method can accurately locate and detect road damage, save labor and material resources, and offer guidance for the assessment and upkeep of road damage.

IntroductionIslet xenotransplantation may be a therapeutic option in type 1 diabetes. Recent advances in generating genetically modified source pigs offer advantages as immune suppressants can potentially be eliminated after the transplantation. Therapy monitoring would greatly benefit from noninvasive methods for assessing the viability of transplanted islets. Peptide-based positron emission tomography (PET) targeting the glucagon-like peptide-1 receptor (GLP1R) expression on beta cells may offer a procedure that can directly be translated from an experimental setting to the clinic. The aim of this study was to establish the labeling of the GLP1R ligand [68Ga]Ga-exendin-4, to demonstrate the feasibility of imaging porcine islet xenografts in vivo and to compare signal quality for three different transplantation sites in a mouse model.Materials and methodsMice with engrafted neonatal porcine islet cell clusters (NPICCs) under the kidney capsule, into the inguinal fold, or the lower hindlimb muscle were studied. After reaching normoglycemia, the mice were injected with [68Ga]Ga-exendin-4 for PET data acquisition. Subsequent autoradiography (AR) was used for comparing ex vivo data with in vivo uptake.ResultsNPICCs in the lower right hindlimb muscle could be detected in vivo and in AR. Due to the high background in the kidney and urinary bladder, islets could not be detected in the PET data at transplantation sites close to these organs, while AR showed a clear signal for the islets in the inguinal fold.DiscussionPET with [68Ga]Ga-exendin-4 detects islets transplanted in the hindlimb muscle tissue of mice, offering the potential of longitudinal monitoring of viable porcine islets. Other sites are not suitable for in vivo imaging owing to high activity accumulation of Exendin-4 in kidney and bladder.

Abstract Core decompression (CD) with the elimination of osteonecrotic bone is the most common strategy for treating early-stage nontraumatic osteonecrosis of the femoral head (ONFH). Adjuvant treatments are widely used in combination with CD as suitable methods of therapy. Existing augmentations have to be fabricated in advance. Here, we report a novel injectable glycerin-modified polycaprolactone (GPCL) that can adapt to the shape of the CD cavity. GPCL shows great flowability at 52.6 °C. After solidification, its compressive modulus was 120 kPa at body temperature (37 °C). This excellent characteristic enables the polymer to provide mechanical support in vivo. In addition, GPCL acts as a carrier of the therapeutic agent zoledronic acid (ZA), demonstrating sustained release into the CD region. ZA-loaded GPCL was injected into ONFH lesions to treat early-stage nontraumatic cases. Compared to that in the CD group, CD+ZA-loaded GPCL injection preserved bone density and increased the collagen level in the femoral head. At the interface between the GPCL and CD tunnel wall, osteogenesis was significantly promoted. In addition, morphological evaluations revealed that the femoral heads in the CD+ZA-GPCL group exhibited improved pressure resistance. These results suggest a strategy effective to preserve the bone density of the femoral head, thus decreasing the possibility of femoral head collapse. This novel injectable polymer has, therefore, considerable potential in clinical applications.

Abstract Background Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. Methods Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis. Results Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 μmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis. Conclusions Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs.

Calcineurin inhibitors (CNI) can suppress allo- and autoimmunity by suppressing T cell function but also have anti-proteinuric effects by stabilizing the cellular components of the kidney’s filtration barrier. Therefore, CNI are used in autoimmune kidney diseases with proteinuria. However, the traditional CNI, cyclosporine A and tacrolimus, have a narrow therapeutic range, need monitoring of drug levels, and their use is associated with nephrotoxicity and metabolic alterations. Voclosporin (VOC), a novel CNI, no longer requires drug level monitoring and seems to lack these adverse effects, although hypertension and drug–drug interactions still occur. VOC demonstrated efficacy superior to standard-of-care in controlling active lupus nephritis in the phase 2 AURA-LV and the phase 3 AURORA-1 trials and was approved for the treatment of active lupus nephritis. However, how to implement VOC into the current and changing treatment landscape of lupus nephritis is still debated. Here, we review the unique chemistry, pharmacology, and toxicity profile of VOC, summarize the efficacy and safety data from the AURA-LV and AURORA-1 trials, and discuss the following four possible options to implement VOC into the management of lupus nephritis, namely regarding B cell-targeting therapy with belimumab (BEL). These include: 1. patient stratification to either VOC or BEL, 2. VOC/BEL combination therapy, 3. VOC-BEL sequential therapy, or 4. alternative options for the rapid antiproteinuric effect of VOC.

Nonlinear optical (NLO) imaging has emerged as a promising plant cell imaging technique due to its large optical penetration, inherent 3D spatial resolution, and reduced photodamage; exogenous nanoprobes are usually needed for nonsignal target cell analysis. Here, we report in vivo, simultaneous 3D labeling and imaging of potato cell structures using plasmonic nanoprobe-assisted multimodal NLO microscopy. Experimental results show that the complete cell structure can be imaged via the combination of second-harmonic generation (SHG) and two-photon luminescence (TPL) when noble metal silver or gold ions are added. In contrast, without the noble metal ion solution, no NLO signals from the cell wall were acquired. The mechanism can be attributed to noble metal nanoprobes with strong nonlinear optical responses formed along the cell walls via a femtosecond laser scan. During the SHG-TPL imaging process, noble metal ions that crossed the cell wall were rapidly reduced to plasmonic nanoparticles with the fs laser and selectively anchored onto both sides of the cell wall, thereby leading to simultaneous 3D labeling and imaging of the potato cells. Compared with the traditional labeling technique that needs in vitro nanoprobe fabrication and cell labeling, our approach allows for one-step, in vivo labeling of plant cells, thus providing a rapid, cost-effective method for cellular structure construction and imaging.

The power conversion efficiency (PCE) of perovskite solar cells (PSCs) has increased rapidly to 25.7% in 2022. There is growing curiosity about whether it will increase further up to the PCE limit. Understanding the fundamental energy loss mechanism and targeted treatment is the crux to step forward, especially the definite and management of photons in PSCs. Here, we first briefly review the main modes of photon energy loss in PSCs and illustrate the significance of photon recycling. Next, historical research trials to overcome these loss mechanisms in PSCs are highlighted, including the application of anti-reflection coatings, plasmonic strategies, and the adoption of upconversion and downconversion materials. Finally, we make a brief summary and prospect about strategies that can help to improve photon management in the future.

Objective To analyze the risk factors of elbow stiffness following open reduction and internal fixation of the terrible triad of the elbow joint. Methods A retrospective study was conducted of 100 patients with the terrible triad of the elbow joint, who had been treated at our hospital from January 2015 to December 2018. All patients were treated with a loop plate to repair the ulnar coronoid process. According to the severity of the injury, the radial head was either fixed or replaced, and the lateral collateral ligament was repaired with an anchor. According to the range of motion of the elbow during the last follow‐up, the patients were divided into two groups. The stiffness group (displayed extension–flexion or pronation–supination 1 week (OR = 2.714, 95% CI 1.029–7.159, P = 0.044), and postoperative immobilization time (OR = 3.237, 95% CI 1.176–8.908, P = 0.023) were independent risk factors of elbow stiffness after surgery for the terrible triad of the elbow. Conclusion High‐energy injury, the time from injury to surgery > 1 week, and postoperative joint immobilization time > 2 weeks are the independent risk factors of elbow stiffness after surgery of the terrible triad of the elbow, which should be treated carefully in clinical treatment.

Background: The lack of effective biomarkers makes it difficult to achieve early diagnosis and intervention for osteonecrosis of the femoral head (ONFH). Hence, we aimed to identify novel long noncoding RNA (lncRNA) biomarkers for ONFH.Methods: High-throughput RNA sequencing was performed to detect lncRNA and mRNA expression levels in subchondral bone samples from three patients with ONFH and three patients with femoral neck fractures. Integrated bioinformatics analyses were conducted to identify lncRNAs associated with ONFH development and their potential functions and signaling pathways. A co-expression network was constructed based on the gene time-series expression data in GSE113253. After selecting lncRNA GAS5 as a novel biomarker for ONFH, bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation assays were performed to verify the association between lncRNA GAS5 and osteogenic differentiation. Alkaline phosphatase (ALP) staining and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to measure the osteogenic phenotype and lncRNA GAS5 expression. Finally, for further validation, ONFH rat models were established, and lncRNA GAS5 expression in subchondral bone was detected by RT-qPCR.Results: We identified 126 and 959 differentially expressed lncRNAs and genes, respectively. lncRNA GAS5 expression level was significantly downregulated in patients with ONFH compared to the control group patients. The BMSC osteogenic differentiation assays showed that ALP activity increased gradually from days 3 to 7, while the lncRNA GAS5 expression level was significantly upregulated in the osteogenic differentiation induction groups. Furthermore, in vivo experiments suggested that the bone volume/tissue volume value and trabecular thickness significantly decreased in the ONFH rat model group compared to the control group, whereas the trabecular space significantly increased in the ONFH group compared to the control group. In addition, the lncRNA GAS5 expression level significantly decreased in the ONFH rat model group.Conclusion: The lncRNA GAS5 expression level was highly associated with BMSC osteogenic differentiation and was significantly downregulated in both the subchondral trabecular bone tissue of ONFH patients and ONFH rat models. Therefore, lncRNA GAS5 can serve as an ONFH osteogenic biomarker to provide an effective target for early diagnosis and molecular therapy of ONFH.

The evaluation of pore structure is critical in understanding reservoir characteristics. This study aims to analyze the microscopic pore structure characteristics of tight reservoirs from various provenances through physical property analysis, casting thin sections, scanning electron microscopy (SEM), and constant−rate mercury injection. The pore throat parameters of the Chang 7 reservoir were analyzed and compared to those of the Xin’anbian and the Heshui areas. The results show that intergranular pores dominate the pore type of the Chang 7 reservoir in the Xin’anbian area, followed by feldspathic dissolution pores, with high-necked and tubular throat content caused by weak compaction and dissolution, respectively. On the other hand, feldspar dissolution pores dominate the pore type of the Chang 7 reservoir in the Heshui area, followed by intergranular pores, with a high content of tube−bundle throats caused by dissolution and flake−bent flake throats caused by compaction. The difference in pore parameters between the two blocks is minimal, but the difference in throat parameters is significant. Under the same permeability conditions, the throat radius distribution range of the Chang 7 reservoir samples in the Heshui area is narrower than that in the Xin’anbian area, with tiny throats contributing significantly to reservoir permeability. Sedimentary hydrodynamic conditions and diagenesis are the primary reasons for the differences in the pores, throats, and pore structure parameters of the Chang 7 tight reservoirs.

A low-cost and recyclable multifunctional adsorbent for pesticides was successfully prepared based on herb waste (Angelicae Dahuricae Radix slag), nano-zero-valent iron and graphene oxide (AS/NZVI/GO) via facile one-step pyrolysis approach, and applied to remove pesticides from sewage. The AS/NZVI/GO possesses some excellent merits which are beneficial to achieve high adsorption efficiency, including abundant pore structures, lots of surface functional groups and high specific surface area. The maximum adsorption capacity of AS/NZVI/GO for methomyl, isoprocarb and carbaryl up to 59.13, 21.33 and 61.91 mg·g−1, respectively, proved the good adsorption efficiency of AS/NZVI/GO for pesticides. The adsorption mechanism was mainly associated with pore filling, π-π electron-donor–acceptor interaction, hydrogen bonding and electrostatic interaction. The results showed that the pseudo-second-order kinetic model and Freundlich isotherm model showed a better correlation for the experiment data, indicating that the overall rate of the adsorption process was controlled mainly by physical and chemical adsorption. Furthermore, the reusability experiment exhibited that the removal efficiency of AS/NZVI/GO for three pesticides was more than 70% after five recycles. To sum up, it could conclude that the novel AS/NZVI/GO can be used as an efficient adsorbent for the removal of pesticides.

Alloantigen presentation is an essential process in acute allorejection. In this context, we speculated on a pathogenic role of cathepsin S (Cat-S), a cysteine protease known to promote antigenic peptide loading into MHC class II and to activate protease-activated receptor (PAR)-2 on intrarenal microvascular endothelial and tubular epithelial cells. Single-cell RNA sequencing and immunostaining of human kidney allografts confirmed Cat-S expression in intrarenal mononuclear phagocytes. In vitro, Cat-S inhibition suppressed CD4 + T cell lymphocyte activation in a mixed lymphocyte assay. In vivo, we employed a mouse model of kidney transplantation that showed preemptive Cat-S inhibition significantly protected allografts from tubulitis and intimal arteritis. To determine the contribution of PAR-2 activation, first, Balb/c donor kidneys were transplanted into Balb/c recipient mice without signs of rejection at day 10. In contrast, kidneys from C57BL/6J donor mice revealed severe intimal arteritis, tubulitis, interstitial inflammation, and glomerulitis. Kidneys from Par2-deficient C57BL/6J mice revealed partial protection from tubulitis and lower intrarenal expression levels for Fasl, Tnfa, Ccl5, and Ccr5. Together, we conclude that Cat-S and PAR-2 contribute to immune dysregulation and kidney allograft rejection, possibly involving Cat-S-mediated activation of PAR-2 on recipient parenchymal cells in the allograft.

Accurate measurement of position and attitude information has become the basis of application engineering in related fields. Traditional position and attitude measurement schemes, including lasers, infrared light, etc., often place high demands on the measurement environment. The visual image-based measurement scheme needs to be combined with the actual situation to establish a complex pose calculation model. Therefore, exploring a measurement scheme for efficient solution has become an urgent need in related fields. In this paper, we propose a multi-feature fusion position and attitude measurement neural network (MFNN). We effectively introduce the HOG operator as an image feature and combine it with the original image for a specific ratio. At the same time, we draw on the utilization strategy of feature points in traditional measurement methods. By combining the extracted image feature points with the network, the measurement error of the six-dimensional information is effectively reduced. Based on this, we propose a new type of position and attitude measurement network architecture. MFNN has further improved the accuracy of related measurements.

Neonatal porcine islets-like clusters (NPICCs) are a promising source for cell therapy of type 1 diabetes. Freshly isolated NPICCs are composed of progenitor cells and endocrine cells, which undergo a maturation process lasting several weeks until the normal beta cell function has developed. Here, we investigated the effects of short-chain fatty acids on the maturation of islet cells isolated from two to three day-old piglets. NPICCs were cultivated with acetate, butyrate and propionate (0–2000 µM) for one to eight days. Incubation with butyrate resulted in a significant upregulation of insulin gene expression and an increased beta cell number, whereas acetate or propionate had only marginal effects. Treatment with specific inhibitors of G-protein-coupled receptor GPR41 (β-hydroxybutyrate) and/or GPR43 (GPLG0974) did not abolish butyrate induced insulin expression. However, incubation of NPICCs with class I histone deacetylase inhibitors (HDACi) mocetinostat and MS275, but not selective class II HDACi (TMP269, MC1568) mimicked the butyrate effect on beta cell differentiation. Our study revealed that butyrate treatment has the capacity to increase the number of beta cells, which may be predominantly mediated through its HDAC inhibitory activity. Butyrate and specific class I HDAC inhibitors may represent beneficial supplements to promote differentiation of neonatal porcine islet cells towards beta cells for cell replacement therapies.

Inflammasome-driven release of interleukin(IL)-1β is a central element of many forms of sterile inflammation and has been evident to promote the onset and progression of diabetic kidney disease. We microdissected glomerular and tubulointerstitial samples from kidney biopsies of patients with diabetic kidney disease and found expression of IL-1β mRNA. Immunostaining of such kidney biopsies across a broad spectrum of diabetic kidney disease stages revealed IL-1β positivity in a small subset of infiltrating immune cell. Thus, we speculated on a potential of IL-1β as a therapeutic target and neutralizing the biological effects of murine IL-1β with a novel monoclonal antibody in uninephrectomized diabetic db/db mice with progressive type 2 diabetes- and obesity-related single nephron hyperfiltration, podocyte loss, proteinuria, and progressive decline of total glomerular filtration rate (GFR). At 18 weeks albuminuric mice were randomized to intraperitoneal injections with either anti-IL-1β or control IgG once weekly for 8 weeks. During this period, anti-IL-1β IgG had no effect on food or fluid intake, body weight, and fasting glucose levels. At week 26, anti-IL-1β IgG had reduced renal mRNA expression of kidney injury markers (Ngal) and fibrosis (Col1, a-Sma), significantly attenuated the progressive decline of GFR in hyperfiltrating diabetic mice, and preserved podocyte number without affecting albuminuria or indicators of single nephron hyperfiltration. No adverse effect were observed. Thus, IL-1β contributes to the progression of chronic kidney disease in type 2 diabetes and might therefore be a valuable therapeutic target, potentially in combination with drugs with different mechanisms-of-action such as RAS and SGLT2 inhibitors.

The author studies the asymptotic behavior of minimizers $u_{\varepsilon}$ of a p-energy functional with penalization as $\varepsilon \to 0$. Several kinds of convergence for the minimizer to the p-harmonic map are presented under different assumptions.

The author proves the $W^{1,p}$ convergence of the symmetric minimizers $u_{\varepsilon}=(u_{\varepsilon 1},u_{\varepsilon 2},u_{\varepsilon 3})$ of a p-energy functional as $\varepsilon \to 0$, and the zeros of $u_{\varepsilon 1}^2+u_{\varepsilon 2}^2$ are located roughly. In addition,the estimates of the convergent rate of $u_{\varepsilon 3}^2$ (to $0$) are presented. At last, based on researching the Euler-Lagrange equation of symmetric solutions and establishing its $C^{1,\alpha}$ estimate, the author obtains the $C^{1,\alpha}$ convergence of some symmetric minimizer.

We study the asymptotic behavior of the radial minimizer of a variant of the p-Ginzburg-Landau functional when $p geq n$. The location of the zeros and the uniqueness of the radial minimizer are derived. We also prove the $W^{1,p}$ convergence of the radial minimizer for this functional.

To investigate the long-term outcomes of peritoneal dialysis (PD) patients with diabetes as primary renal disease and patients with diabetes as a comorbid condition.All diabetic patients who commenced PD between January 1, 1995 and June 30, 2012 at Ren Ji Hospital, China were included. Patients were divided into diabetic nephropathy group (DN group) and non-diabetic nephropathy group (NDN group) according to their diagnosis of primary renal disease at the initiation of PD. They were followed until death, cessation of PD, transferred to other centers or to the end of study (June 30, 2013). Outcomes were analyzed by Kaplan-Meier method and Cox regression models.A total of 163 diabetic patients were enrolled in the study, including 121 (74.2%) in DN group and 42 (25.8%) in NDN group. The 1-, 2-, 3- and 5-year patient survival rates were 89%, 78%, 66% and 51% for DN group, and 85%, 63%, 53% and 25% for NDN group, respectively. Kaplan-Meier analysis showed that patients in NDN group had a worse patient survival compared with DN group (log rank 4.830, P=0.028). Patients in NDN group had a marginally shorter peritonitis-free period (log rank 3.297, P=0.069), however, there was no significant difference in technique survival (log rank 0.040, P=0.841). Multivariate Cox regression analysis showed that older age (HR 1.047, 95% CI 1.022-1.073, p

We prove the uniqueness of radial minimizers of a Ginzburg-Landau type functional. We present also an analysis of the the location of the zeros of the radial minimizer.

We study the asymptotic behavior of the regularizable minimizers of a Ginzburg-Landau type functional. We also dicuss the location of the zeroes of the minimizers.

In this article we study the minimizers of the functional $$ E_varepsilon(u,G)={1over p}int_G|abla u|^p+frac{1 over 4varepsilon^p} int_G(1-|u|^2)^2, $$ on the class $W_g={v in W^{1,p}(G,{mathbb R}^2);v|_{partial G}=g}$, where $g:partial G o S^1$ is a smooth map with Brouwer degree zero, and $p$ is greater than 2. In particular, we show that the minimizer converges to the $p$-harmonic map in $C_{hbox{loc}}^{1,alpha}(G,{mathbb R}^2)$ as $varepsilon$ approaches zero.

We consider the functional $$ E_varepsilon(u,G) =frac 1pint_G|abla u|^p +frac{1}{4varepsilon^p}int_G(1-|u|^2)^2 $$ with $p>2$ and $d>0$, on the class of functions $W={u(x)=f(r)e^{idheta} in W^{1,p}(B,C); f(1)=1,f(r)geq 0}$. The location of the zeroes of the minimizer and its convergence as $varepsilon$ approaches zero are established.