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Abstract Herein, we report polyphosphonate covalent organic frameworks (COFs) constructed via P-O-P linkages. The materials are synthesized via a single-step condensation reaction of the charge-assisted hydrogen-bonded organic framework, which is constructed from phenylphosphonic acid and 5,10,15,20‐tetrakis[p‐phenylphosphonic acid]porphyrin and is formed by simply heating its hydrogen-bonded precursor without using chemical reagents. Above 210 °C, it becomes an amorphous microporous polymeric structure due to the oligomerization of P-O-P bonds, which could be shown by constant-time solid-state double-quantum 31P nuclear magnetic resonance experiments. The polyphosphonate COF exhibits good water and water vapor stability during the gas sorption measurements, and electrochemical stability in 0.5 M Na2SO4 electrolyte in water. The reported family of COFs fills a significant gap in the literature by providing stable microporous COFs suitable for use in water and electrolytes. Additionally, we provide a sustainable synthesis route for the COF synthesis. The narrow pores of the COF effectively capture CO2.

Abstract Background Given that viral infections can increase the risk of adverse pregnancy outcomes, such as spontaneous miscarriage, preterm premature rupture of membranes, and preterm birth, the effects of COVID-19, a novel emerging coronavirus disease rapidly spreading globally, on pregnancy outcomes have garnered significant attention. Methods We conducted a review of studies related to pregnant women infected with SARS-CoV-2 over the past five years (December 2019 to April 2023), utilizing search engines such as PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI). This study was registered with PROSPERO with ID: CRD42024540849. Results A total of 218 articles were screened, with 15 studies meeting the inclusion criteria for this research, including 12 cohort studies, one cross-sectional study, one case-control study, and one case series. Six studies found that the preterm birth rate was higher in the infected group compared to the control group; five studies showed that the cesarean section rate was higher in the infected group; three studies found that the APGAR scores of newborns were higher in the control group than in the infected group; three studies indicated that the mortality rate of newborns in the infected group was higher than that in the control group. Conclusions Our retrospective review suggests that compared to pregnant women not infected with SARS-CoV-2, those diagnosed with COVID-19 are more likely to experience adverse outcomes such as preterm birth, cesarean delivery, and low birth weight in newborns.

Abstract The issue of brightness in strong ambient light conditions is one of the critical obstacles restricting the application of augmented reality (AR) and mixed reality (MR). Gallium nitride (GaN)-based micro-LEDs, renowned for their exceptional brightness and stability, are considered the foremost contenders for AR applications. Nevertheless, conventional heteroepitaxial growth micro-LED devices confront formidable challenges, including substantial wavelength shifts and efficiency droop. In this paper, we firstly demonstrated the high-quality homoepitaxial GaN-on-GaN micro-LEDs micro-display, and thoroughly analyzed the possible benefits for free-standing GaN substrate from the material-level characterization to device optoelectronic properties and micro-display application compared with sapphire substrate. The GaN-on-GaN structure exhibits a superior crystal quality with ultra-low threading dislocation densities (TDDs) of ~ 105 cm−2, which is three orders of magnitude lower than that of GaN-on-Sapphire. Through an in-depth size-dependent optoelectronic analysis of blue/green emission GaN-on-GaN/ Sapphire micro-LEDs from 100 × 100 shrink to 3 × 3 μm2, real that a lower forward voltage and series resistance, a consistent emission wavelength (1.21 nm for blue and 4.79 nm for green @ 500 A/cm2), coupled with a notable reduction in efficiency droop ratios (15.6% for blue and 28.5% for green @ 500 A/cm2) and expanded color gamut (103.57% over Rec. 2020) within GaN-on-GaN 10 μm micro-LEDs. Last but not least, the GaN-on-GaN micro-display with 3000 pixels per inch (PPI) showcased enhanced display uniformity and higher luminance in comparison to its GaN-on-Sapphire counterpart, demonstrating significant potentials for high-brightness AR/MR applications under strong ambient light.

Abstract Predicting the corrosion rate for soil-buried steel is significant for assessing the service-life performance of structures in soil environments. However, due to the large amount of variables involved, existing corrosion prediction models have limited accuracy for complex soil environment. The present study employs three machine learning (ML) algorithms, i.e., random forest, support vector regression, and multilayer perception, to predict the corrosion current density of soil-buried steel. Steel specimens were embedded in soil samples collected from different regions of the Wisconsin state. Variables including exposure time, moisture content, pH, electrical resistivity, chloride, sulfate content, and mean total organic carbon were measured through laboratory tests and were used as input variables for the model. The current density of steel was measured through polarization technique, and was employed as the output of the model. Of the various ML algorithms, the random forest (RF) model demonstrates the highest predictability (with an RMSE value of 0.01095 A/m2 and an R 2 value of 0.987). In light of the feature selection method, the electrical resistivity is identified as the most significant feature. The combination of three features (resistivity, exposure time, and mean total organic carbon) is the optimal scenario for predicting the corrosion current density of soil-buried steel.

In order to solve the problem of difficult deployment of existing deep learning-based defect detection models in terminal equipment with limited computational capacity, a lightweight steel surface defect testing model LSKA-YOLOv8 was proposed based on the YOLOv8n target detection framework. The model uses KernelWarehouse Conv (KWConv) with lower computational volumes, which significantly reduces the required computational resources. By updating the traditional Feature Pyramid Network (FPN) structure to Bi-directional Feature Pyramid Network (BiFPN), enhance the capture of contextual information and reduce the number of parameters of the model. In addition, the Spatial Pyramid Pooling Fast (SPPF) module was replaced with a more accurate Receptive Field Block (RFB) module, expanding the model’s sensory field and improving characteristic representation. At the same time, the Large Separable Kernel Attention (LSKAttention) module was introduced in the detection head, effectively enhancing the understanding and capture of the target characteristics, thus significantly improving the overall detection performance. Experiments on the NEU-DET dataset showed that the average accuracy of LSKA-YOLO increased by 4.4% on the map@0.5 indicator compared to the benchmark model, while the number of parameters and calculations of the model decreased by 26.7% and 50%, respectively. Provides valuable references and practical applications for deployment of defect detection models on computing-resource-limited terminal devices.

To clarify the mechanical characteristics of tight sandstone in the Cretaceous Bashijiqike Formation of Kuqa Depression in Tarim Basin, and address field issues in deep and ultra-deep oil and gas exploration and development, triaxial compression experiments were used to quantitatively study the patterns of changes in rock mechanical properties influenced by confining pressure, fluid, and loading rate, with a preliminary analysis of their causes. The results showed that the maximum principal stress difference and elastic modulus of the sandstone samples increased significantly with confining pressure. The micro-reason was that the increase in confining pressure reduced the distance between particles inside the rock, enhancing the rock's cohesion and making particle dispersion less likely. Sandstone samples exhibited a progression from brittleness under low confining pressure to brittle-ductile transformation, and to ductile deformation under high confining pressure. Compared with dry sandstone samples, the reduction in the elastic modulus of samples soaked in pure water, 150 g/L solution, 250 g/L solution, and 350 g/L solution were 67.71%, 61.45%, 64.69%, and 57.32%, respectively, with pure water soaking causing the greatest reduction. Increasing fluid salinity could mitigate the weakening trend in rock mechanical parameters. Crystallization on crystal surfaces and changes in the electric double layer thickness were important controlling factors for these patterns. At lower loading rates, the values for maximum principal stress difference, elastic modulus, and Poisson's ratio of the sandstone samples were smaller, but they increased faster with increasing loading rates. When the loading rate reached a certain critical value (around 0.05 mm/min in this experiment), the rate of increase in rock mechanical parameters slowed down.

To enhance the development efficiency of ultra-deep fault-controlled carbonate reservoirs, large-scale rock mechanical experiments were conducted to reveal the deformation and connectivity mechanisms of high-angle to near-vertical fault surfaces. Based on the mechanical and flow coupling principles of high-pressure water injection production, geomechanical modeling was employed to clarify the current in-situ stress field and fault activity distribution patterns in fault-controlled carbonate reservoirs. Significant differences were found in fault activities in different directions and in the connectivity of fracture and cavity bodies in different parts. The development effects of different wellbore trajectories were then analyzed, and an integrated geological and engineering working method was proposed to scientifically guide the design of wellbore trajectories and the optimization of water injection schemes. The results show: ① Large-scale fractured bodies and high-angle fracture systems in strike-slip fault deformation are key factors affecting reservoir quality. High-pressure water injection can activate existing fractures on one hand, and on the other hand, it can extend and expand based on existing fractures, even generating new fractures, promoting the interconnection of fault-controlled fracture and cavity bodies in both vertical and horizontal directions; ② During the high-pressure water injection process, coupling changes between mechanics and flow occur inside the fault body, improving the seepage environment, and increasing oil and gas recovery rate through cyclic lifting; ③ According to the shape and the occurrence of the fault body, and the dynamic shear deformation connectivity of the fault surface, the best well point and well trajectory for directional wells can be selected, and the water injection scheme can be optimized; ④ In the fault-controlled oil reservoir test area of Tarim Basin, the recovery rate was increased by 5% through high-pressure water injection. This method provides a good theoretical basis and technical support for the efficient development of ultra-deep fault-controlled reservoirs.

To optimize the identification of sweet spots with natural fracture development in ultra-deep tight sandstone reservoirs of Cretaceous in the Kuqa Depression, Tarim Basin, this study systematically analyzed the differences in rock mechanical properties across various sedimentary microfacies in the BZ gas field. Utilizing data from outcrops, rock slices, imaging logging, and other sources, a method for optimizing the rock mechanics parameter model of reservoirs was proposed, which enhanced the prediction accuracy of natural fractures within 200 m around the wellbore. Key findings of the research include: (1) In the third member of the Cretaceous Bashijiqike Formation in the BZ gas field, different sedimentary microfacies and the same microfacies at different positions had differences in rock composition and rock assemblages (including debris content, matrix content, grain size sorting, sand-to-mud ratio, and sand-mudstone combinations). These variations affected the reservoir's Poisson's ratio and Young's modulus, and different microfacies had different rock mechanical parameters. (2) The extent of fracture development differed across various sedimentary microfacies of sand bodies. Fractures were most developed in the underwater distributary channel sandstones at the fan delta front, making them more prone to fracturing compared to the interdistributary bay microfacies and distributary channel microfacies on the delta plain. (3) By further establishing three-dimensional models of different microfacies based on geometric parameters derived from outcrops, it would be feasible to optimize sedimentary microfacies models and rock mechanical parameter models around the wellbore, thereby facilitating more accurate fracture prediction.

Efficient exploration and development of ultra-deep oil and gas reservoirs are key objectives in current global energy geological research. The concept of "geomechanical strata and oil and gas exploration and development" represents a cutting-edge research area internationally. Establishing an effective method for dividing geomechanical layers holds both theoretical and practical significance for the efficient exploration and economical development of ultra-deep oil and gas reservoirs. Currently, the state of in-situ stress affects the effectiveness of natural fractures, while the development and distribution of fractures impact the mechanical properties of rocks, which influence the the distribution of in-situ stress. However, the existing "rock mechanical stratigraphy theory" fails to comprehensively cover the coupling relationships among these three factors. In response, this study introduced a method for the quantitative division of geomechanical strata based on six parameters: minimum horizontal principal stress, difference in horizontal stress, elastic modulus, angle between the current dominant stress orientation and the natural fracture orientation, natural fracture density, and stress concentration factor. An analysis of well W in the Dabei area of the Kelasu structural belt, Kuqa Depression, Tarim Basin, demonstrated that the target layers at the Cretaceous Bashijiqike Formation exhibited strong vertical geomechanical heterogeneity. The geomechanical strata of the reservoir correlated well with the development sections of the gas layers. Therefore, with the results of geomechanical strata division, it is possible to guide the optimization of sweet spots in ultra-deep oil and gas reservoirs.

Abstract Electrocaloric refrigeration which is environmentally benign has attracted considerable attention. In distinction to ferroelectric materials, which exhibit an extremely high positive electrocaloric effect near the Curie temperature, antiferroelectric materials represented by PbZrO3 have a specific negative electrocaloric effect, i.e., electric field decreases the temperature of the materials. However, the explanation of the microscopic mechanism of the negative electrocaloric effect is still unclear, and further research is still needed to provide a theoretical basis for the negative electrocaloric effect enhancement. Herein, the antiferroelectric phase-field model has been proposed to design polar boundaries enhancing antiferroelectric negative electrocaloric performance in PbZrO3-based materials. Based on this, we have simulated the polarization response and domain switching process of the temperature and electric field-induced antiferroelectric—ferroelectric phase transition. It is shown that the temperature range tends to increase as the density of polar boundaries increases from the antiferroelectric stripe domain, polymorphic domain to the nanodomain. Among them, the peak adiabatic temperature change of antiferroelectric nanodomains can reach −13.05 K at 84 kV/cm, and a wide temperature range of about 75 K can be realized at 42 kV/cm. We expect these discoveries to spur further interest in the potential applications of antiferroelectric materials for next-generation refrigeration devices.

Abstract Background Angina is a crucial risk signal for cardiovascular disease. However, few studies have evaluated the effects of ambient air pollution exposure on angina. Objective We aimed to explore the short-term effects of air pollution on hospitalization for angina and its lag effects. Methods We collected data on air pollutant concentrations and angina hospitalizations from 2013 to 2020. Distributed lag nonlinear model (DLNM) was used to evaluate the short-term effects of air pollutants on angina hospitalization under different lag structures. Stratified analysis by sex, age and season was obtained. Results A total of 39,110 cases of angina hospitalization were included in the study. The results showed a significant positive correlation between PM2.5, SO2, NO2, and CO and angina hospitalization. Their maximum harmful effects were observed at lag0-7 (RR = 1.042; 95% CI: 1.017, 1.068), lag0-3 (RR = 1.067; 95% CI: 1.005, 1.133), lag0-6 (RR = 1.078; 95% CI: 1.041, 1.117), and lag0-6 (RR = 1.244; 95% CI: 1.109, 1.397), respectively. PM10 did not have an overall risk effect on angina hospitalization, but it did have a risk effect on women and the elderly. O3 was significantly negatively correlated with angina hospitalization, with the most pronounced effect observed at lag0-6 (RR = 0.960; 95% CI: 0.940, 0.982). Stratified analysis results showed that women and the elderly were more susceptible to pollutants, and the adverse effects of pollutants were stronger in the cold season. Conclusion Short-term exposure to PM2.5, SO2, NO2, and CO increases the risk of hospitalization for angina.

Abstract Ulcerative colitis (UC) is a persistent inflammatory condition that specifically targets the colon and rectum. Existing therapies fail to adequately address the clinical requirements of people suffering from this ailment. Despite the acknowledged potential of nanomedicines in the field of anti-inflammatory treatment, their widespread use in clinical settings is impeded by their expensive nature and the uncertainty surrounding their safety profiles. This study illustrates that two naturally occurring phytochemicals, Costunolide (COS) and Glycyrrhizic acid (GA), form carrier-free, multifunctional spherical nanoparticles (NPs) through noncovalent interactions, such as π–π stacking and hydrogen bonding. The COS-GA NPs displayed a synergistic anti-inflammatory effect, providing much more evidently improved therapeutic benefits for dextran sodium sulfate (DSS)-induced UC mice due to more effective reduction in inflammation and oxidative stress than did equal dosages of COS or GA used alone. In addition, COS-GA NPs have biocompatibility and biosafety properties unique to them. This study will serve as affirmation of the potential of COS-GA NPs as innovative natural anti-inflammatory and antioxidant activities and also such agents as drug discovery in UC, leading possibly to better outcomes in people living with this disabling condition.

Posttraumatic osteoarthritis (PTOA) patients are often diagnosed by X-ray imaging at a middle-late stage when drug interventions are less effective. Early PTOA is characterized by overexpressed matrix metalloprotease 13 (MMP13). Herein, we constructed an integrated diagnosis and treatment micelle modified with MMP13 enzyme-detachable, cyanine 5 (Cy5)-containing PEG, black hole quencher-3 (BHQ3), and cRGD ligands and loaded with siRNA silencing MMP13 (siM13), namely ERMs@siM13. ERMs@siM13 could be cleaved by MMP13 in the diseased cartilage tissues to detach the PEG shell, causing cRGD exposure. Accordingly, the ligand exposure promoted micelle uptake by the diseased chondrocytes by binding to cell surface αvβ3 integrin, increasing intracellular siM13 delivery for on-demand MMP13 downregulation. Meanwhile, the Cy5 fluorescence was restored by detaching from the BHQ3-containing micelle, precisely reflecting the diseased cartilage state. In particular, the intensity of Cy5 fluorescence generated by ERMs@siM13 that hinged on the MMP13 levels could reflect the PTOA severity, enabling the physicians to adjust the therapeutic regimen. Finally, in the murine PTOA model, ERMs@siM13 could diagnose the early-stage PTOA, perform timely interventions, and monitor the OA progression level during treatment through a real-time detection of MMP13. Therefore, ERMs@siM13 represents an appealing approach for early-stage PTOA theranostics.

This paper presents a selective review of statistical computation methods for massive data analysis. A huge amount of statistical methods for massive data computation have been rapidly developed in the past decades. In this work, we focus on three categories of statistical computation methods: (1) distributed computing, (2) subsampling methods, and (3) minibatch gradient techniques. The first class of literature is about distributed computing and focuses on the situation, where the dataset size is too huge to be comfortably handled by one single computer. In this case, a distributed computation system with multiple computers has to be utilized. The second class of literature is about subsampling methods and concerns about the situation, where the blacksample size of dataset is small enough to be placed on one single computer but too large to be easily processed by its memory as a whole. The last class of literature studies those minibatch gradient related optimization techniques, which have been extensively used for optimizing various deep learning models.

Post translational modifications (PTMs) can change the properties of a protein by covalent addition of functional groups to one or more amino acids, and influence almost all aspects of normal cell biology and pathogenesis. Lactylation is a novel identified PTM, and has been found in both histone and non-histone proteins. Since associated with the end product of glycolysis-- lactate, lactylation modification could provide a new perspective for understanding the relationship between metabolic reprogramming and epigenetic modifications. Accumulated evidences suggest that lactylation play important roles in tumor progression and links to poor prognosis in clinical studies. Histone lactylation can affect gene expression in tumor cells and immunological cells, further promoting tumor progression and immune suppression. Lactylation on non-histone proteins can also regulate tumor progression and drug resistance. In this review, we aimed to summarize the roles of lactylation in cancer progression, microenvironment interactions and immune suppression, try to identify new molecular targets for cancer therapy and provide a new direction for combined targeted therapy and immunotherapy.

Abstract Background Q fever, caused by the zoonotic pathogen Coxiella burnetii, exhibits a worldwide prevalence. In China, Q fever is not recognized as a notifiable disease, and the disease is overlooked and underestimated in clinical practice, leading to diagnostic challenges. Case presentation We present a case series of three patients diagnosed with persistent Q fever between 2022 and 2023. The average age of our three cases was 63.33 years old, consisting of two males and one female. The medical history of the individuals included previous valve replacement, aneurysm followed by aortic stent-graft placement and prosthetic hip joint replacement. At the onset of the disease, only one case exhibited acute fever, while the remaining two cases were devoid of any acute symptoms. The etiology was initially overlooked until metagenomic next-generation sequencing test identified Coxiella burnetii from the blood or biopsy samples. Delayed diagnosis was noted, with a duration ranging from three months to one year between the onset of the disease and its confirmation. The epidemiological history uncovered that none of the three cases had direct exposure to domestic animals or consumption of unpasteurized dairy products. Case 1 and 2 resided in urban areas, while Case 3 was a rural resident engaged in farming. All patients received combination therapy of doxycycline and hydroxychloroquine, and no recurrence of the disease was observed during the follow-up period. Conclusion Q fever is rarely diagnosed and reported in clinical practice in our country. We should be aware of persistent Q fever in high-risk population, even with unremarkable exposure history. Metagenomic next-generation sequencing holds great potential as a diagnostic tool for identifying rare and fastidious pathogens such as Coxiella burnetii.

During checking continuous waveform record, it was found that some stations of Tianjin such as EWZ were significantly affected by one unknown noise, and EWZ station was the most seriously affected. Long term observations had also found that this noise cannot be observed for uncertainly several days each year. This noise was all year round and did not change with day and night time, and it had been existed for many years. This noise was different from typical environmental background noise and had some fixed characteristics. This article studied the noise from several aspects such as its own characteristic, its coverage of influence, spectral characteristics, and impact on earthquake records. The research has shown that the noise was not affected by natural factors such as weather and season, and had a characteristic of amplitude decreasing as the distance increasing from EWZ station. The main frequency of this noise ranged 1～2 Hz. The impact of noise was relatively wide and it can be recorded by 12 surrounding stations, with YGZ station being the farthest and approximately 58 km away from EWZ station. Through polarization analysis, it was found that the propagation of noise had a specific directionality, so it is preliminary judged that this noise had the characteristic of fixed source noise. This noise will have an impact on seismic records, reducing the seismic phase pickup rate, and even completely submerging it in the noise. Frequency filtering can improve it.

Abstract Background Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. Methods To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy. Results Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair. Conclusions We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials.

Compared to bioactive glass 45S5, bioactive glass 1393 has shown greater potential in activating tissue cells and promoting angiogenesis for bone repair. Nevertheless, the effect of bioactive glass 1393 in the context of wound healing remains extensively unexplored, and its mechanism in wound healing remains unclear. Considering that angiogenesis is a critical stage in wound healing, we hypothesize that bioactive glass 1393 may facilitate wound healing through the stimulation of angiogenesis. To validate this hypothesis and further explore the mechanisms underlying its pro-angiogenic effects, we investigated the impact of bioactive glass 1393 on wound healing angiogenesis through both in vivo and in vitro studies. The research demonstrated that bioactive glass 1393 accelerated wound healing by promoting the formation of granulation, deposition of collagen, and angiogenesis. The results of Western blot analysis and immunofluorescence staining revealed that bioactive glass 1393 up-regulated the expression of angiogenesis-related factors. Additionally, bioactive glass 1393 inhibited the expression of ROS and P53 to promote angiogenesis. Furthermore, bioactive glass 1393 stimulated angiogenesis through the P53 signaling pathway, as evidenced by P53 activation assays. Collectively, these findings indicate that bioactive glass 1393 accelerates wound healing by promoting angiogenesis via the ROS/P53/MMP9 signaling pathway.

Laser powder bed fusion is capable of fabricating aluminum (Al) alloy parts with great geometrical flexibility and rapid prototyping for various industries. However, high strength Al alloys generally suffer from solidification cracks due to the steep thermal gradient associated with the laser fusion process. Here, we report several strategies to mitigate the hot crack susceptibility of a high strength Al92Ti2Fe2Co2Ni2 alloy. Routine processing parameter optimization based on varying laser power and scanning speed has to trade off porosity for producing crack-free parts, making it not suitable for load-bearing structural applications. Furthermore, secondary printing parameters, including laser strip length, laser defocus, scanning strategies, etc., improved printability but were insufficient to eliminate all the cracks. Crack morphology and residual stress measurements indicate that the cracks are generated in the solid state driven by large tensile residual stress, instead of solidification cracking or liquation cracking. Thus, an attempt was made to alleviate the residual stress in a controlled manner. By properly introducing a compliant, sacrificial, scaffold support structure to regulate crack propagation, near fully dense, crack-free parts could be successfully printed. The results were further verified by micro computed tomography, showing that cracking could be arrested in the support before propagating through the parts. This method can be readily applied to other alloy systems without modifying the chemistry.

Abstract The coronavirus disease (COVID-19) pandemic has continued for 5 years. Sporadic cases continue to occur in different locations. Type 2 diabetes mellitus (T2DM) is associated with a high risk of a poor prognosis in patients with COVID-19. Successful control of blood glucose levels can effectively decrease the risks of severe infections and mortality. However, the effects of different treatments were reported differently and even adversely. This retrospective study included 4,922 patients who have been diagnosed as COVID-19 and T2DM from 138 Hubei hospitals. The clinical characteristics and outcomes were compared and calculated their risk for death using multivariate Cox regression and Kaplan–Meier curves. After adjustment of age, sex, comorbidities, and in-hospital medications, metformin and alpha-glucosidase inhibitor (AGI) use performed lower all-cause mortality (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI]: 0.24–0.71; p = 0.001 for metformin; 0.53, 0.35–0.80, p = 0.002 for AGIs), while insulin use was associated with increased all-cause mortality (adjusted HR, 2.07, 95% CI, 1.61–2.67, p

Abstract Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

Abstract The pathogenesis of major depressive disorder (MDD) involves lipid metabolism. Our earlier research also revealed that MDD patients had much lower total cholesterol (TC) concentrations than healthy controls (HCs). However, it is still unclear why TC decreased in MDD. Here, based on the Ingenuity Knowledge Base’s ingenuity pathway analysis, we found that sodium voltage-gated channel alpha subunit 11A (SCN11A) might serve as a link between low lipid levels and MDD. We analyzed the TC levels and used ELISA kits to measure the levels of SCN11A in the serum from 139 MDD patients, and 65 HCs to confirm this theory and explore the potential involvement of SCN11A in MDD. The findings revealed that TC levels were considerably lower and SCN11A levels were remarkably increased in MDD patients than those in HCs, while they were significantly reversed in drug-treatment MDD patients than in drug-naïve MDD patients. There was no significant difference in SCN11A levels among MDD patients who used single or multiple antidepressants, and selective serotonin reuptake inhibitors or other antidepressants. Pearson correlation analysis showed that the levels of TC and SCN11A were linked with the Hamilton Depression Rating Scales score. A substantial association was also found between TC and SCN11A. Moreover, a discriminative model made up of SCN11A was discovered, which produced an area under a curve of 0.9571 in the training set and 0.9357 in the testing set. Taken together, our findings indicated that SCN11A may serve as a link between low lipid levels and MDD, and showed promise as a candidate biomarker for MDD.

Introduction: Neuroinflammation and autophagy are implicated in stress-related major depressive disorder (MDD), but the underlying molecular mechanisms remain largely unknown. Objectives: Here, we identified that MDD regulated by HMGB1/STAT3/p65 axis mediated microglial activation and autophagy for the first time. Further investigations were performed to uncover the effects of this axis on MDD in vivo and in vitro. Methods: Bioinformatics analyses were used to re-analysis the transcriptome data from the dorsolateral prefrontal cortex (dlPFC) of post-mortem male MDD patients. The expression level of HMGB1 and its correlation with depression symptoms were explored in MDD clinical patients and chronic social defeat stress (CSDS)-induced depression model mice. Specific adeno-associated virus and recombinant (r)HMGB1 injection into the medial PFC (mPFC) of mice, and pharmacological inhibitors with rHMGB1 in two microglial cell lines exposed to lipopolysaccharide were used to analyze the effects of HMGB1/STAT3/p65 axis on MDD. Results: The differential expression of genes from MDD patients implicated in microglial activation and autophagy regulated by HMGB1/STAT3/p65 axis. Serum HMGB1 level was elevated in MDD patients and positively correlated with symptom severity. CSDS not only induced depression-like states in mice, but also enhanced microglial reactivity, autophagy as well as activation of the HMGB1/STAT3/p65 axis in mPFC. The expression level of HMGB1 was mainly increased in the microglial cells of CSDS-susceptible mice, which also correlated with depressive-like behaviors. Specific HMGB1 knockdown produced a depression-resilient phenotype and suppressed the associated microglial activation and autophagy effects of CSDS-induced. The effects induced by CSDS were mimicked by exogenous administration of rHMGB1 or specific overexpression of HMGB1, while blocked by STAT3 inhibitor or p65 knockdown. In vitro, inhibition of HMGB1/STAT3/p65 axis prevented lipopolysaccharide-induced microglial activation and autophagy, while rHMGB1 reversed these changes. Conclusion: Our study established the role of microglial HMGB1/STAT3/p65 axis in mPFC in mediating microglial activation and autophagy in MDD.

Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current clinical treatments remain inadequate for effectively managing OA. Organoids, miniature 3D tissue structures from directed differentiation of stem or progenitor cells, mimic native organ structures and functions. They are useful for drug testing and serve as active grafts for organ repair. However, organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth. Hydrogel microspheres, with tunable physical and chemical properties, show promise in cartilage tissue engineering by replicating the natural microenvironment. Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration, we developed a novel RGD-SF-DNA hydrogel microsphere (RSD-MS) via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA. The RSD-MSs exhibited uniform size, porous surface, and optimal swelling and degradation properties. In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells (BMSCs) proliferation, adhesion, and chondrogenic differentiation. Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis. Moreover, in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors (COPs) significantly enhanced cartilage regeneration. In conclusion, RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids, offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.

Pancreatic cancer (PC) is a highly aggressive and lethal malignancy characterized by a complex tumor microenvironment (TME) and immunosuppressive features that limit the efficacy of existing treatments. This paper reviews the potential of combining ultrasound with macrophage exhaustion in the treatment of pancreatic cancer. Macrophages, particularly tumor-associated macrophages (TAMs), are crucial in pancreatic cancer progression and immune escape. Prolonged exposure to the immunosuppressive TME leads to macrophage exhaustion, reducing their anti-tumor ability and instead promoting tumor growth. The CSF1/CSF1R signaling pathway is key in macrophage recruitment and functional regulation, making it an effective target for combating macrophage exhaustion. Ultrasound technology not only plays a significant role in diagnosis and staging but also enhances therapeutic efficacy by guiding radiofrequency ablation (RFA) and percutaneous alcohol injection (PEI) in combination with immunomodulators. Additionally, ultrasound imaging can monitor the number and functional status of TAMs in real-time, providing a basis for optimizing treatment strategies. Future studies should further investigate the combined use of ultrasound and immunomodulators to refine treatment regimens, address challenges such as individual variability and long-term effects, and offer new hope for pancreatic cancer patients.

This study investigates leakage mechanisms in vertical GaN-on-GaN Schottky barrier diodes (SBDs) and demonstrates effective mitigation strategies. The fabricated devices exhibit low reverse leakage current (1 × 10−5 A/cm2 at −200 V) and a high Ion/Ioff ratio (∼1010), surpassing the performance of GaN SBDs on foreign substrates. We elucidate dominant leakage mechanisms—thermionic emission, Poole–Frenkel emission, and variable-range hopping—and their evolution with temperature and bias. Optimized fabrication processes, including defect etching and a novel dual-layer passivation technique, achieve over a 1000-fold reduction in leakage current.

Cardiomyopathies, encompassing hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), constitute a diverse spectrum of heart muscle diseases that often culminating in heart failure (HF). The inherent molecular heterogeneity of these conditions has implications for prognosis and therapeutic strategies.Publicly available microarray and RNA sequencing (RNA-seq) data sets of HCM (n = 106 from GSE36961) and DCM (n = 18 from GSE135055 and 166 from GSE141910) patients were employed for our analysis. The Non-negative Matrix Factorization (NMF) algorithm was applied to explore the molecular stratification within HCM and DCM, and enrichment analysis was performed to delineate their biological characteristics. By integrating bulk and single-nucleus RNA-seq (snRNA-seq) data, we identified a potential biomarker for HCM progression and cardiac fibrosis, which was subsequently validated using mendelian randomization and in vitro.Our application of NMF identified two distinct molecular clusters. Particularly, a profibrotic, heart failure with reduced ejection fraction (HFrEF)-resembling Cluster 1 emerged, characterized by diminished expression of CORIN and a high degree of fibroblast activation. This cluster also exhibited lower left ventricular ejection fraction (LVEF) and worse prognostic outcomes, establishing the significance of this molecular subclassification. We further found that overexpression of CORIN could mitigate TGFβ1-induced expression of col1a1 and α-SMA in neonatal rat cardiac fibroblasts.Our results indicated the heterogeneity of HCM population, and further evidenced the participation of corin in the progression of HCM, DCM and HFrEF. Nevertheless, our study is constrained by the lack of corresponding clinical data and experimental validation of the identified subtypes. Therefore, further studies are warranted to elucidate the downstream pathways of corin and to validate these findings in independent patient cohorts.

Lung cancer is one of the most common malignant tumours worldwide and its high mortality rate makes it a leading cause of cancer-related deaths. To address this daunting challenge, we need a comprehensive understanding of the pathogenesis and progression of lung cancer in order to adopt more effective therapeutic strategies. In this regard, integrating multi-omics data of the lung provides a highly promising avenue. Multi-omics approaches such as genomics, transcriptomics, proteomics, and metabolomics have become key tools in the study of lung cancer. The application of these methods not only helps to resolve the immunotherapeutic mechanisms of lung cancer, but also provides a theoretical basis for the development of personalised treatment plans. By integrating multi-omics, we have gained a more comprehensive understanding of the process of lung cancer development and progression, and discovered potential immunotherapy targets. This review summarises the studies on multi-omics and immunology in lung cancer, and explores the application of these studies in early diagnosis, treatment selection and prognostic assessment of lung cancer, with the aim of providing more personalised and effective treatment options for lung cancer patients.

Summary: Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.

ObjectiveThis study aimed to explore the relationship between smoking status and the interval to brain metastasis in patients with non-small cell lung cancer (NSCLC) and its impact on survival time after brain metastasis.MethodsData were collected from patients with NSCLC with brain metastases who were treated at our centre between January 2005 and December 2017. Clinical indices such as clinicopathological features and smoking status were recorded, and patients were followed up until 1 September 2022. Based on our inclusion and exclusion criteria, 461 patients were analysed and matched using 1:1 propensity score matching. Three balanced groups were formed: non-smoking (n = 113), smoking cessation (n = 113), and smoking (n = 113). The interval to brain metastasis and overall survival were compared between the groups.ResultsThere was a statistically significant difference in the interval to brain metastasis between the non-smoking and smoking cessation groups (p = 0.001), as well as between the non-smoking and smoking groups (p < 0.001). However, the difference between the smoking cessation and smoking groups was not statistically significant (p = 0.106). Multivariate and univariate analyses identified smoking status, clinical stage, lung cancer surgery, chemotherapy, and chest radiotherapy as independent predictors of the interval to brain metastasis. Additionally, the multivariate analysis showed that smoking status, driver gene mutations, and chest radiotherapy independently influenced survival after brain metastasis.ConclusionSmoking status in patients with NSCLC affects the interval to brain metastasis and survival after brain metastasis.

BackgroundColorectal cancer (CRC) poses a global health threat, with the oral microbiome increasingly implicated in its pathogenesis. This study leverages Mendelian Randomization (MR) to explore causal links between oral microbiota and CRC using data from the China National GeneBank and Biobank Japan. By integrating multi-omics approaches, we aim to uncover mechanisms by which the microbiome influences cellular metabolism and cancer development.MethodsWe analyzed microbiome profiles from 2017 tongue and 1915 saliva samples, and GWAS data for 6692 CRC cases and 27178 controls. Significant bacterial taxa were identified via MR analysis. Single-cell RNA sequencing and enrichment analyses elucidated underlying pathways, and drug predictions identified potential therapeutics.ResultsMR identified 19 bacterial taxa significantly associated with CRC. Protective effects were observed in taxa like RUG343 and Streptococcus_umgs_2425, while HOT-345_umgs_976 and W5053_sp000467935_mgs_712 increased CRC risk. Single-cell RNA sequencing revealed key pathways, including JAK-STAT signaling and tyrosine metabolism. Drug prediction highlighted potential therapeutics like Menadione Sodium Bisulfite and Raloxifene.ConclusionThis study establishes the critical role of the oral microbiome in colorectal cancer development, identifying specific microbial taxa linked to CRC risk. Single-cell RNA sequencing and drug prediction analyses further elucidate key pathways and potential therapeutics, providing novel insights and personalized treatment strategies for CRC.

Abstract BackgroundDrug users are a high-risk group for HIV infection and are prominent HIV carriers. Given the emergence of new drugs, we explored current drug-using behaviors, HIV infections, and the correlation between drug-using behaviors and HIV infection risk among drug users from 2014 to 2021. ObjectiveWe aimed to identify the prevalence of HIV infection risk among drug users and explore drug use behaviors based on the updated data, which could provide evidence for the precision of HIV prevention strategies among drug users. MethodsData were collected from sentinel surveillance of drug users in rehabilitation centers and communities in Hangzhou (2014‐2021), including sociodemographic characteristics, HIV awareness, drug use, risky sexual behaviors, and HIV infection status. Multivariate logistic regression was used to identify the factors influencing HIV infection and risky sexual behaviors among drug users. ResultsIn total, 5623 drug users (male: n=4734, 84.19%; age: mean 38.38, SD 9.94 years) were included. New drugs dominated among the participants (n=3674, 65.34%). The main mode of drug use was noninjection (n=4756, 84.58%). Overall, for 27.45% (n=1544) of injected drugs in the last month before the investigation, the average daily injection frequency was 3.10 (SD 8.24). Meanwhile, 3.43% of participants shared needles. The incidence of sexual behaviors after drug use was 33.13% (n=1863), with 35.75% (n=666) of them using a condom in the last time. Overall, 116 participants tested positive for HIV antibodies (infection rate=2.06%). New drug users exhibited more postuse sexual behaviors than traditional drug users (odds ratio [OR] 7.771, 95% CI 6.126‐9.856; PPPPPPP ConclusionsNew drug types and noninjection were the main patterns in last 7 years. Using new types of drugs, rather than traditional drugs, was associated with an increased risk of HIV infection. Injection drug use was a risk factor for HIV infection. HIV awareness among drug users was high, but the incidence of risky sexual behaviors remained high. Therefore, it is important to promote the behavioral transformation of high-risk populations from cognition to attitude, and then to taking protective measures.

Harmonics are an important cause of voltage distortion, and voltage reduction and voltage distortion are the main causes of commutation failure. But most of the current research studies on commutation failure are based on the drop in fundamental voltage after a fault, and there are few reports on the impact of voltage distortion on commutation failure. Aiming to solve the above problem, this article first analyzes the generation and transmission characteristics of harmonics in AC and DC systems, as well as the coupling degree of harmonics in DC systems. Then, starting from the mechanism of the commutation process, a commutation failure analysis method based on the harmonic voltage time area is proposed. This method can quantitatively analyze the impact of different harmonics on commutation failure. On this basis, the harmonic criteria for causing commutation failure are established, and the harmonic characteristics of AC voltage when harmonics cause subsequent commutation failure are quantitatively analyzed. Finally, a preventive controller is proposed to suppress commutation failure caused by different harmonics, where the above analysis is verified by the simulations.

BackgroundTryptophan Metabolism-associated Genes (TMGs), such as ECHS1 and ALDH2, are crucial in cancer progression through immunosuppressive mechanisms, particularly in Gastric Cancer (GC). This study explores their effects on the Tumor Microenvironment (TME). Additionally, it examines their potential as novel immunotherapy targets.MethodsWe utilized single-cell and bulk transcriptomic technologies to analyze the heterogeneity of GC. Non-negative Matrix Factorization (NMF) clustering identified key TMGs, and extensive RNA-seq analyses were performed to pinpoint prognostic genes and potential immunotherapy targets. Furthermore, through PCR analyses we found that ECHS1 and ALDH2 gene expression plays a regulatory role in the migration, invasion and inflammatory factor in AGS and SNU-1 cell lines. The interference effect of si-ECHS1 and ad-ALDH2 was validated using cell scratch assay in AGS and SNU-1 cell line.ResultsWe observed a statistically significant correlation between ECHS1 and ALDH2 expression and increased TME heterogeneity. Our findings also revealed that ECHS1 down-regulation and ALDH2 up-regulation contribute to reduced TME heterogeneity, decreased inflammation, and inhibited AGS and SNU-1 tumor cells migration and proliferation. GSVA enrichment analysis highlighted the NF-kappa B(NF-κB) signaling pathway as specifically regulated by TMGs. Furthermore,ECHS1 and ALDH2 modulated CD8+ and CD4+ T cell activities, impacting GC progression. In vitro experiments further solidified our conclusions by showcasing the inhibitory effects of Si-ECHS1 and ad-ALDH2 on the invasive and proliferative capabilities of AGS and SNU-1 cells. Moreover, Si-ECHS1 and ad-ALDH2 gene expression effectively reduced the expression of inflammatory factors IL-10,IL-7,CXCL8 and IL-6, leading to a remarkable alleviation of chronic inflammation and the heterogeneous nature of the TME.ConclusionThis research highlights the importance of ECHS1 and ALDH2 in GC progression and immune modulation, suggesting that targeted therapies focusing on these genes offer promising avenues for personalized immunotherapy in GC. These findings hold potential for improving patient survival and quality of life. Future studies on the NF-κB signaling pathway’s role in this context are warranted to further elucidate the mechanisms underlying TMG-mediated immune modulation in GC.

Nitrogen oxides (NOx) are common pollutants emitted from stationary sources, such as industrial boilers and power plants, with significant adverse impacts on the environment and biosphere. The abatement of NOx from anthropic industrial processes requires reliable and sensitive monitoring systems. To address this challenge, we report a sensitive, robust, and compact quantum cascade laser (QCL)-based sensor to measure NO and NO2 emissions from industrial exhausts. This sensor uses two quantum cascade lasers, which take advantage of the intense absorption spectra of NO at 1929 cm−1 and NO2 at 1599 cm−1. A high-temperature multipass cell is designed to withstand harsh environments, which increases the light path length. The NOx concentrations are directly determined from the wavelength modulation spectroscopic model without the need for calibration. We conducted several laboratory experiments to evaluate the sensor's performance, with a focus on accuracy, sensitivity and selectivity. In the end, we showcased the field deployment of our sensor by continuously measuring NOx concentrations in a 2.8-MW gas-fired industrial boiler.

Osteoblast-mediated bone formation and osteoclast-mediated bone resorption are critical processes in bone metabolism. Annexin A, a calcium–phospholipid binding protein, regulates the proliferation and differentiation of bone cells, including bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts, and has gradually become a marker gene for the diagnosis of osteoporosis. As calcium channel proteins, the annexin A family members are closely associated with mechanical stress, which can target annexins A1, A5, and A6 to promote bone cell differentiation. Despite the significant clinical potential of annexin A family members in bone metabolism, few studies have reported on these mechanisms. Therefore, based on a review of relevant literature, this article elaborates on the specific functions and possible mechanisms of annexin A family members in bone metabolism to provide new ideas for their application in the prevention and treatment of bone diseases, such as osteoporosis.

IntroductionThe microalga Chlorella sp. NeZha, recently isolated from a balcony environment, shows significant adaptability across various salinity conditions, including seawater (SeaW), freshwater (FreshW), and high salinity levels (45‰). This study investigates its potential for sustainable aquaculture and biotechnological applications.MethodsMorphological and genetic identification were conducted using optical microscopy and DNA sequencing. The microalga was cultivated in a 400 L outdoor photobioreactor, and its biochemical composition, including chlorophyll a, carbohydrate, protein, and lipid content, was analyzed. Its compatibility with zooplankton and growth in aquaculture wastewater were also evaluated.ResultsChlorella sp. NeZha produced chlorophyll a at concentrations exceeding seaweed and Spirulina by 10- and 5-fold, respectively, with a dry weight chlorophyll a content of 34.25 mg/g and 25 pg./cell. The microalga also contained carbohydrate (~33%), protein (~20%), and lipids (~14%). It was compatible with zooplankton species, such as rotifers and brine shrimp, and showed promising growth in aquaculture wastewater.DiscussionThe findings suggest that Chlorella sp. NeZha is a viable candidate for sustainable aquaculture and biotechnological applications, offering high nutritional value and environmental resilience. Its adaptability to diverse salinity conditions and ability to thrive in wastewater highlight its potential for bioremediation and use as feedstock for zooplankton. Further research is recommended to optimize its cultivation and explore broader applications.

Bone is a dynamically active tissue whose health status is closely related to its construction and remodeling, and imbalances in bone homeostasis lead to a wide range of bone diseases. The sulfated glycoprotein C-type lectin structural domain family 11 member A (Clec11a) is a key factor in bone mass regulation that significantly promotes the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts and stimulates chondrocyte proliferation, thereby promoting longitudinal bone growth. More importantly, Clec11a has high therapeutic potential for treating various bone diseases and can enhance the therapeutic effects of the parathyroid hormone against osteoporosis. Clec11a is also involved in the stress/adaptive response of bone to exercise via mechanical stimulation of the cation channel Pieoz1. Clec11a plays an important role in promoting bone health and preventing bone disease and may represent a new target and novel drug for bone disease treatment. Therefore, this review aims to explore the role and possible mechanisms of Clec11a in the skeletal system, evaluate its value as a potential therapeutic target against bone diseases, and provide new ideas and strategies for basic research on Clec11a and preventing and treating bone disease.

ObjectiveTo investigate the choice of treatment options and long-term orthopedic results of congenital kyphosis in children due to anterior vertebral bone bridges.MethodsThe clinical data of children with congenital kyphosis due to anterior vertebral bridges treated at our center from May 2005 to May 2020 were retrospectively analyzed. We evaluated the clinical features of the deformity, the choice of treatment plan, the change in the Cobb angle of the kyphosis and the improvement of the sagittal trunk deviation before and after treatment and at the final follow-up visit by means of pre-treatment and post-treatment imaging, physical examination and analysis of the case data.ResultsA total of 35 children were included. Clinical follow-up was conducted on a cohort of 5 children, all of whom presented with type Ⅱ congenital kyphosis caused by less than three thoracic anterior bone bridges. The study findings revealed no noteworthy advancement in segmental kyphosis, thoracic kyphosis, lumbar lordosis, and sagittal vertical axis during the final follow-up assessment (p > 0.05). In a cohort of 30 pediatric patients who underwent surgical intervention, segmental kyphosis was corrected, with a decrease from an average angle of (40.1 ± 20.5)° to (15.6 ± 9.5)°. Furthermore, significant improvements were noted in segmental kyphosis, thoracic kyphosis, lumbar lordosis, and sagittal vertical axis at the postoperative stage compared to the preoperative stage (p

Wire arc additive manufacturing (WAAM) is a metal 3D printing technique that allows large-scale elements to be built in a relatively timely and cost-effective manner, well suited to the cost-sensitive construction sector. Despite the potential of this novel technology, the basic properties of WAAM materials remain elusive. This paper presents a comparative study on the microstructure and corrosion behaviour of WAAM steel plates and the conventionally rolled Q345 steel. The WAAM steel exhibited comparable corrosion performance to the conventionally-produced steel within twelve days exposure in 3.5 wt% NaCl solution, including the corrosion current density, and the characteristics of steel/concrete interface, determined through electrochemical impedance spectroscopy (EIS) analysis. Post-corrosion observations revealed that preferential dissolution occurred at (Si, Mn)-rich oxide inclusions, in addition to the general corrosion of surrounding steel matrix. The much higher content of Si and Mn element in the feedstock material WAAM steel resulted in slightly higher susceptibility to localised corrosion, compared to the Q345 rolled steel.

Abstract Background Increasing attention is being paid to the environmental and health impacts of nanoplastics (NPs) pollution. Exposure to nanoplastics (NPs) with different charges and functional groups may have different adverse effects after ingestion by organisms, yet the potential ramifications on mammalian blood glucose levels, and the risk of diabetes remain unexplored. Results Mice were exposed to PS-NPs/COOH/NH2 at a dose of 5 mg/kg/day for nine weeks, either alone or in a T2DM model. The findings demonstrated that exposure to PS-NPs modified by different functional groups caused a notable rise in fasting blood glucose (FBG) levels, glucose intolerance, and insulin resistance in a mouse model of T2DM. Exposure to PS-NPs-NH2 alone can also lead the above effects to a certain degree. PS-NPs exposure could induce glycogen accumulation and hepatocellular edema, as well as injury to the pancreas. Comparing the effect of different functional groups or charges on T2DM, the PS-NPs-NH2 group exhibited the most significant FBG elevation, glycogen accumulation, and insulin resistance. The phosphorylation of AKT and FoxO1 was found to be inhibited by PS-NPs exposure. Treatment with SC79, the selective AKT activator was shown to effectively rescue this process and attenuate T2DM like lesions. Conclusions Exposure to PS-NPs with different functional groups (charges) induced T2DM-like lesions. Amino-modified PS-NPs cause more serious T2DM-like lesions than pristine PS-NPs or carboxyl functionalized PS-NPs. The underlying mechanisms involved the inhibition of P-AKT/P-FoxO1. This study highlights the potential risk of NPs pollution on T2DM, and provides a new perspective for evaluating the impact of plastics aging.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal tumor and has become an important global health problem. The PI3K/AKT signaling pathway plays a key role in the development of ESCC. CircRNAs have been reported to be involved in the regulation of the PI3K/AKT pathway, but the underlying mechanisms are unclear. Therefore, this study aimed to identify protein-coding circRNAs and investigate their functions in ESCC. Methods Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. Thereafter, LC–MS/MS was used to identify circPDE5A-encoded novel protein PDE5A-500aa. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circPDE5A and PDE5A-500aa in ESCC. Lastly, circRNA-loaded nanoplatforms were constructed to investigate the therapeutic translation value of circPDE5A. Results We found that circPDE5A expression was down-regulated in ESCC cells and tissues and that it was negatively associated with advanced clinicopathological stages and poorer prognosis in ESCC. Functionally, circPDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding PDE5A-500aa, a key regulator of the PI3K/AKT signaling pathway in ESCC. Mechanistically, PDE5A-500aa interacted with PIK3IP1 and promoted USP14-mediated de-ubiquitination of the k48-linked polyubiquitin chain at its K198 residue, thereby attenuating the PI3K/AKT pathway in ESCC. In addition, Meo-PEG-S–S-PLGA-based reduction-responsive nanoplatforms loaded with circPDE5A and PDE5A-500aa plasmids were found to successfully inhibit the growth and metastasis of ESCC in vitro and in vivo. Conclusion The novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of ESCC by promoting USP14-mediated de-ubiquitination of PIK3IP1 and may serve as a potential target for the development of therapeutic agents. Graphical Abstract The novel protein PDE5A-500aa encoded by circPDE5A can act as an inhibitor of the PI3K/AKT signaling pathway to inhibit the progression of esophageal squamous cell carcinoma.

Abstract Background This study aimed to systematically analyze the effect of a serine/threonine kinase (STK11) mutation (STK11mut) on therapeutic efficacy and prognosis in patients with non-small cell lung cancer (NSCLC). Methods Candidate articles were identified through a search of relevant literature published on or before April 1, 2023, in PubMed, Embase, Cochrane Library, CNKI and Wanfang databases. The extracted and analyzed data included the hazard ratios (HRs) of PFS and OS, the objective response rate (ORR) of immune checkpoint inhibitors (ICIs), and the positive rates of PD-L1 expression. The HR of PFS and OS and the merged ratios were calculated using a meta-analysis. The correlation between STK11mut and clinical characteristics was further analyzed in NSCLC datasets from public databases. Results Fourteen retrospective studies including 4317 patients with NSCLC of whom 605 had STK11mut were included. The meta-analysis revealed that the ORR of ICIs in patients with STK11mut was 10.1% (95%CI 0.9–25.2), and the positive rate of PD-L1 expression was 41.1% (95%CI 25.3–57.0). STK11mut was associated with poor PFS (HR = 1.49, 95%CI 1.28–1.74) and poor OS (HR = 1.44, 95%CI 1.24–1.67). In the bioinformatics analysis, PFS and OS in patients with STK11 alterations were worse than those in patients without alterations (p

Abstract Background Hepatocellular carcinoma (HCC) is widely recognized for its unfavorable prognosis. Increasing evidence has revealed that LGALS3 has an essential function in initiating and developing several malignancies in humans. Nevertheless, thorough analysis of the expression profile, clinical prognosis, pathway prediction, and immune infiltration of LGALS3 has not been fully explored in HCC. Methods In this study, an initial pan-cancer analysis was conducted to investigate the expression and prognosis of LGALS3. Following a comprehensive analysis, which included expression analysis and correlation analysis, noncoding RNAs that contribute to the overexpression of LGALS3 were subsequently identified. This identification was further validated using HCC clinical tissue samples. TIMER2 and GEPIA2 were employed to examine the correlation between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration in HCC. The R program was applied to analyze the expression distribution of immune score in in HCC patients with high and low LGALS3 expression. The expression profiles of immune checkpoints were also analyzed. Use R to perform GSVA analysis in order to explore potential signaling pathways. Results First, we conducted pan-cancer analysis for LGALS3 expression level through an in-depth analysis of public databases and found that HCC has a high LGALS3 gene and protein expression level, which were then verified in clinical HCC specimens. Meanwhile, high LGALS3 gene expression is related to malignant progression and poor prognosis of HCC. Univariate and multivariate analyses confirmed that LGALS3 could serve as an independent prognostic marker for HCC. Next, by combining comprehensive analysis and validation on HCC clinical tissue samples, we hypothesize that the HCP5/hsa-miR-27b-3p axis could serve as the most promising LGALS3 regulation mechanism in HCC. KEGG and GO analyses highlighted that the LGALS3-related genes were involved in tumor immunity. Furthermore, we detected a significant positive association between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration. In addition, high LGALS3 expression groups had significantly higher immune cell scores and immune checkpoint expression levels. Finally, GSVA analysis was performed to predict potential signaling pathways linked to LGALS3 and HCP5 in immune evasion and metabolic reprogramming of HCC. Conclusions Our findings indicated that the upregulation of LGALS3 via the HCP5/hsa-miR-27b-3p axis is associated with unfavorable prognosis and increased tumor immune infiltration in HCC.

Abstract Background Glycyrrhiza inflata Bat. and Glycyrrhiza uralensis Fisch. are both original plants of ‘Gan Cao’ in the Chinese Pharmacopoeia, and G. uralensis is currently the mainstream variety of licorice and has a long history of use in traditional Chinese medicine. Both of these species have shown some degree of tolerance to salinity, G. inflata exhibits higher salt tolerance than G. uralensis and can grow on saline meadow soils and crusty saline soils. However, the regulatory mechanism responsible for the differences in salt tolerance between different licorice species is unclear. Due to land area-related limitations, the excavation and cultivation of licorice varieties in saline-alkaline areas that both exhibit tolerance to salt and contain highly efficient active substances are needed. The systematic identification of the key genes and pathways associated with the differences in salt tolerance between these two licorice species will be beneficial for cultivating high-quality salt-tolerant licorice G. uralensis plant varieties and for the long-term development of the licorice industry. In this research, the differences in growth response indicators, ion accumulation, and transcription expression between the two licorice species were analyzed. Results This research included a comprehensive comparison of growth response indicators, including biomass, malondialdehyde (MDA) levels, and total flavonoids content, between two distinct licorice species and an analysis of their ion content and transcriptome expression. In contrast to the result found for G. uralensis, the salt treatment of G. inflata ensured the stable accumulation of biomass and total flavonoids at 0.5 d, 15 d, and 30 d and the restriction of Na+ to the roots while allowing for more K+ and Ca2+ accumulation. Notably, despite the increase in the Na+ concentration in the roots, the MDA concentration remained low. Transcriptome analysis revealed that the regulatory effects of growth and ion transport on the two licorice species were strongly correlated with the following pathways and relevant DEGs: the TCA cycle, the pentose phosphate pathway, and the photosynthetic carbon fixation pathway involved in carbon metabolism; Casparian strip formation (lignin oxidation and translocation, suberin formation) in response to Na+; K+ and Ca2+ translocation, organic solute synthesis (arginine, polyamines, GABA) in response to osmotic stresses; and the biosynthesis of the nonenzymatic antioxidants carotenoids and flavonoids in response to antioxidant stress. Furthermore, the differential expression of the DEGs related to ABA signaling in hormone transduction and the regulation of transcription factors such as the HSF and GRAS families may be associated with the remarkable salt tolerance of G. inflata. Conclusion Compared with G. uralensis, G. inflata exhibits greater salt tolerance, which is primarily attributable to factors related to carbon metabolism, endodermal barrier formation and development, K+ and Ca2+ transport, biosynthesis of carotenoids and flavonoids, and regulation of signal transduction pathways and salt-responsive transcription factors. The formation of the Casparian strip, especially the transport and oxidation of lignin precursors, is likely the primary reason for the markedly higher amount of Na+ in the roots of G. inflata than in those of G. uralensis. The tendency of G. inflata to maintain low MDA levels in its roots under such conditions is closely related to the biosynthesis of flavonoids and carotenoids and the maintenance of the osmotic balance in roots by the absorption of more K+ and Ca2+ to meet growth needs. These findings may provide new insights for developing and cultivating G. uralensis plant species selected for cultivation in saline environments or soils managed through agronomic practices that involve the use of water with a high salt content.

Abstract The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the organism. Among its various forms, skeletal interoception specifically regulates the metabolic homeostasis of bones. Osteoarthritis (OA) is a complex joint disorder involving cartilage, subchondral bone, and synovium. The subchondral bone undergoes continuous remodeling to adapt to dynamic joint loads. Recent findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone, resulting in subchondral bone sclerosis in OA. The skeletal interoception is also a potential mechanism for chronic synovial inflammation in OA. In this review, we offer a general overview of interoception, specifically skeletal interoception, subchondral bone microenviroment and the aberrant subchondral remedeling. We also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA, as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

Abstract The objective of this study is to develop and evaluate natural language processing (NLP) and machine learning models to predict infant feeding status from clinical notes in the Epic electronic health records system. The primary outcome was the classification of infant feeding status from clinical notes using Medical Subject Headings (MeSH) terms. Annotation of notes was completed using TeamTat to uniquely classify clinical notes according to infant feeding status. We trained 6 machine learning models to classify infant feeding status: logistic regression, random forest, XGBoost gradient descent, k-nearest neighbors, and support-vector classifier. Model comparison was evaluated based on overall accuracy, precision, recall, and F1 score. Our modeling corpus included an even number of clinical notes that was a balanced sample across each class. We manually reviewed 999 notes that represented 746 mother-infant dyads with a mean gestational age of 38.9 weeks and a mean maternal age of 26.6 years. The most frequent feeding status classification present for this study was exclusive breastfeeding [n = 183 (18.3%)], followed by exclusive formula bottle feeding [n = 146 (14.6%)], and exclusive feeding of expressed mother’s milk [n = 102 (10.2%)], with mixed feeding being the least frequent [n = 23 (2.3%)]. Our final analysis evaluated the classification of clinical notes as breast, formula/bottle, and missing. The machine learning models were trained on these three classes after performing balancing and down sampling. The XGBoost model outperformed all others by achieving an accuracy of 90.1%, a macro-averaged precision of 90.3%, a macro-averaged recall of 90.1%, and a macro-averaged F1 score of 90.1%. Our results demonstrate that natural language processing can be applied to clinical notes stored in the electronic health records to classify infant feeding status. Early identification of breastfeeding status using NLP on unstructured electronic health records data can be used to inform precision public health interventions focused on improving lactation support for postpartum patients.

Objective Natural fractures are important oil-gas migration channels and reservoir spaces in deep tight sandstone reservoirs and significantly affect oil-gas production capacity in the Bozi Block of the Kuqa Depression. Methods Based on rock core, thin slice, imaging log, and actual production data, the development characteristics of natural fractures in ultra-deep tight sandstone reservoirs in the Bozi Block, Kuqa Depression of Tarim Basin were clarified, and the effects of natural fractures on oil-gas production capacity were explored. Results Tectonic fractures developed in the ultra-deep reservoirs of the Bozi Block and were dominated by unfilled to semi-filled high-angle shear fractures accompanied by locally developed semi-filled to filled extensional fractures. Under the influence of multiphase tectonic movements, the natural fractures were mainly oriented N-S direction and NW-SE directionand partially oriented nearly E-W direction. Fractures are important reservoir spaces and seepage channels in the study area. Then, the fracture development coefficient and fracture validation coefficient were determined by using imaging log data and oil testing data, which were used to quantify the effects of fractures on oil and gas production. Quantitative evaluation plots between these two coefficients and gas-oil production were established. Validation showed that the fracture development coefficient and fracture validation coefficient can better evaluate the validity of fractures in the study area. Therefore, the classification and prediction of fracture-type reservoir quality based on fracture parameters were achieved. Conclusion This study not only provides a geological basis for efficient oil-gas exploration in the study area but also provides insight into how tight sandstone reservoir fractures affect oil-gas production.