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Abstract Purpose This research evaluates the effect of balloon pulmonary angioplasty (BPA) on cardiac electrophysiological changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods Involving a retrospective analysis of 39 CTEPH patients (average age 61 ± 11), who had at least two BPAs and paired ECGs pre- and post-surgery, we examined changes in ECG indicators of right ventricular hypertrophy and their correlation with hemodynamic results. Results BPA yielded marked improvements in cardiac function and hemodynamics. ECG parameters, specifically the Lewis criteria and Butler-Leggett score, correlated strongly with hemodynamics and were predictive of a mean pulmonary arterial pressure (mPAP) ≥ 35mmHg. Notably, QRS complex axis normalization was observed in 25 patients, with 14 fully normalizing (range − 30° to + 90°). The qR pattern in V1 vanished in 9 cases, and 75% of the patients in qR pattern in V1 group had QRS complex electrical axis completely returned to normal range. The qR V1 group had higher mPAP and pulmonary vascular resistance (PVR), and lower cardiac output and index compared to the non-qR V1 group, alongside a higher Butler-Leggett score. Conclusions BPA enhances cardiac function and hemodynamics in CTEPH patients, with certain ECG measures such as Lewis criteria and Butler-Leggett score reflecting the severity of hemodynamic impairment. The reversal of QRS axis deviation and the disappearance of the qR pattern in lead V1 may serve as valuable indicators for assessing post-BPA satisfaction in CTEPH patients.

Abstract To enhance the drilling efficiency and extend the service life of PDC (Polycrystalline Diamond Composite) bits in shale formations, this study delves into the rock-breaking mechanisms of special-shaped cutters through a comprehensive experimental approach. This involves optimizing the cutter designs, conducting laboratory experiment and field testing. Among the various cutter geometries considered, concave, axe, planar, and triangular cutters are chosen as the focal points for unit rock-breaking experiments. These tests aim to assess their cutting loads and cutting specific energy to gain a deeper understanding of their performance characteristics. Based on experimental, the debris characteristics are analyzed. Based on the understanding of the shale-breaking characteristics of special-shaped cutters, field testing is performed using a novel PDC bit with a special-shaped cutter. Compared with planar cutters, the concave cutter and the triangular cutter generate lower cutting loads and cutting specific energy. Under identical conditions, the average cutting force and cutting specific energy of concave cutter at different cutting depths are reduced by 16.1% and 19.6% Specifically, the concave cutter generates the largest debris when operated under similar conditions, which is beneficial for increasing rock-breaking efficiency. Laboratory experiment indicate that compared to conventional drill bits, the novel drill bit experiences an increase in torque of approximately 9.8% with increasing WOB (weight on bit). Under high WOB, the ROP (rate of penetration) increases by about 75.4%, while the mechanical specific energy decreases by nearly 40%. Additionally, the novel bit vibration characteristics remain superior to conventional drill bits. Field testing shows that the average ROP of the novel bit and total footage drilled increase by up to 13.3% and 27.2%, respectively, in comparison with those for the conventional bit. The research results are helpful to speed up the efficiency of shale gas drilling.

Abstract Lipotoxicity is a well-established phenomenon that could exacerbate damage to islet β-cells and play a significant role in the development of type 2 diabetes, the underlying mechanisms of which, however, remain unclear. In lipotoxic conditions, secretagogin (SCGN), an EF-hand calcium-binding protein abundantly expressed in islets, is found to undergo downregulation. In light of this, we aim to explore the role of SCGN in lipotoxicity-induced β-cell injury. Our findings show that exposure to ox-LDL in vitro or long-term high-fat diets (HFD) in vivo decreases SCGN expression and induces pyroptosis in β-cells. Moreover, restoring SCGN partially reverses the pyroptotic cell death under ox-LDL or HFD treatments. We have observed that the downregulation of SCGN facilitates the translocation of ChREBP from the cytosol to the nucleus, thereby promoting TXNIP transcription. The upregulation of TXNIP activates the NLRP3/Caspase-1 pathway, leading to pyroptotic cell death. In summary, our study demonstrates that lipotoxicity leads to the downregulation of SCGN expression in islet β-cells, resulting in ChREBP accumulation in the nucleus and subsequent activation of the NLRP3/Caspase-1 pyroptotic pathway. Thus, administering SCGN could be a potential therapeutic strategy to alleviate β-cell damage induced by lipotoxicity in type 2 diabetes.

Abstract Picolitre monodisperse droplet printing technology has important applications in biochemistry, such as accounting for quantitative analysis and single-cell analysis, and can be used for parallel high-throughput analysis of biomarkers and chemicals. However, commonly used droplet generation devices require complex control systems or customised microfluidic chips, making them costly and difficult for researchers to operate. Additionally, generating picolitre monodisperse droplets with microfluidic devices necessitates the introduction of an oil phase to block and separate the liquid. This requirement can reduce the throughput of the target droplets and cause cell contamination, hindering the adoption of this technology. By employing a common 1-mm-diameter capillary in the laboratory in combination with a piezoelectric transducer, we have achieved on-demand picolitre droplet printing of less than 100 pL in an oil-free environment. The device was found to be biocompatible with K562 cells. This approach is less costly, offers greater operational freedom, and is easier to integrate with other downstream assay modules or even handheld cell-printing devices. This study holds great potential for application in areas such as single-cell analysis, cell sampling, and pharmaceutical analysis.

Abstract Background For women who have experienced recurrent pregnancy loss (RPL), it is crucial not only to treat them but also to evaluate the risk of recurrence. The study aimed to develop a risk predictive model to predict the subsequent early pregnancy loss (EPL) in women with RPL based on preconception data. Methods A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to December 2022, a total of 1050 non-pregnant women with RPL were participated. By December 2023, 605 women had subsequent pregnancy outcomes and were randomly divided into training and validation group by 3:1 ratio. In the training group, univariable screening was performed on RPL patients with subsequent EPL outcome. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables, respectively. Subsequent EPL prediction model was constructed using generalize linear model (GLM), gradient boosting machine (GBM), random forest (RF), and deep learning (DP). The variables selected by LASSO regression and multivariate logistic regression were then established and compared using the best prediction model. The AUC, calibration curve, and decision curve (DCA) were performed to assess the prediction performances of the best model. The best model was validated using the validation group. Finally, a nomogram was established based on the best predictive features. Results In the training group, the GBM model achieved the best performance with the highest AUC (0.805). The AUC between the variables screened by the LASSO regression (16-variables) and logistic regression (9-variables) models showed no significant difference (AUC: 0.805 vs. 0.777, P = 0.1498). Meanwhile, the 9-variable model displayed a well discrimination performance in the validation group, with an AUC value of 0.781 (95%CI 0.702, 0.843). The DCA showed the model performed well and was feasible for making beneficial clinical decisions. Calibration curves revealed the goodness of fit between the predicted values by the model and the actual values, the Hosmer–Lemeshow test was 7.427, and P = 0.505. Conclusions Predicting subsequent EPL in RPL patients using the GBM model has important clinical implications. Future prospective studies are needed to verify the clinical applicability. Trial registration This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

Sclerostin emerges as a novel target for bone anabolic therapy in bone diseases. Osteogenesis imperfecta (OI) and X-linked hypophosphatemia (XLH) are rare bone diseases in which therapeutic potential of sclerostin inhibition cannot be ignored. In OI, genetic/pharmacologic sclerostin inhibition promoted bone formation of mice, but responses varied by genotype and age. Serum sclerostin levels were higher in young OI-I patients, while lower in adult OI-I/III/IV. It's worth investigating whether therapeutic response of OI to sclerostin inhibition could be clinically predicted by genotype and age. In XLH, preclinical/clinical data suggested factors other than identified FGF23 contributing to XLH. Higher levels of circulating sclerostin were detected in XLH. Sclerostin inhibition promoted bone formation in Hyp mice, while restored phosphate homeostasis in age-/gender-dependent manner. The role of sclerostin in regulating phosphate metabolism deserves investigation. Sclerostin/FGF23 levels of XLH patients with/without response to FGF23-antibody warrants study to develop precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy. Notably, OI patients were associated with cardiovascular abnormalities, so were XLH patients receiving conventional therapy. Targeting sclerostin loop3 promoted bone formation without cardiovascular risks. Further, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.The Translational Potential of this Article.Preclinical data on the molecular understanding of sclerostin inhibition in OI and therapeutic efficacy in mouse models of different genotypes, as well as clinical data on serum sclerostin levels in patients with different phenotypes of OI, were reviewed and discussed. Translationally, it would facilitate to develop clinical prediction strategies (e.g. based on genotype and age, not just phenotype) for OI patients responsive to sclerostin inhibition. Both preclinical and clinical data suggested sclerostin as another factor contributing to XLH, in addition to the identified FGF23. The molecular understanding and therapeutic effects of sclerostin inhibition on both promoting bone anabolism and improving phosphate homostasis in Hyp mice were reviewed and discussed. Translationaly, it would facilitate the development of precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy for the treatment of XLH. Cardiovascular risk could not be ruled out during sclerostin inhibition treatment, especially for OI and XLH patients with cardiovascular diseases history and cardiovascular abnormalities. Studies on the role of sclerostin in inhiting bone formation and protecting cardiovascular system were reviewed and discussed. Translationaly, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.

In recent years, rapid city development has significantly impacted the microclimate environments in urban blocks. Many studies have shown that varied built-up environmental factors lead to corresponding degrees of influence on microclimate. Urban blocks are one of the most concentrated urban settlements, and their impact on the urban climate and environment cannot be ignored. Taking the Fengtai district in Beijing as an example, using the ArcGIS platform inputted with meteorological data and built-up environment data, this study selected climate-sensitive units in the Fengtai district, of which 746 highly sensitive block units were obtained. SPSS software was used to analyze the correlation between built-up environmental factors and climate elements, and the relationship between the degree of influence and magnitude was analyzed using a regression equation. An optimization strategy for built-up environments on an urban block scale was proposed. A model for improving the climate environment at the urban block scale is summarized. Coupling study between climate environment and influencing factors at the urban block scale is an effective way to deal with the improvement of the urban microclimate environment and refinement transformation in the post-epidemic era.

Abstract This study compares postoperative visual outcomes and optical aberrations after Small Incision Lenticule Extraction (SMILE) in patients with both small (S-Kappa: Kappa angle

Abstract Background Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored. Methods The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk. Results MTF1 rs28411034 (OR 1.22, 95% CI 1.03–1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04–1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p

Abstract Efficiently converting solar energy into chemical energy remains a formidable challenge in artificial photosynthetic systems. To date, rarely has an artificial photosynthetic system operating in the open air surpassed the highest solar-to-biomass conversion efficiency (1%) observed in plants. In this study, we present a three-dimension polymeric photocatalyst achieving a solar-to-H2O2 conversion efficiency of 3.6% under ambient conditions, including real water, open air, and room temperature. The impressive performance is attributed to the efficient storage of electrons inside materials via expeditious intramolecular charge transfer, and the fast extraction of the stored electrons by O2 that can diffuse into the internal pores of the self-supporting three-dimensional material. This construction strategy suppresses the interlayer transfer of excitons, polarizers and carriers, effectively increases the utilization of internal excitons to 82%. This breakthrough provides a perspective to substantially enhance photocatalytic performance and bear substantial implications for sustainable energy generation and environmental remediation.

Abstract With the widespread application of composite insulators in transmission lines, exploring the accumulation mechanism of pollution particles on composite insulator surfaces is of importance to ensure the safe and steady operation of the power system. Addressing the current theoretical shortcomings, this study categorises the accumulation process of particles on the insulator surface into three stages, namely ‘spatial motion’, ‘surface collision’, and ‘surface motion’. The motion and rotation velocities in a multi‐physics field are calculated in the spatial motion stage. In the surface collision stage, a parameter called ‘neck height’ is introduced to determine the optimum mechanics theory, and the normal deposition criterion is established. For the surface motion stage, the sliding displacement and rolling displacement on the surface are calculated based on the rotation speed of the particles. A dynamic pollution accumulation model of the composite insulator is established based on the normal deposition criterion and tangential displacement. Finally, numerical simulations are performed by using the finite element method. Simulation results show that the proposed model agrees with the actual insulator pollution accumulation, and the deposition model is still applicable for various types of composite insulators operating in different applied voltages. The deposition probability of particles increases with the increasing particle size. In the surface motion stage, particle displacement increases with particle size and wind velocity.

Abstract As urban areas expand globally, human activities are leading to a sustained increase in non-methane volatile organic compound (NMVOC) emissions, escalating both environmental and health-related concerns. Given their diverse origins, estimating anthropogenic NMVOC emissions levels from global urban areas remains challenging. Here, we integrate TROPOspheric Monitoring Instrument (TROPOMI) formaldehyde (HCHO) column data, Visible Infrared Imaging Radiometer Suite (VIIRS) nighttime light (NTL) radiance data, and the Emission Database for Global Atmospheric Research (EDGAR) to develop a method for estimating global anthropogenic NMVOC emissions. Furthermore, we construct a linear model to analyze the relationship between urbanization and anthropogenic NMVOC emissions. Our research reveals that meticulously filtered TROPOMI HCHO columns have a high Pearson correlation coefficient (r = 0.91) with anthropogenic NMVOC emissions, indicating its reliability as an indicator reflecting the levels of anthropogenic NMVOC emissions. We establish linear models at various scales, including global, continental, and national, linking HCHO columns (as indicators of anthropogenic NMVOC emissions) and NTL radiance (as an indicator of urbanization). The global-scale linear model exhibits an r of 0.81, with a slope of 0.42 × 1015 molec. cm−2 nanoWatts−1 cm2 sr and an intercept of 9.26 × 1015 molec. cm−2. This linear model reflects a positive correlation between urbanization and anthropogenic NMVOC emissions, also serving as a tool for estimating the levels of anthropogenic NMVOC emissions in urban areas. This study offers valuable insights for real-time monitoring of extensive anthropogenic NMVOC emissions.

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt4+ with modified g-C3N4 by π–π interaction to prepare g–C3N4–loaded Pt single-atom (Pt SA/C3N4) nanozymes that serve as superoxide dismutase (SOD)/catalase (CAT) mimics to scavenge ROS/RNS and regulate mitochondrial ATP production, ultimately delaying the progression of OA. Pt SA/C3N4 exhibited a high loading of Pt single atoms (2.45 wt%), with an excellent photothermal conversion efficiency (54.71%), resulting in tunable catalytic activities under near-infrared light (NIR) irradiation. Interestingly, the Pt–N6 active centres in Pt SA/C3N4 formed electron capture sites for electron holes, in which g-C3N4 regulated the d-band centre of Pt, and the N-rich sites transferred electrons to Pt, leading to the enhanced adsorption of free radicals and thus higher SOD- and CAT-like activities compared with pure g-C3N4 and g–C3N4–loaded Pt nanoparticles (Pt NPs/C3N4). Based on the use of H2O2-induced chondrocytes to simulate ROS-injured cartilage in vitro and an OA joint model in vivo, the results showed that Pt SA/C3N4 could reduce oxidative stress-induced damage, protect mitochondrial function, inhibit inflammation progression, and rebuild the OA microenvironment, thereby delaying the progression of OA. In particular, under NIR light irradiation, Pt SA/C3N4 could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C3N4 regulated the expression of mitochondrial respiratory chain complexes, mainly NDUFV2 of complex 1 and MT-ATP6 of ATP synthase, to reduce ROS/RNS and promote ATP production. This study provides novel insights into the design of artificial nanozymes for treating oxidative stress-induced inflammatory diseases.

Abstract Breast cancer risks in older BRCA2 pathogenic variant carriers are understudied. Recent studies show a marked decline in the relative risk at older ages. We used data from two large studies to update the breast cancer risks in the BOADICEA model for BRCA2 carriers 60 years and older.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Abstract Porous materials with ultrahigh specific strength are highly desirable for aerospace, automotive and construction applications. However, because of the harsh processing of metal foams and intrinsic low strength of polymer foams, both are difficult to meet the demand for scalable development of structural foams. Herein, we present a supramolecular metallic foam (SMF) enabled by core-shell nanostructured liquid metals connected with high-density metal-ligand coordination and hydrogen bonding interactions, which maintain fluid to avoid stress concentration during foam processing at subzero temperatures. The resulted SMFs exhibit ultrahigh specific strength of 489.68 kN m kg−1 (about 5 times and 56 times higher than aluminum foams and polyurethane foams) and specific modulus of 281.23 kN m kg−1 to withstand the repeated loading of a car, overturning the previous understanding of the difficulty to achieve ultrahigh mechanical properties in traditional polymeric or organic foams. More importantly, end-of-life SMFs can be reprocessed into value-added products (e.g., fibers and films) by facile water reprocessing due to the high-density interfacial supramolecular bonding. We envisage this work will not only pave the way for porous structural materials design but also show the sustainable solution to plastic environmental risks.

Abstract Narrow bandwidths are a general bottleneck for applications relying on passive, linear, subwavelength resonators. In the past decades, several efforts have been devoted to overcoming this challenge, broadening the bandwidth of small resonators by the means of analog non-Foster matching networks for radiators, antennas and metamaterials. However, most non-Foster approaches present challenges in terms of tunability, stability and power limitations. Here, by tuning a subwavelength acoustic transducer with digital non-Foster-inspired electronics, we demonstrate five-fold bandwidth enhancement compared to conventional analog non-Foster matching. Long-distance transmission over airborne acoustic channels, with approximately three orders of magnitude increase in power level, validates the performance of the proposed approach. We also demonstrate convenient reconfigurability of our non-Foster-inspired electronics. This implementation provides a viable solution to enhance the bandwidth of sub-wavelength resonance-based systems, extendable to the electromagnetic domain, and enables the practical implementation of airborne and underwater acoustic radiators.

Abstract Toll-like receptor 9 (TLR9) recognizes bacterial, viral and self DNA and play an important role in immunity and inflammation. However, the role of TLR9 in obesity is less well-studied. Here, we generate B-cell-specific Tlr9-deficient (Tlr9 fl/fl /Cd19Cre +/- , KO) B6 mice and model obesity using a high-fat diet. Compared with control mice, B-cell-specific-Tlr9-deficient mice exhibited increased fat tissue inflammation, weight gain, and impaired glucose and insulin tolerance. Furthermore, the frequencies of IL-10-producing-B cells and marginal zone B cells were reduced, and those of follicular and germinal center B cells were increased. This was associated with increased frequencies of IFNγ-producing-T cells and increased follicular helper cells. In addition, gut microbiota from the KO mice induced a pro-inflammatory state leading to immunological and metabolic dysregulation when transferred to germ-free mice. Using 16 S rRNA gene sequencing, we identify altered gut microbial communities including reduced Lachnospiraceae, which may play a role in altered metabolism in KO mice. We identify an important network involving Tlr9, Irf4 and Il-10 interconnecting metabolic homeostasis, with the function of B and T cells, and gut microbiota in obesity.

The unique combination of lightweight, strength, corrosion resistance, high-temperature resistance, and biocompatibility make Ti6Al4V alloy an important material in metal contact of solar cells, and selective laser melting (SLM) enables the production of Ti6Al4V parts complex geometries that would be difficult or impossible to produce using traditional manufacturing methods. The build orientation of SLM process presents an essential effect on the quality of the produced parts, and thus, in this study it investigates the impact of multi-build orientation (0°, 30°, 45°, 60°, 90°) on the microstructural evolution and mechanical behavior of truly as-built Ti6Al4V alloys produced by SLM. The microstructure analysis revealed the presence of ordered subsurface pores, located at a distance of about 50 μm–150 μm from the sample surface. The microstructure consisted primarily of α′ martensite with a small amount of β phase. Massive transformation was observed in the 30° and 45° samples, with corresponding grain sizes of 5 μm and 10 μm, respectively. To be specific, the content of β phase and ultimate tensile strength (UTS) varied with the sample orientation, and the 45° build orientation exhibited the highest content of β phase with value of approximately 2.8%, but also the lowest UTS and elongation, which were 1161 MPa and 3.99%, respectively.

The origin and acceleration of solar and heliospheric energetic particles have been prevalent research frontiers in space physics. Solar and heliospheric energetic particles measured in the interplanetary medium (IPM) can be classified into two major groups: continuous "solar wind suprathermal particles" and transient "solar energetic particles". Due to the limited sensitivity of instruments used to investigate energetic particles in the IPM, the origin/acceleration processes of heliospheric energetic particles remain poorly understood. In this study, we designed a new-generation interplanetary ultralow-noise three-dimensional energetic particle spectrometer meeting leading world-class specifications. The spectrometer utilizes a double-ended telescope structure and multi-layer, multi-pixel semiconductor detectors to assess the complete three-dimensional distribution of 20-1000 keV electrons and 25-12000 keV protons in the IPM. The spectrometer integrates the following cutting-edge technologies: (1) utilizing anti-coincidence correlations between adjacent detectors with narrow interlayer spacing to minimize the noise generated by cosmic rays and other high-energy penetrating particles in the semiconductor detectors; (2) a double-ended open telescope structure design, with thin foil covering to stop protons for high-sensitivity electron detection in one direction, magnets to sweep away electrons for high-sensitivity proton detection in the opposite direction, multi-layer detectors for dE/dX analysis, and high-precision discrimination of electron, proton, and helium ion types; (3) a large-area silicon semiconductor detector, combined with a large field of view covering nearly 4π solid angles, to improve the geometric factor and temporal resolution of the spectrometer; (4) four layers of a 5-pixel silicon semiconductor detector array to achieve high angular resolution; and (5) low-noise multi-channel Application Specific Integrated Circuit (ASIC) technology to achieve precise energy level observation and high energy resolution. The spectrometer will provide key measurements that reveal the physical nature of the origin/acceleration processes of solar and heliospheric energetic particles, which will prove beneficial for the upcoming interplanetary and deep space explorations by China.

Objective(s): Luteolin is a flavone that provides defense against myocardial ischemia/reperfusion (I/R) injury. However, this compound is subjected to methylation mediated by catechol-O-methyltransferase (COMT), thus influencing its pharmacological effect. To synthesize a new flavone from luteolin that avoids COMT-catalyzed methylation and find out the protective mechanism of LUA in myocardial I/R injury.Materials and Methods: Luteolin and 2,2’-azobis (2-amidinopropane) dihydrochloride (AAPH) were used to synthesize the new flavone known as LUAAPH-1 (LUA). Then, the myocardial ischemia/reperfusion injury cell model was established using H9c2 cells to detect the effect in myocardial ischemia/reperfusion regulation and to identify the underlying mechanism. Results: Pretreatment with LUA (20 μmol/l) substantially increased cell viability while reducing cell apoptosis rate and caspase-3 expression induced by I/R, and the protective effect of LUA on cell viability was stronger than diosmetin, which is the major methylated metabolite of luteolin. In addition, intracellular reactive oxygen species (ROS) production and calcium accumulation were both inhibited by LUA. Furthermore, we identified that LUA markedly relieved the promotive effects of I/R stimulation upon JNK and p38 phosphorylation.Conclusion: LUT pretreatment conveys significant cardioprotective effects after myocardial I/R injury, and JNK and p38 MAPK signaling pathway may be involved.

Abstract With recent advancements in robotic surgery, notable strides have been made in visual question answering (VQA). Existing VQA systems typically generate textual answers to questions but fail to indicate the location of the relevant content within the image. This limitation restricts the interpretative capacity of the VQA models and their ability to explore specific image regions. To address this issue, this study proposes a grounded VQA model for robotic surgery, capable of localizing a specific region during answer prediction. Drawing inspiration from prompt learning in language models, a dual-modality prompt model was developed to enhance precise multimodal information interactions. Specifically, two complementary prompters were introduced to effectively integrate visual and textual prompts into the encoding process of the model. A visual complementary prompter merges visual prompt knowledge with visual information features to guide accurate localization. The textual complementary prompter aligns visual information with textual prompt knowledge and textual information, guiding textual information towards a more accurate inference of the answer. Additionally, a multiple iterative fusion strategy was adopted for comprehensive answer reasoning, to ensure high-quality generation of textual and grounded answers. The experimental results validate the effectiveness of the model, demonstrating its superiority over existing methods on the EndoVis-18 and EndoVis-17 datasets.

Abstract This study aimed to develop and validate a nomogram model that includes clinical and laboratory indicators to predict the risk of metabolic-associated fatty liver disease (MAFLD) in young Chinese individuals. This study retrospectively analyzed a cohort of young population who underwent health examination from November 2018 to December 2021 at The Affiliated Hospital of Southwest Medical University in Luzhou City, Sichuan Province, China. We extracted the clinical and laboratory data of 43,040 subjects and randomized participants into the training and validation groups (7:3). Univariate logistic regression analysis, the least absolute shrinkage and selection operator regression, and multivariate logistic regression models identified significant variables independently associated with MAFLD. The predictive accuracy of the model was analyzed in the training and validation sets using area under the receiver operating characteristic (AUROC), calibration curves, and decision curve analysis. In this study, we identified nine predictors from 31 variables, including age, gender, body mass index, waist-to-hip ratio, alanine aminotransferase, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uric acid, and smoking. The AUROC for the subjects in the training and validation groups was 0.874 and 0.875, respectively. The calibration curves show excellent accuracy of the nomogram. This nomogram which was based on demographic characteristics, lifestyle habits, anthropometrics, and laboratory data can visually and individually predict the risk of developing MAFLD. This nomogram is a quick and effective screening tool for assessing the risk of MAFLD in younger populations and identifying individuals at high risk of MAFLD, thereby contributing to the improvement of MAFLD management.

Abstract Background The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. Methods Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. Results The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. Conclusion Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. Simple summary The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.

Abstract Non-small cell lung cancer (NSCLC) is a prevalent form of lung cancer. Patients with advanced NSCLC are currently being treated with various therapies, including traditional radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. However, a considerable proportion of advance patients who cannot benefit from them. Consequently, it is essential to identify a novel research target that offers an encouraging perspective. The stimulator of interferon genes (STING) has emerged as such a target. At present, it is confirmed that activating STING in NSCLC tumor cells can impede the proliferation and metastasis of dormant tumor cells. This review focuses on the role of STING in NSCLC treatment and the factors influencing its activation. Additionally, it explores the correlation between STING activation and diverse therapy modalities for NSCLC, such as radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. Furthermore, it proposes the prospect of innovative therapy methods involving nanoparticles, with the aim of using the features of STING to develop more strategies for NSCLC therapy.

The Sb3+ doping strategy has been proven to be an effective way to regulate the band gap and improve the photophysical properties of organic-inorganic hybrid metal halides (OIHMHs). However, the emission of Sb3+ ions in OIHMHs is primarily confined to the low energy region, resulting in yellow or red emissions. To date, there are few reports about green emission of Sb3+-doped OIHMHs. Here, we present a novel approach for regulating the luminescence of Sb3+ ions in 0D C10H22N6InCl7·H2O via hydrogen bond network, in which water molecules act as agents for hydrogen bonding. Sb3+-doped C10H22N6InCl7·H2O shows a broadband green emission peaking at 540 nm and a high photoluminescence quantum yield (PLQY) of 80%. It is found that the intense green emission stems from the radiative recombination of the self-trapped excitons (STEs). Upon removal of water molecules with heat, C10H22N6In1-xSbxCl7 generates yellow emission, attributed to the breaking of the hydrogen bond network and large structural distortions of excited state. Once water molecules are adsorbed by C10H22N6In1-xSbxCl7, it can subsequently emit green light. This water-induced reversible emission switching is successfully used for optical security and information encryption. Our findings expand the understanding of how the local coordination structure influences the photophysical mechanism in Sb3+-doped metal halides and provide a novel method to control the STEs emission.

Abstract Background At present, individualized interventions can be given to patients with a clear etiology of pregnancy loss to improve the subsequent pregnancy outcomes, but the current reproductive status of the patient cannot be changed. The aim of this study was to investigate the association between female reproductive status and subsequence pregnancy outcome in patients with prior pregnancy loss (PL). Methods A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to February 2022, a total of 1955 women with at least one previous PL were enrolled. Maternal reproductive status and subsequent reproductive outcomes were recorded through an electronic medical record system and follow-up. Logistic regression was used to evaluate the association between reproductive status and the risk of subsequent reproductive outcomes. Results Among all patients, the rates of subsequent infertility, early PL, late PL, and live birth were 20.82%, 24.33%, 1.69% and 50.77% respectively. In logistic regression, we found that age (OR 1.08, 95% CI 1.04–1.13) and previous cesarean delivery history (OR 2.46, 95% CI 1.27–4.76) were risk factors for subsequent infertility in patients with PL. Age (OR 1.06, 95% CI 1.03–1.10), age at first pregnancy (OR 1.06, 95% CI 1.03–1.10), BMI (OR 1.06, 95% CI 1.02–1.11), previous PL numbers (OR 1.18, 95% CI 1.04–1.57) and without pre-pregnancy intervention (OR 1.77, 95% CI 1.35–2.24) were risk factors for non-live birth. Age (OR 1.06, 95% CI 1.03–1.09), age at first pregnancy (OR 1.06, 95% CI 1.02–1.09), BMI (OR 1.07, 95% CI 1.02–1.11), previous PL numbers (OR 1.15, 95% CI 1.02–1.31) and without pre-pregnancy intervention (OR 2.16, 95% CI 1.65–2.84) were risk factors for PL. Conclusions The reproductive status of people with PL is strongly correlated with the outcome of subsequent pregnancies. Active pre-pregnancy intervention can improve the subsequent pregnancy outcome. Trial registration This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

Abstract YEATS domain-containing protein GAS41 is a histone reader and oncogene. Here, through genome-wide CRISPR-Cas9 screenings, we identify GAS41 as a repressor of ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recognizing the H3K27-acetylation (H3K27-ac) marker, GAS41 is recruited to the SLC7A11 promoter, independent of NRF2 binding. By bridging the interaction between NRF2 and the H3K27-ac marker, GAS41 acts as an anchor for NRF2 on chromatin in a promoter-specific manner for transcriptional activation. Moreover, the GAS41-mediated effect on ferroptosis contributes to its oncogenic role in vivo. These data demonstrate that GAS41 is a target for modulating tumor growth through ferroptosis. Our study reveals a mechanism for GAS41-mediated regulation in transcription by anchoring NRF2 on chromatin, and provides a model in which the DNA binding activity on chromatin by transcriptional factors (NRF2) can be directly regulated by histone markers (H3K27-ac).

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is more widespread in animals than previously thought, and it may be able to infect a wider range of domestic and wild species. To effectively control the spread of the virus and protect animal health, it is crucial to understand the cross-species transmission mechanisms and risk factors of SARS-CoV-2. This article collects published literature on SARS-CoV-2 in animals and examines the distribution, transmission routes, biophysical, and anthropogenic drivers of infected animals. The reported cases of infection in animals are mainly concentrated in South America, North America, and Europe, and species affected include lions, white-tailed deer, pangolins, minks, and cats. Biophysical factors influencing infection of animals with SARS-CoV-2 include environmental determinants, high-risk landscapes, air quality, and susceptibility of different animal species, while anthropogenic factors comprise human behavior, intensive livestock farming, animal markets, and land management. Due to current research gaps and surveillance capacity shortcomings, future mitigation strategies need to be designed from a One Health perspective, with research focused on key regions with significant data gaps in Asia and Africa to understand the drivers, pathways, and spatiotemporal dynamics of interspecies transmission.

Abstract Brain perfusion and blood-brain barrier (BBB) integrity are reduced early in Alzheimer’s disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD and non-diseased control brains to characterise pathological transcriptional signatures responsible for this. We show that endothelial cells (EC) are enriched for expression of genes associated with susceptibility to AD. Increased β-amyloid is associated with BBB impairment and a dysfunctional angiogenic response related to a failure of increased pro-angiogenic HIF1A to increased VEGFA signalling to EC. This is associated with vascular inflammatory activation, EC senescence and apoptosis. Our genomic dissection of vascular cell risk gene enrichment provides evidence for a role of EC pathology in AD and suggests that reducing vascular inflammatory activation and restoring effective angiogenesis could reduce vascular dysfunction contributing to the genesis or progression of early AD.

Abstract Background The impact of vitamin D on type 1 diabetes has been a controversial topic in public health. Furthermore, significant differences in the proportion of vitamin D have been noted. The purpose of this systematic review was to determine the overall proportion of vitamin D deficiency in children/adolescents with type 1 diabetes (T1D). Methods Based on six electronic databases (PubMed, Web of Science, Embase, Ovid Medline, ProQuest, and Cochrane Library), eligible studies since the databases’ inception up to April 2022 were searched. Reference lists were also manually searched to identify additional studies. Overall, studies with statistical information on vitamin D deficiency in children and adolescents with T1D were included, and a random effects model was applied for the meta-analysis. In addition, subgroup and sensitivity analyses were carried out to evaluate heterogeneity, and publication bias was evaluated by using Egger’s test. Results A total of 45 studies involving 6,995 participants met the inclusion criteria; these included 25 countries covering Africa, Oceania, Europe, North America and Asia. The proportion of vitamin D deficiency in children/adolescents with T1D was 45% (95% confidence interval [CI] 37–54%, I 2 = 97.94%). Subgroup analysis further revealed that the publication year, study design, vitamin D classification, season and geographical region significantly contributed to the variation in the reported incidence of vitamin D deficiency. Conclusions The results of the meta-analysis showed that the proportion of vitamin D deficiency among T1D children/adolescents was 45%. In addition, the proportion remains higher, which has important implications for adapting health and social care systems.

Abstract Background Fatty liver disease causes huge economic losses in the poultry industry due to its high occurrence and lethality rate. Three-dimensional (3D) chromatin architecture takes part in disease processing by regulating transcriptional reprogramming. The study is carried out to investigate the alterations of hepatic 3D genome and H3K27ac profiling in early fatty liver (FLS) and reveal their effect on hepatic transcriptional reprogramming in laying hens. Results Results show that FLS model is constructed with obvious phenotypes including hepatic visible lipid deposition as well as higher total triglyceride and cholesterol in serum. A/B compartment switching, topologically associating domain (TAD) and chromatin loop changes are identified by high-throughput/resolution chromosome conformation capture (HiC) technology. Targeted genes of these alternations in hepatic 3D genome organization significantly enrich pathways related to lipid metabolism and hepatic damage. H3K27ac differential peaks and differential expression genes (DEGs) identified through RNA-seq analysis are also enriched in these pathways. Notably, certain DEGs are found to correspond with changes in 3D chromatin structure and H3K27ac binding in their promoters. DNA motif analysis reveals that candidate transcription factors are implicated in regulating transcriptional reprogramming. Furthermore, disturbed folate metabolism is observed, as evidenced by lower folate levels and altered enzyme expression. Conclusion Our findings establish a link between transcriptional reprogramming changes and 3D chromatin structure variations during early FLS formation, which provides candidate transcription factors and folate as targets for FLS prevention or treatment.

BackgroundHematopoietic stem cell transplantation (HSCT) is an approach that has significantly improved the prognosis and survival of hematological patients. However, ovarian dysfunction and infertility following HSCT have gained increasing attention. Live births have been reported following ovarian tissue cryopreservation prior to HSCT and subsequent retransplantation of these tissues. Still, the feasibility of ovarian tissue cryopreservation (OTC) following graft failure (GF) of HSCT remains unknown. In this study, we report the first case of OTC following a GF of allogenic HSCT (allo-HSCT), as well as the cryopreservation of four MII oocytes via in vitro maturation with informed consent. Despite the lack of clinical outcomes after cryopreserved ovarian tissue retransplantation, we documented an interesting case in a woman after GF of allo-HSCT exhibiting functional ovaries and emphasized a clinical dilemma: whether OTC should be offered to women suffering from GF of HSCT.Case presentationA 22-year-old woman with severe aplastic anemia who had suffered GF of allo-HSCT from her sibling brother [HLA allele match (7/10)] with a reduced dose conditioning regimen including fludarabine, cyclophosphamide, and antithymocyte globulin came to our reproductive center for fertility preservation, as she was about to receive the second allo-HSCT. We evaluated the ovarian reserve of this patient. Hormone assessments showed an anti-Müllerian hormone level of 3.921 ng/mL, a follicle-stimulating hormone level of 5.88 IU/L, a luteinizing hormone level of 10.79 IU/L, and an estradiol level of 33.34 pg/mL. Antral follicle counts accessed transvaginally showed 12–15 follicles. All assessments indicated a well-protected ovarian reserve. Due to the urgency of the second allo-HSCT, the patient decided to undergo ovarian cryopreservation. Laparoscopic surgery proceeded. Ovarian tissues were successfully cryopreserved using vitrification technology, and histologic evaluation demonstrated a follicle density of 20 per 2 × 2 mm2 biopsy with good viability. Four MII oocytes were obtained via in vitro maturation technology and cryopreserved. After the second HSCT, the patient relieved from aplastic anemia but suffered iatrogenic premature ovarian failure as predicted.ConclusionOTC is applicable to fertility preservation in those undergoing GF of HSCT with benign hematological disorders and especially those who are about to receive the second HSCT.

Lattice structures possess high specific strength, multi-functionality through innovative structural designs. Here, we proposed an efficient method for the construction of lattice structures by elongating two-dimensional planar patterns along the load direction, which enabled the efficient utilization of 100 % materials for load bearing. Inspired by Chinese Knot (CK), a series of meticulously crafted TC4 lattice structures were fabricated by using selective laser melting. These structures feature nine tubular units arranged in a 3 × 3 matrix interconnected by sixteen parallel plates, and their failure modes were subsequently investigated by uniaxial compression tests. The results show that the specific compressive strength of the CK structure enhances as increasing the density. The detachment between the plate and tube, and the buckling of the plate, lead to the premature failure, which in turn leads to substantial variations in strength, estimated at approximately 80 MPa at ∼ 1.5 g/cm3. When the thickness of the plate exceeds 0.5 mm, and the tube wall thickness exceeds 0.04 mm, the CK structures show high stability and exhibit a 45° shear failure mode. Notably, the specific strength of the CK structure can surpass 330 MPa∙cm3/g, which represents the peak level of specific compressive strength compared to the current TC4 lattice structures.

ObjectiveTo compare the effectiveness of radiomic features based on 18F-FDG PET/CT images within (intranodular) and around (perinodular) lung nodules/masses in distinguishing between lung adenocarcinoma and pulmonary granulomas.MethodsFor this retrospective study, 18F-FDG PET/CT images were collected for 228 patients. Patients diagnosed with lung adenocarcinoma (n = 156) or granulomas (n = 72) were randomly assigned to a training (n = 159) and validation (n = 69) groups. The volume of interest (VOI) of intranodular, perinodular (1–5 voxels, termed Lesion_margin1 to Lesion_margin5) and total area (intra- plus perinodular region, termed Lesion_total1 to Lesion_total5) on PET/CT images were delineated using PETtumor and Marge tool of segmentation editor. A total of 1,037 radiomic features were extracted separately from PET and CT images, and the optimal features were selected to develop radiomic models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC).ResultsGood and acceptable performance was, respectively, observed in the training (AUC = 0.868, p < 0.001) and validation (AUC = 0.715, p = 0.004) sets for the intranodular radiomic model. Among the perinodular models, the Lesion_margin2 model demonstrated the highest AUC in both sets (0.883 and 0.616, p < 0.001 and p = 0.122). Similarly, in terms of total models, Lesion_total2 model was found to outperform others in the training (AUC = 0.879, p < 0.001) and validation (AUC = 0.742, p = 0.001) sets, slightly surpassing the intranodular model.ConclusionWhen intra- and perinodular radiomic features extracted from the immediate vicinity of the nodule/mass up to 2 voxels distance on 18F-FDG PET/CT imaging are combined, improved differential diagnostic performance in distinguishing between lung adenocarcinomas and granulomas is achieved compared to the intra- and perinodular radiomic features alone.

IntroductionCOVID-19 constitutes a pandemic of significant detriment to human health. This study aimed to investigate the prevalence of Long COVID following SARS-CoV-2 infection, analyze the potential predictors of chest CT for the development of Long COVID in children.MethodsA cohort of children who visited the respiratory outpatient clinics at Shanghai Children's Medical Center or Linyi Maternal and Child Health Care Hospital from December 2022 to February 2023 and underwent chest CT scans within 1 week was followed up. Data on clinical characteristics, Long COVID symptoms, and chest CT manifestations were collected and analyzed. Multivariate logistic regression models and decision tree models were employed to identify factors associated with Long COVID.ResultsA total of 416 children were included in the study. Among 277 children who completed the follow-up, the prevalence of Long COVID was 23.1%. Chronic cough, fatigue, brain fog, and post-exertional malaise were the most commonly reported symptoms. In the decision tree model for Long COVID, the presence of increased vascular markings, the absence of normal CT findings, and younger age were identified as predictors associated with a higher likelihood of developing Long COVID in children. However, no significant correlation was found between chest CT abnormality and the occurrence of Long COVID.DiscussionLong COVID in children presents a complex challenge with a significant prevalence rate of 23.1%. Chest CT scans of children post-SARS-CoV-2 infection, identified as abnormal with increased vascular markings, indicate a higher risk of developing Long COVID.

ObjectiveDifficulties in emotion regulation (DERs) can contribute to disordered eating behavior in children and adolescents with type 1 diabetes (T1D), although it is unknown how DERs may affect eating behavior in these children and adolescents. This study examined the relationship between disordered eating behaviors and emotion regulation in children and adolescents with T1D.MethodsFor this cross-sectional study, 128 patients (aged 8–16 years) were recruited to complete the Diabetes Eating Problem Survey-Revised (DEPS-R) and Difficulties in Emotion Regulation Scale (DERs).ResultsThe mean age of the 128 patients (99 females) who completed the DEPS-R was 11.63 ± 2.27 years. The participants' mean DEPS-R score was 17.78 ± 8.56 points. Of the total sample, 61 participants' scores surpassed the established threshold, resulting in a DEPS-R positivity rate of 47.66%. The participants' mean total DERS score was 72.3 ± 21.15 points, and it was found that children and adolescents with T1D who had a positive DEPS-R screening result had significant differences in emotional regulation and that eating behavior disorders were positively correlated with emotional regulation and all dimensions scores.ConclusionsThe prevalence of disordered eating behavior is high among children and adolescents with T1D. DERs are related to disordered eating behavior in children and adolescents with T1D. The novel finding that DERs may be a predictor of eating problems lends preliminary support for the inclusion of DERs in future risk models and as a potential target for intervention.

ABSTRACT: The chicken comb is an essential secondary sexual characteristic to measure sexual maturity and is closely related to reproductive performance. Pendulous comb (PC) and upright comb (UC) are 2 common comb phenotypes in hens, which have been highly associated with egg production performance. However, the reasons for the formation of PC remain undetermined. In this study, we first characterized the PC and UC chicken at start (at 175 d age), peak (at 217 d age), and postlaying (at 300 d age) and found that PC and UC could transform for each other. Furthermore, we suggested that PC chicken demonstrated better egg production performance than UC chicken, especially characterizing comb type in the start-laying period. Moreover, we performed histological evaluation of PC and UC tissue, which suggested that the low density of collagen fibers and acid mucopolysaccharides might lead to the formation of PC. To further explore the possible reasons for PC formation, we performed an untargeted metabolomic analysis of serum between PC and UC chicken in the start, peak, and postlaying periods. The enrichment analysis of period-unique differentially expressed metabolites (DEMs) between PC and UC showed that the different metabolic pathways and nutritional levels might contribute to the formation of PC in the different laying periods. Our research provided critical insights into the phenotypic diversity of chicken comb, establishing a foundation for early selection of chicken egg production performance.

Background and purpose: In sliding-window intensity-modulated radiotherapy, increased plan modulation often leads to increased plan complexities and dose uncertainties. Dose calculation and/or measurement checks are usually adopted for pre-treatment verification. This study aims to evaluate the relationship among plan complexities, calculated doses and measured doses. Materials and methods: A total of 53 plan complexity metrics (PCMs) were selected, emphasizing small field characteristics and leaf speed/acceleration. Doses were retrieved from two beam-matched treatment devices. The intended dose was computed employing the Anisotropic Analytical Algorithm and validated through Monte Carlo (MC) and Collapsed Cone Convolution (CCC) algorithms. To measure the delivered dose, 3D diode arrays of various geometries, encompassing helical, cross, and oblique cross shapes, were utilized. Their interrelation was assessed via Spearman correlation analysis and principal component linear regression (PCR). Results: The correlation coefficients between calculation-based (CQA) and measurement-based verification quality assurance (MQA) were below 0.53. Most PCMs showed higher correlation rpcm-QA with CQA (max: 0.84) than MQA (max: 0.65). The proportion of rpcm-QA ≥ 0.5 was the largest in the pelvis compared to head-and-neck and chest-and-abdomen, and the highest rpcm-QA occurred at 1 %/1mm. Some modulation indices for the MLC speed and acceleration were significantly correlated with CQA and MQA. PCR’s determination coefficients (R2) indicated PCMs had higher accuracy in predicting CQA (max: 0.75) than MQA (max: 0.42). Conclusions: CQA and MQA demonstrated a weak correlation. Compared to MQA, CQA exhibited a stronger correlation with PCMs. Certain PCMs related to MLC movement effectively indicated variations in both quality assurances.

Background Behavioural and psychological symptoms of dementia (BPSD) are highly prevalent in people living with dementia. Second-generation antipsychotics (SGAs) are commonly used to treat BPSD, but their comparative efficacy and acceptability are unknown.Methods The standard mean difference (SMD) was used to pool the fixed effects of continuous outcomes. We calculated ORs with corresponding 95% credible intervals (CI) for the categorical variable. Efficacy was defined as the scores improved on the standardised scales. Acceptability was defined as the all-cause dropout rate. Tolerability was defined as the discontinuation rate due to adverse effects (AEs). The relative treatment rankings were reported with the surface under the cumulative curve. The AE outcomes included mortality, cerebrovascular adverse events (CVAEs), falls, sedation, extrapyramidal symptoms and urinary symptoms.Results Twenty randomised controlled trials with a total of 6374 individuals containing 5 types of SGAs (quetiapine, olanzapine, risperidone, brexpiprazole and aripiprazole) with intervention lengths ranging from 6 weeks to 36 weeks were included in this network meta-analysis. For the efficacy outcome, compared with the placebo, brexpiprazole (SMD=−1.77, 95% CI −2.80 to −0.74) was more efficacious, and brexpiprazole was better than quetiapine, olanzapine and aripiprazole. Regarding acceptability, only aripiprazole (OR=0.72, 95% CI 0.54 to 0.96) was better than the placebo, and aripiprazole was also better than brexpiprazole (OR=0.61, 95% CI 0.37 to 0.99). In terms of tolerability, olanzapine was worse than placebo (OR=6.02, 95% CI 2.87 to 12.66), risperidone (OR=3.67, 95% CI 1.66 to 8.11) and quetiapine (OR=3.71, 95% CI 1.46 to 9.42), while aripiprazole was better than olanzapine (OR=0.25, 95% CI 0.08 to 0.78). Quetiapine presented good safety in CVAE. Brexpiprazole has better safety in terms of falls and showed related safety in sedation among included SGAs.Conclusion Brexpiprazole showing great efficacy in the treatment of BPSD, with aripiprazole showing the highest acceptability and olanzapine showing the worst tolerability. The results of this study may be used to guide decision-making.

Abstract The DNA‐guided (gDNA) Argonaute from Thermus thermophilus (TtAgo) has little potential for nucleic acid detection and gene editing due to its poor dsDNA cleavage activity at relatively low temperature. Herein, the dsDNA cleavage activity of TtAgo is enhanced by using 2′‐fluorine (2′F)‐modified gDNA and developes a novel nucleic acid testing strategy. This study finds that the gDNA with 2′F‐nucleotides at the 3′‐end (2′F‐gDNA) can promote the assembly of the TtAgo‐guide‐target ternary complex significantly by increasing its intermolecular force to target DNA and TtAgo, thereby providing ≈40‐fold activity enhancement and decreasing minimum reaction temperature from 65 to 60 °C. Based on this outstanding advance, a novel nucleic acid testing strategy is proposed, termed FAST, which is performed by using the 2′F‐gDNA/TtAgo for target recognition and combining it with Bst DNA polymerase for nucleic acid amplification. By integrating G‐quadruplex and Thioflavin T, the FAST assay achieves one‐pot real‐time fluorescence analysis with ultra‐sensitivity, providing a limit of detection up to 5 copies (20 µL reaction mixture) for miR‐21 detection. In summary, an atom‐modification‐based strategy has been developed for enhancing the cleavage activity of TtAgo efficiently, thereby improving its practicability and establishing a TtAgo‐based nucleic acid testing technology with ultra‐sensitivity and high‐specificity.

ABSTRACT Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in Escherichia-Shigella (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery.IMPORTANCEOur pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.

Context: Ultrasound (US) is the most economical and widely used method for detecting lesions in parathyroid regions. Identifying typically parathyroid adenomas as hypoechoic nodules with clear margins. However, 10 % of lesions exhibit atypical features, such as the dual concentric sign, and the cognition of them still needs to be improved. Objective: To promote understanding of clinical and histopathological features for parathyroid lesions with the dual concentric echo sign and to investigate its pathogenesis and methods for distinguishing from cervical lymph nodes to improve US diagnostic accuracy. Methods: Retrospectively, patients were categorized into three groups: Group 1, with 36 patients showing parathyroid lesions with dual concentric echo signs; Group 2, with 40 patients displaying classic hypoechoic parathyroid lesions; and Group 3, comprising 36 patients with identified lymph nodes, which were all examined from January 2018 to December 2019. The clinical data on demographics, clinical symptoms, serum levels, histopathologic findings, and US image characteristics were thoroughly reviewed. Results: According to the clinical data, no significant differences in demographics or lesion sizes were observed in Group 1 and Group 2 (p > 0.05). No significant variances were noted in biochemical markers, including PTH, T-25OHD, and ALP. However, a notable difference was identified in adjusted serum calcium levels, which were significantly lower in Group 1 compared to Group 2 (p

IntroductionGranulocytic myeloid-derived suppressor cells (G-MDSCs) show fast recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) constituting the major part of peripheral blood in the early phase. Although G-MDSCs mediate immune suppression through multiple mechanisms, they may also promote inflammation under specific conditions. MethodsG-MDSCs were isolated from 82 patients following allo-HSCT within 90 days after allo-HSCT, and their interactions with autologous CD3+ T-cells were examined. T-cell proliferation was assessed by flow cytometry following CFSE staining, while differentiation and interferon-γ secretion were characterized using chemokine receptor profiling and ELISpot assays, respectively. NK cell cytotoxicity was evaluated through co-culture with K562 cells. An aGVHD xenogeneic model in humanized mice was employed to study the in vivo effects of human leukocytes. Furthermore, transcriptional alterations in G-MDSCs were analyzed via RNA sequencing to investigate functional transitions.ResultsG-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing grades II-IV aGvHD. Besides, adoptive transfer of G-MDSCs from patients at day 28 into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs led to immunosuppression, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that 1445 genes were differentially expressed. These genes were associated with various pathways, revealing the molecular signatures of early post-transplant differentiation in G-MDSCs. In addition, genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. The acquisition of immunosuppressive function by G-MDSCs may depend on the activation of CXCL2 and DERL1 genes. ConclusionOur findings revealed the alteration in the immune characteristics of G-MDSCs within the first 90 days post-allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 may serve as a predictive indicator for the development of aGvHD.

ObjectiveWe aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC).MethodsMDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes.ResultsOur findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC.ConclusionMDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.

Summary: Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.

Manganese (Mn) exposure is a common environmental risk factor for Parkinson's disease (PD), with pathogenic mechanisms associated with dopaminergic neuron damage and neuroinflammation. Mesenchymal stem cells (MSCs)-derived small extracellular vesicles (sEVs) have emerged as a novel therapeutic approach for neural damage repair. The functional sEVs released from MSCs when they are induced into dopaminergic progenitors may have a better repair effect on neural injury. Therefore, we collected sEVs obtained from primary human nasal mucosal mesenchymal stem cells (hnmMSC-sEVs) or cells in the process of dopaminergic progenitor cell differentiation (da-hnmMSC-sEVs), which were cultured in a 3D dynamic system, and observed their repair effects and mechanisms of Mn-induced neural damage by intranasal administration of sEVs. In Mn-exposed mice, sEVs could reach the site of brain injury after intranasal administration, da-hnmMSC enhanced the repair effects of sEVs in neural damage and behavioral competence, as evidenced by restoration of motor dysfunction, enhanced neurogenesis, decreased microglia activation, up-regulation of anti-inflammatory factors, and down-regulation of pro-inflammatory factors. The transcriptomics of hnmMSC-sEVs and da-hnmMSC-sEVs revealed that miRNAs, especially miR-494–3p in sEVs were involved in neuroprotective and anti-inflammatory effects. Overexpression of miR-494–3p in sEVs inhibited Mn-induced inflammation and neural injury, and its repair mechanism might be related to the down-regulation of CMPK2 and NLRP3 in vitro experiments. Thus, intranasal delivery of da-hnmMSC-sEVs is an effective strategy for the treatment of neural injury repair.

Cement production consumes large amounts of depleted resources and energy, and causes environmental pollution. In order to reduce cement consumption and realize the closed-loop recycling of solid waste, cold bonded solid waste wrap-shell lightweight aggregates (SWSLAs) with a sextuplet blended system composed of dredged sediments, mineral powder, steel slag, phosphogypsum, fly ash, and a minimal amount of cement were prepared. Through the single-factor experiment, the influences of the types and dosages of solid wastes in the nuclear phase of SWSLAs (SWSLAs-NP) and shell phase of SWSLAs (SWSLAs-SP) on the strength and water resistance were explored, and the optimum ratio was obtained. On this basis, the influence of the types and amounts of activators incorporated in SWSLAs on the physical properties of aggregates was studied, and the primary microstructure of the aggregate was characterized. Our results showed that the optimal ratio of solid waste in the SWSLAs-NP was: 40 wt% of dredged sediments, 24 wt% of mineral powder, 18 wt% of steel slag, and 18 wt% of phosphogypsum. The optimal weight ratio of cement and solid waste in the SWSLAs-SP was 5:95. The resulting aggregate had a bearing capacity of single grain of 73.83 N and a water-resistance coefficient of 0.67. After the above aggregates were treated with Na2SO4 (activator) at 2%, the bearing capacity and water-resistance coefficient of the aggregates increased by 47.00% and 11.94%, respectively. The performances were even better than that of the aggregate composed of100w cement in the shell phase. Microstructural observations demonstrated that the structure of the raw material was reconstructed under the action of Na2SO4, and the raw materials reacted with each other, and thus the densification of the aggregate and its core-shell interface structure was enhanced, which improved the comprehensive performance of the aggregate. This study represents a step toward efficient utilization of industrial solid wastes.

BackgroundThis systematic review and meta-analysis aims to investigate the effects of virtual reality (VR) exercise compared to traditional rehabilitation on pain, function, and muscle strength in patients with knee osteoarthritis (KOA). Additionally, the study explores the mechanisms by which VR exercise contributes to the rehabilitation of KOA patients.MethodsWe systematically searched PubMed, the Cochrane Library, Embase, Web of Science, Scopus, and PEDro according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search spanned from the library construction to 24 May 2024, focusing on randomized controlled trials Primary outcomes included pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and muscle strength. Meta-analysis was conducted using RevMan (version 5.4) and Stata (version 14.0). The bias risk of included studies was assessed using the Cochrane RoB 2.0 tool, while the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.ResultsThis meta-analysis and systematic review included nine studies involving 456 KOA patients. The results indicated that VR exercise significantly improved pain scores (SMD, −1.53; 95% CI: −2.50 to −0.55; p = 0.002), WOMAC total score (MD, −14.79; 95% CI: −28.26 to −1.33; p = 0.03), WOMAC pain score (MD, −0.93; 95% CI: −1.52 to −0.34; p = 0.002), knee extensor strength (SMD, 0.51; 95% CI: 0.14 to 0.87; p = 0.006), and knee flexor strength (SMD, 0.65; 95% CI: 0.28 to 1.01; p = 0.0005), but not significantly for WOMAC stiffness (MD, −0.01; 95% CI: −1.21 to 1.19; p = 0.99) and physical function (MD, −0.35; 95% CI: −0.79 to −0.09; p = 0.12).ConclusionVR exercise significantly alleviates pain, enhances muscle strength and WOMAC total score in KOA patients, but improvements in joint stiffness and physical function are not significant. However, the current number of studies is limited, necessitating further research to expand on the present findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024540061, identifier CRD42024540061

BackgroundIcanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR1. In this first-in-human study, icanbelimod was investigated in healthy men in Australia.MethodsParticipants were randomized 3:1, double-blind, to icanbelimod or placebo in four single-dose cohorts (0.1 mg, 0.25 mg, 0.5 mg [n=8 per cohort], 2.5 mg [n=4]) or for 28-days once-daily treatment in two cohorts (0.15 mg, 0.25 mg [n=8 per cohort]). Participants in the 0.25-mg cohort received 0.1 mg on Day 1. Treatments were administered orally after fasting; following one-week washout, icanbelimod was administered after breakfast in the 0.5-mg cohort.ResultsIcanbelimod exposure increased rapidly and dose-dependently with single and multiple dosing (Tmax 4–7 hours). Lymphocyte counts decreased rapidly after single (-11%, 0.1 mg; -40%, 0.25 mg; -71%, 0.5 mg; -77%, 2.5 mg) and multiple doses (-49%, 0.15 mg; -75%, 0.25 mg), and recovered quickly, 7 days after dosing. After single-dose 0.5 mg, although a high-fat breakfast versus fasting did not affect maximal decrease, lymphocyte counts tended to be lower after breakfast across most timepoints up to 72 hours. Twenty-eight participants (63.6%) experienced mainly mild treatment-emergent adverse events (TEAEs). After single-dose icanbelimod, the most common TEAEs were headache (28.6%, n=6) and dizziness (19.0%, n=4). Three participants experienced transient bradycardia, with one serious, following single-dose 2.5 mg icanbelimod. After multiple-dose icanbelimod, the most common TEAEs were headache (50.0%, n=6) and lymphopenia (41.7%, n=5), and two participants withdrew due to non-serious TEAEs. Up-titration attenuated heart rate reductions.ConclusionIcanbelimod was well-tolerated up to 0.5 mg and effectively reduced lymphocyte counts.Clinical trial registrationClinicalTrials.gov, identifier NCT02280434.b