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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.

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.

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.

To meet the use needs of LNG fuel tanks and storage tanks， the key process control of steel-making and rolling of 9Ni steel were carried， and the influence of two-phase area heat-treatment processes and Nb microalloying on micro⁃ structure and properties of 9Ni steel was studied. The results show that with the increase of intercritical quenching （IQ） temperature， the Yield stress（YS）， tensile strength （TS） and the ratio between YS and TS （Y/T） decreases firstly， then increases. Subsequently as the tempering temperature increases， the YS and TS gradually decrease， while the elongation increases； When the tempering temperature is 600 ℃， the YS and TS reach their lowest values， and the elongation （EL） reaches its peak. The microstructure after intercritical quenching presents distribution of large and small grains， which contributes to the reduction of Y/T ratio of steel plate. The microstructure of Nb micro-alloyed 9Ni low-temperature steel plate is mainly composed of tempered sorbite structure and 3% -8% reverse austenite. The addition of 0. 015% Nb in⁃ creases the average YS and TS of 9Ni low-temperature steel by about 50 MPa and 40 MPa， respectively. The impact ab⁃ sorption energy increases by about 40 J tested at -196 ℃.

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.

The emergence of stealth aircraft poses a challenge to the target detection capabilities of existing radar and infrared guided air-to-air missiles. Compared to the better radar stealth performance of stealth aircrafts, infrared guided air-to-air missiles have the advantage of anti stealth. However, some measures should be taken by the infrared seeker to improve its detection and recognition ability for stealth targets. In this paper, aiming to improve the ability of infrared imaging seeker to detect stealth targets, the infrared radiation characteristics of stealth aircraft are analyzed firstly. Then, based on the factors affecting the detection performance of infrared imaging seekers, various solution are proposed to improve the detection and recognition capabilities of infrared detection system for stealth aircraft, such as using dual color/multi band imaging detection, optimizing the working parameter design of infrared detection system, increasing imaging quality and scene adaptability in different environments, and adopting low signal-to-clutter ratio target detection and interception technology.

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.

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.