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ABSTRACT: Traditional fermented milks are produced through an inoculation process that involves the deliberate introduction of microorganisms that have been adapted and perpetuated across successive generations. However, the changes in the microbiota of traditional fermented milk during long-term inoculation fermentation in a laboratory environment remain unclear. In this study, we collected 5 samples of traditional fermented milk samples from 5 different counties in Tibet (3 kurut products) and Xinjiang (2 tarag products) of China, which served as starter cultures for a 9-mo continuous inoculation fermentation experiment. We analyzed the inter- and intrapopulation variations in the microbial communities of the collected samples, representing their macrodiversity and microdiversity, using shotgun metagenomic sequencing. Across all samples, we obtained a total of 186 high-quality metagenomic-assembled genomes, including 7 genera and 13 species with a relative abundance of more than 1%. The majority of these genomes were annotated as Lactobacillus helveticus (60.46%), Enterococcus durans (9.52%), and Limosilactobacillus fermentum (6.23%). We observed significant differences in species composition and abundance among the 5 initial inoculants. During the long-term inoculation fermentation, we found an overall increasing trend in species diversity, composition, and abundances of carbohydrate metabolism module-encoding genes in the fermented milk bacterial metagenome, while the fermented milk virome exhibited a relatively narrow range of variation. Lactobacillus helveticus, a dominant species in traditional fermented milk, displayed high stability during the long-term inoculation fermentation. Our study provides valuable insights for the industrial production of traditional fermented milk.

The northwestern region in China has the characteristics of large coal seam thickness and shallow burial depth. Unmanned aerial vehicle (UAV) thermal infrared monitoring and temperature compensation are key technologies for monitoring shallow coal fire disasters, which is of great significance for advancing the safety monitoring and warning evaluation of coal spontaneous combustion disasters. A temperature compensation model based on the grey wolf optimization-double-layer generalized regression neural network (GWO-double-layer GRNN) and continuous altitude correction function is proposed to address the influence of multiple parameters on thermal infrared temperature monitoring results in complex environments. The factors affecting the temperature results under the thermal infrared monitoring band are selected based on the contrast of the atmospheric extinction coefficient to the received radiation, and the index factors that can cumulatively characterize the actual temperature are determined by principal component analysis. The index factor data from the UAV thermal infrared monitoring experiments in various environments are used as inputs to the GWO-double-layer GRNN network to obtain a discretely trained temperature compensation model. A continuous correction function for UAV altitude is proposed as a pre-processing step for the model input to compensate for the data, and the complete temperature compensation model is tested and field-validated. The results show that the discrete compensation effect of the GWO-double-layer GRNN network is superior to other models in data testing, with MAE ≤ 0.008 1, RMSE ≤ 0.013 2, and R2 ≥ 0.996 9, indicating that the model has good compensation effects. The continuous correction function avoids the influence of UAV altitude on thermal infrared monitoring results, dividing the problem of UAV continuous altitude thermal infrared temperature regression into a stepwise regression calculation, and the final model has a good monitoring accuracy, improving the generalization ability of the temperature compensation model. It provides a supporting calculation method for applying UAV thermal infrared monitoring results to delineate shallow coal fire hazard areas and further promote this method to the corresponding UAV applications and laser monitoring industry.

Abstract This study aims to evaluate the biomechanical performance of the Gamma 3 nail with an anti-rotation screw (GNS) and compare it to two established gold-standard methods for treating unstable femoral neck fractures (UFNFs). Synthetic bone models were prepared with Pauwels’ type III osteotomy and an additional posterior wedge. Three different implant configurations were tested: three cannulated crews (3CS) in an inverted triangle configuration, a dynamic hip screw with an anti-rotation screw (DHSS), and GNS. Non-destructive cyclic axial loading was applied at 7° adduction, with 1000 cycles ranging from 100 to 1000 N. Subsequently, a construct failure test was conducted using progressive axial compression, and fracture reduction loss was recorded. The average axial stiffness was 321 ± 52 N/mm for 3CS, 430 ± 71 N/mm for DHSS, and 519 ± 104 N/mm for GNS. The average ultimate failure loads were 2699.3 N for 3CS, 3427.1 N for DHSS, and 3758.9 N for GNS. GNS demonstrated significantly greater axial stiffness compared to the other two groups (P

Abstract Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.

In order to study the factors affecting the ignition risk parameters of pulverized coal cloud, Godbert-Greenwald constant temperature furnace was used to test the minimum ignition temperature of pulverized coal cloud under different particle size, mass concentration and powder injection pressure conditions. The results show that the minimum ignition temperature increases with the increase of particle size. In the range of 0.250−0.667 kg/m3, the mass concentration of pulverized coal decreases with the increase of mass fraction, and the minimum value is 545 ℃. With the increase of dusting pressure, it changes in the shape of “V”. The degree of influence of the three factors on the minimum ignition temperature is as follows: mass fraction > powder injection pressure > coal particle size.

Abstract Aerosol jet printing has the potential to fabricate fine features on various substrates due to its large stand-off distance. However, the presence of overspray and instability, particularly at high printing resolutions, has limited its widespread application. In this study, we introduce an efficient approach called annular acoustic focusing for aerosol jet printing. By determining the optimal focusing frequency (5.8 MHz) for silver nanoparticles using a particle ejection model, we achieve precise and stable printing. We also propose a modified print nozzle geometry, resulting in ultrafine traces (line width

Wind farm wakes have a significant impact on momentum and turbulence fluxes within the atmospheric boundary layer， thereby influencing the local climate and environment.Mesoscale numerical models incorporating wind farm parameterizations are powerful tools for studying the climate and environmental impacts of wind farms.In this study， the wind speed and turbulence kinetic energy profiles of the Fitch wind farm parameterization scheme in the WRF mesoscale model are evaluated in the turbine and wake regions using high-resolution Large Eddy Simulations （LES） as “true values” and a method based on the relation derived from classical momentum theory is proposed to correct the grid-inflow wind speed.The method takes into account the blocking effect caused by the grid equivalent thrust and the corrected wind speed is closer to the free-stream wind speed.Results show that the difference between the grid-inflow wind speed from the original Fitch parameterization scheme and the LES is significant and sensitive to the model horizontal resolution.The Fitch-new parameterization with corrected grid-inflow wind speed reduces the relative error in absolute value between grid-inflow and free-stream wind speed to less than 1% across different horizontal resolutions （1000 m， 500 m， and 250 m）.The spatially averaged thrust and output power are consistent with LES results.The Fitch-new parameterization improves the simulated wind speed deficit in the wake zone of wind turbine， especially in the grid with turbine under high resolution.Although the simulated increase in turbulent kinetic energy and its vertical distribution in the wake zone is improved compared to the original Fitch scheme， there are certain issues that require further investigation.

Abstract Aim The clinical characteristics associated with pulmonary function decline in patients with Tuberculosis-destroyed lung (TDL) remain uncertain. We categorize them based on the pattern of pulmonary function impairment, distinguishing between restrictive spirometric pattern (RSP) and obstructive spirometric pattern (OSP). We aim to compare the severity of these patterns with the clinical characteristics of TDL patients and analyze their correlation. Method We conducted a retrospective analysis on the clinical data of TDL patients who underwent consecutive pulmonary function tests (PFT) from November 2002 to February 2023. We used the lower limit formula for normal values based on the 2012 Global Lung Function Initiative. We compared the clinical characteristics of RSP patients with those of OSP patients. The characteristics of RSP patients were analyzed using the tertiles of forced vital capacity percentage predicted (FVC% pred) decline based on PFT measurements, and the characteristics of OSP patients were analyzed using the tertiles of forced expiratory volume in 1 s percentage predicted (FEV1% pred) decline. Result Among the RSP patients, those in the Tertile1 group (with lower FVC% pred) were more likely to have a higher of body mass index (BMI), spinal deformities, and C-reactive protein (CRP) compared to the other two groups (P for trend

Abstract Titanium (Ti) dental scaffolds are widely used in dental prosthetics due to their excellent mechanical properties and biocompatibility. However, conventional Ti scaffolds manufactured through machining often do not fit perfectly with the bone defect site. Laser powder bed fusion (LPBF) technology enables the personalised manufacturing of custom‐made Ti scaffolds. A custom‐made Ti scaffold was prepared using LPBF and its surface roughness was improved through chemical polishing. To enhance the surface roughness, a nitric acid mixed solution with a specific composition of HF: HNO3:C3H6O3 = 2:2:3 was used. The polishing mechanism was investigated by adjusting the F/Ti ratio to control the formation and dissolution of the oxide film. As a result, the surface of the Ti scaffold after polishing exhibited a smooth and flat appearance compared to the LPBF part, with a reduced surface roughness (Ra) of 1.23 ± 0.19 μm. The custom‐made Ti scaffold also demonstrated favourable mechanical properties, with a bending strength of 335.18 ± 33.62 MPa and stiffness of 2.13 ± 0.21 GPa. Furthermore, in vitro cell tests confirmed the excellent biocompatibility of the custom‐made Ti scaffold. The authors present a feasible strategy for the further clinical application of custom‐made Ti scaffolds, offering enhanced surface properties and addressing the limitations of conventional machining methods.

AIM: To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD). METHODS: A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n=15) or rituximab (Group RTX, n=18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes. RESULTS: Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (P0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections. CONCLUSION: The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Pseudoaneurysm of the internal iliac artery is a very rare complication of intertrochanteric fracture. Here, the case of an 88-year-old female patient, who presented with intense pain following surgery for intertrochanteric fracture of the femur, is reported. Radiography revealed intertrochanteric fracture of the left femur fixed by proximal femoral nail antirotation (PFNA). The PFNA was found to have disassembled, and the screw had penetrated through the acetabulum. As computed tomography (CT) revealed a haematoma behind the acetabulum, CT angiography was immediately performed. A pseudoaneurysm of the internal iliac artery caused by PFNA was revealed. Percutaneous endovascular treatment of the pseudoaneurysm was undertaken on an urgent basis. Three days later, the PFNA was removed, and the fracture was reduced and fixed with locking proximal femoral plate. The patient’s pain was significantly reduced following this corrective surgery. This case illustrates that substandard PFNA surgery for intertrochanteric fracture may result in pseudoaneurysm of the internal iliac artery.

To research the impact of oxygen consistency on the thermal dynamic characteristics and the change of gas products of weakly caking coal oxidation, differential scanning calorimetry and temperature programmed experiments were used to study, and the correlation between the intensity of heat release at distinct consistencies of oxygen and concentration of gas products was computed applying grey correlation method. The outcomes indicated that the coal low-temperature oxidation process can be categorized into three phases: speedy endothermic, slow endothermic, and exothermic. The apparent activation energy in the slow heat absorption phase exceeded the speedy endothermic stage, and the apparent activation energy in the heat release phase increased by 20.83 kJ/mol. The concentration of gas products generated at the spontaneous combustion process of coal growth when temperature went up. However, CH4 concentration increased with the temperature rising after 120 °C. C2H6 gas does not appear until 100 °C. C2H4 gas appeared after 90 °C. At various O2 consistencies, the correlation between exothermic intensity and CO2 remained the largest, the correlation between exothermic intensity and CO and CH4 was larger at lower oxygen consistencies. As concentration of oxygen increased, the correlation between exothermic intensity and C2H4 and C2H6 increased first and then decreased.

Abstract The rapid evolution of clinical medicine, materials science, and regenerative medicine has rendered traditional implantable scaffolds inadequate for addressing the complex therapeutic demands of various diseases. Currently, implantable scaffolds in clinical practice are mainly made of metal, with the disadvantages of high stiffness, poor toughness, and low deformation. This paper offers a thorough review of shape memory scaffolds (SMSs), emphasizing their distinctive self‐recovery and adaptive functionalities that enhance compatibility with injured tissues, surpassing the capabilities of conventional metallic biomaterials. It delves into the limitations of current clinical scaffolds and the requisite performance metrics for effective implants and outlines the essential materials and fabrication methods for SMSs. Moreover, we enumerate the biomedical applications of SMMs with different response types, including thermology‐responsive, water‐responsive, and light‐responsive. The discussion extends to the burgeoning applications of SMSs in biomedical engineering, including their utility in bone tissue engineering, cardiovascular stenting, tubular structures, and cardiac patches, which underscore their potential in minimally invasive procedures and dynamic tissue interactions. This review concludes with an analysis of current challenges and prospects, providing valuable insights for developing and applying SMSs in the biomedical sector.

Background: Cognitive impairment is a common manifestation in patients with T2DM mellitus (T2DM). Ginsenoside Rg1 (GRg1) is the main active substance extracted from ginseng or Panax notoginseng. Methods: T2DM was induced by feeding rats with a high-sugar and high-fat diet combined with a low-dose intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) on an empty stomach. Subsequently, different concentrations of GRg1 (25, 50, 100 mg/kg/d) were used to intervene for 8 weeks and explore its therapeutic effects and potential mechanisms on cognitive impairment in T2DM rats. Results: Our data suggested that administration of GRg1 improved insulin resistance, specifically manifesting in a reduction of insulin resistance index by approximately 57.1 % with high doses of GRg1 (100 mg/kg/d). Besides, it has been observed to lower cholesterol, triglycerides, and low-density lipoprotein by approximately 20–50 % in T2DM rats. In addition, GRg1 treatment dramatically improved the spatial memory and learning ability in T2DM rats. Furthermore, administration of GRg1 to the T2DM rats dose-dependently up-regulated ERKs phosphorylation and blunted phosphorylation of JNKs and p38. Furthermore, GRg1 treatment also dose-dependently increased the expression of Bcl-2 but inhibited the expression of Bax and Caspase 3 expression in T2DM rats brain cortex and hippocampus neurons. Conclusion: GRg1 effectively improves mild cognitive impairment in T2DM rats by inhibiting oxidative stress and reducing the apoptosis of neurons in the cerebral cortex and hippocampus.

This study takes Guanshan River Basin, a typical inflow river of the Danjiangkou Reservoir, as the research area, and the nonpoint source (NPS) pollution characteristics of nitrogen and phosphorus from 2013 to 2018 were evaluated by establishing a Soil and Water Assessment Tool (SWAT) model. The pollution characteristics of heavy metals were also evaluated by combining the SWAT and simple output coefficient method. The results show that the pollutant load in Guanshan River Basin contributes significantly to the Danjiangkou Reservoir. Temporally, pollutant loads were primarily concentrated in the flood season, which had a significant positive correlation with precipitation, water yield, and sediments in the abundant period. Among them, sediments were the most important driving factor, followed by water yield. Spatially, pollutant loads were mainly concentrated downstream of the basin, where cultivated land is widespread. In this regard, it is suggested that the input of chemical fertilizers, pesticides, and livestock manure in cultivated land should be controlled and soil erosion downstream of the basin should be prevented to mitigate nitrogen, phosphorus, and heavy metal pollution. This research offers a basis for the formulation and implementation of watershed management for the Danjiangkou Reservoir. HIGHLIGHTS Based on the Soil and Water Assessment Tool model, the nonpoint source (NPS) pollution features and sources of nitrogen, phosphorus, and heavy metals were analyzed and discussed.; The NPS pollution is mainly concentrated in the flood season, and sediment is the most important driving factor, followed by water yield.; The input of fertilizers and pesticides into cultivated land should be controlled, and soil erosion should be prevented in the study's high-load area.;

Abstract How to deal with large tibial bone defects is still controversial. The purpose of this research was to compare the semi-focal bone transport (SFBT) technique with traditional bone transport (TBT) technique for treating such patients. Sixty-two patients were included and retrospectively analyzed. In all cases, after radical debridement large tibial bone defects remained. Patients were treated by the SFBT or TBT technique. The distraction, consolidation duration and complications were recorded by the patients’ medical files. Based on the Association for the Study and Application of Methods of Ilizarov (ASAMI) standard, the bone and functional results were evaluated. The mean bone defect size was 7.7 ± 1.6 cm and 7.5 ± 2.1 cm for SFBT and TBT patients. The mean external fixation index (EFI) was 1.51 ± 0.14 months/cm and 1.89 ± 0.25 months/cm for SFBT and TBT patients (p 0.05). The mean number of complications per patient was 1.1 ± 0.6 and 1.6 ± 0.7 for SFBT and TBT patients (p

Abstract Hypertrophic scar (HS) considerably affects the appearance and causes tissue dysfunction in patients. The low bioavailability of 5-fluorouracil poses a challenge for HS treatment. Here we show a separating microneedle (MN) consisting of photo-crosslinked GelMA and 5-FuA-Pep-MA prodrug in response to high reactive oxygen species (ROS) levels and overexpression of matrix metalloproteinases (MMPs) in the HS pathological microenvironment. In vivo experiments in female mice demonstrate that the retention of MN tips in the tissue provides a slowly sustained drug release manner. Importantly, drug-loaded MNs could remodel the pathological microenvironment of female rabbit ear HS tissues by ROS scavenging and MMPs consumption. Bulk and single cell RNA sequencing analyses confirm that drug-loaded MNs could reverse skin fibrosis through down-regulation of BCL-2-associated death promoter (BAD), insulin-like growth factor 1 receptor (IGF1R) pathways, simultaneously regulate inflammatory response and keratinocyte differentiation via up-regulation of toll-like receptors (TOLL), interleukin-1 receptor (IL1R) and keratinocyte pathways, and promote the interactions between fibroblasts and keratinocytes via ligand-receptor pair of proteoglycans 2 (HSPG2)-dystroglycan 1(DAG1). This study reveals the potential therapeutic mechanism of drug-loaded MNs in HS treatment and presents a broad prospect for clinical application.

Population density estimation is integral to the effective conservation and management of wildlife. The snow leopard Panthera uncia is categorized as Vulnerable on the IUCN Red List, and reliable information on its density is a prerequisite for its conservation and management. Little is known about the status of the snow leopard in the central and eastern Qilian Mountains, China. To address this, we estimated the population density of the snow leopard using a spatially explicit capture–recapture model based on camera trapping in Machang in the central and eastern Qilian Mountains during January–March 2019. We set up 40 camera traps and recorded 84 separate snow leopard captures over 3,024 trap-days. We identified 18 individual snow leopards and estimated their density to be 2.26/100 km2. Our study provides baseline information on the snow leopard and the first population estimate for the species in the central and eastern Qilian Mountains.

Chronic diarrhea has a considerable impact on quality of life. This randomized, double-blind, placebo-controlled crossover intervention trial was conducted with 69 participants (36 in Group A, 33 in Group B), aiming to investigate the potential of postbiotics in alleviating diarrhea-associated symptoms. Participants received postbiotic Probio-Eco® and placebo for 21 days each in alternating order, with a 14-day washout period between interventions. The results showed that postbiotic intake resulted in significant improvements in Bristol stool scale score, defecation frequency, urgency, and anxiety. Moreover, the postbiotic intervention increased beneficial intestinal bacteria, including Dysosmobacter welbionis and Faecalibacterium prausnitzii, while reducing potential pathogens like Megamonas funiformis. The levels of gut Microviridae notably increased. Non-targeted metabolomics analysis revealed postbiotic-driven enrichment of beneficial metabolites, including α-linolenic acid and p-methoxycinnamic acid, and reduction of diarrhea-associated metabolites, including theophylline, piperine, capsaicin, and phenylalanine. Targeted metabolomics confirmed a significant increase in fecal butyric acid after postbiotic intervention. The levels of aromatic amino acids, phenylalanine and tryptophan, and their related metabolites, 5-hydroxytryptophan and kynurenine, decreased after the postbiotic intervention, suggesting diarrhea alleviation was through modulating the tryptophan-5-hydroxytryptamine and tryptophan-kynurenine pathways. Additionally, chenodeoxycholic acid, a diarrhea-linked primary bile acid, decreased substantially. In conclusion, postbiotics have shown promise in relieving chronic diarrhea.

BackgroundThe infant gut microbiome’s establishment is pivotal for health and immune development. Understanding it unveils insights into growth, development, and maternal microbial interactions. Research often emphasizes gut bacteria, neglecting the phageome.MethodsTo investigate the influence of geographic or maternal factors (mode of delivery, mode of breastfeeding, gestational diabetes mellitus) on the gut microbiota and phages of newborns, we collected fecal samples from 34 pairs of mothers and their infants within 24 hours of delivery from three regions (9 pairs from Enshi, 7 pairs from Hohhot, and 18 pairs from Hulunbuir) using sterile containers. Gut microbiota analysis by Shotgun sequencing was subsequently performed.ResultsOur results showed that geographic location affects maternal gut microbiology (P < 0.05), while the effect on infant gut microbiology was not significant (P = 0.184). Among the maternal factors, mode of delivery had a significant (P < 0.05) effect on the newborn. Specific bacteria (e.g., Bacteroides, Escherichia spp., Phocaeicola vulgatus, Escherichia coli, Staphylococcus hominis, Veillonella spp.), predicted active metabolites, and bacteriophage vOTUs varied with delivery mode. Phocaeicola vulgatus significantly correlated with some metabolites and bacteriophages in the early infant gut (P < 0.05). In the GD group, a strong negative correlation of phage diversity between mother and infants was observed (R = -0.58, P=0.04).ConclusionIn conclusion, neonatal early gut microbiome (including bacteria and bacteriophages) colonization is profoundly affected by the mode of delivery, and maternal gestational diabetes mellitus. The key bacteria may interact with bacteriophages to influence the levels of specific metabolites. Our study provides new evidence for the study of the infant microbiome, fills a gap in the analysis of the infant gut microbiota regarding the virome, and emphasizes the importance of maternal health for the infant initial gut virome.

Given the prevalence of Al/RDX energetic dust in industrial production, this study investigates their ignition safety and explosion hazards using Hartmann tubes and 20 L spherical explosion containers. The minimum ignition energy (MIE) increases from 20 mJ to 55 mJ as RDX content increases, indicating that adding RDX enlarges the effective particle size of the dust, thereby reducing its ignition sensitivity. A logistic regression model was used to develop a fitting equation for ignition probability, correlating dust concentration and ignition energy. The flame propagation velocity and explosion pressure of the energetic dust initially increase and then decrease with increasing RDX content. Optimal combustion characteristics were observed at 20 % RDX, with the maximum flame propagation velocity of 101 m s−1. However, the peak flame temperature decreases with increasing RDX content. The maximum explosion pressure and maximum explosion index at 1.77 MPa and 186.99 MPa m s−1 respectively, at 40 % RDX content. These findings highlight that 20 % RDX content yields the best combustion characteristics, while 40 % RDX content offers the maximum explosive potential, providing valuable insights for enhancing safety measures in industrial applications involving energetic dusts.

Abstract The DNA‐dependent protein kinase (DNA‐PK), catalytic subunit, also known as DNA‐PKcs, is complexed with the heterodimer Ku70/Ku80 to form DNA‐PK holoenzyme, which is well recognized as initiator in the nonhomologous end joining (NHEJ) repair after double strand break (DSB). During NHEJ, DNA‐PKcs is essential for both DNA end processing and end joining. Besides its classical function in DSB repair, DNA‐PKcs also shows multifaceted functions in various biological activities such as class switch recombination (CSR) and variable (V) diversity (D) joining (J) recombination in B/T lymphocytes development, innate immunity through cGAS–STING pathway, transcription, alternative splicing, and so on, which are dependent on its function in NHEJ or not. Moreover, DNA‐PKcs deficiency has been proven to be related with human diseases such as neurological pathogenesis, cancer, immunological disorder, and so on through different mechanisms. Therefore, it is imperative to summarize the latest findings about DNA‐PKcs and diseases for better targeting DNA‐PKcs, which have shown efficacy in cancer treatment in preclinical models. Here, we discuss the multifaceted roles of DNA‐PKcs in human diseases, meanwhile, we discuss the progresses of DNA‐PKcs inhibitors and their potential in clinical trials. The most updated review about DNA‐PKcs will hopefully provide insights and ideas to understand DNA‐PKcs associated diseases.

Abstract Solution‐processed 2D materials hold promise for their scalable applications. However, the random, fragmented nature of the solution‐processed nanoflakes and the poor percolative conduction through their discrete networks limit the performance of the enabled devices. To overcome the problem, conduction modulation of the solution‐processed 2D materials is reported via Stark effect. Using liquid‐phase exfoliated molybdenum disulfide (MoS2) as an example, nonlinear conduction switching with a ratio of >105 is demonstrated by the local fields from the interfacial ferroelectric P(VDF‐TrFE). Through density‐functional theory calculations and in situ Raman scattering and photoluminescence spectroscopic analysis, the modulation is understood to arise from a charge redistribution in the solution‐processed MoS2. Beyond MoS2, the modulation may be shown effective for the other solution‐processed 2D materials and low‐dimensional materials. The modulation can open their electronic device applications, for instance, thin‐film nonlinear electronics and non‐volatile memories.

Abstract The Electron-Ion Collider (EIC), a forthcoming powerful high-luminosity facility, represents an exciting opportunity to explore new physics. In this article, we study the potential of the EIC to probe the coupling between axion-like particles (ALPs) and photons in coherent scattering. The ALPs can be produced via photon fusion and decay back to two photons inside the EIC detector. In a prompt-decay search, we find that the EIC can set the most stringent bound for m a ≲ 20 GeV and probe the effective scales Λ ≲ 105 GeV. In a displaced-vertex search, which requires adopting an EM calorimeter technology that provides directionality, the EIC could probe ALPs with m a ≲ 1 GeV at effective scales Λ ≲ 107 GeV. Combining the two search strategies, the EIC can probe a significant portion of unexplored parameter space in the 0.2 < m a < 20 GeV mass range.

Abstract Chemoenzymatic cascade catalysis has emerged as a revolutionary tool for streamlining traditional retrosynthetic disconnections, creating new possibilities for the asymmetric synthesis of valuable chiral compounds. Here we construct a one-pot concurrent chemoenzymatic cascade by integrating organobismuth-catalyzed aldol condensation with ene-reductase (ER)-catalyzed enantioselective reduction, enabling the formal asymmetric α-benzylation of cyclic ketones. To achieve this, we develop a pair of enantiocomplementary ERs capable of reducing α-arylidene cyclic ketones, lactams, and lactones. Our engineered mutants exhibit significantly higher activity, up to 37-fold, and broader substrate specificity compared to the parent enzyme. The key to success is due to the well-tuned hydride attack distance/angle and, more importantly, to the synergistic proton-delivery triade of Tyr28-Tyr69-Tyr169. Molecular docking and density functional theory (DFT) studies provide important insights into the bioreduction mechanisms. Furthermore, we demonstrate the synthetic utility of the best mutants in the asymmetric synthesis of several key chiral synthons.

A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective Hip fractures are the most common fractures among older adults, with most patients undergoing surgery. The debate regarding the type of anesthetic technique for hip fracture surgery is still ongoing. This meta‐analysis aimed to compare the intraoperative and postoperative outcomes of spinal and general anesthesia in older patients undergoing hip fracture surgery. Methods Eligible studies that compared the effects of spinal and general anesthesia were systematically searched from PubMed, Embase, and the Cochrane Library until May 27, 2022. The intraoperative and postoperative outcomes of the two anesthesia techniques were compared. Quality assessment, heterogeneity analysis, and publication bias of the studies were also assessed. Results Nine articles of methodological quality were included in the meta‐analysis. The pooled results revealed that there were significant differences in hypotension (risk ratio [RR] (95% confidence interval [CI]) = 0.81 (0.68, 0.97), p = 0.02) and ephedrine dose (weighted mean difference [WMD] [95%CI] = −20.94 [−37.50, −4.37] mg, p = 0.01) between the spinal and general anesthesia groups. However, no significant differences were observed in the use of ephedrine (RR [95% CI] = 0.77 [0.19, 3.05]), blood loss (WMD [95%CI] = −34.38 [−89.56, 20.80) mL], myocardial infarction (RR [95% CI] = 0.78 [0.31, 1.94] mL), heart failure (RR [95% CI] = 0.87 [0.17, 4.36] mL), stroke (RR [95%CI) = 0.65 [0.22, 1.95] mL), postoperative nausea and vomiting (RR [95% CI] = 0.88 [0.17, 4.35] mL), delirium (RR [95% CI] = 1.08 [0.89, 1.31] mL), and mortality (RR [95% CI] = 1.10 [0.72, 1.68] mL) (all p

Abstract Posterolateral (PL)-depression fractures of the tibial plateau are difficult to manage. The aim of this study was: (1) to present our experience with a novel technique of robot-assisted percutaneous reduction and fixation and (2) to compare it with the traditional percutaneous screw osteosynthesis (PSO) technique for the treatment of PL-depression tibial plateau fractures. The clinical data of patients with PL-depression tibial plateau fractures treated by robot-assisted percutaneous reduction and fixation technique and traditional PSO technique from January 2017 to January 2021 were retrospectively analyzed. Among them, there were 18 cases in the robot-assisted group (RA group) and 23 cases in the PSO group. All fractures were unilateral, closed and fresh PL-depression fractures of the tibial plateau. Patients in the RA group were treated by robot assisted reduction and minimally invasive absorbable screw fixation. The PSO group was treated by closed reduction and percutaneous absorbable screw osteosynthesis. The incision length, operation time, intraoperative blood loss, fluoroscopic times, inpatient time, weight training time and postoperative complications of the two groups were statistically analyzed. The Rasmussen radiological score was used to assess the reduction quality after operation while the Rasmussen functional score was used to evaluate knee joint functions at one year postoperatively. All patients were followed for at least one year. There was no significant difference in demographic information between the two groups (p > 0.05). Compared with the PSO group, the RA group showed less fluoroscopic times and better Rasmussen radiological and functional scores (p 0.05). The novel robot-assisted percutaneous reduction and fixation technique had the characteristics of less radiation, accurate reduction and fixation. It could accelerate the rehabilitation of patients with PL-depression fractures of the tibial plateau and enable patients to obtain good joint functions.

Abstract CD8+ T cells are the executor in adaptive immune response, especially in anti-tumor immunity. They are the subset immune cells that are of high plasticity and multifunction. Their development, differentiation, activation and metabolism are delicately regulated by multiple factors. Stimuli from the internal and external environment could remodel CD8+ T cells, and correspondingly they will also make adjustments to the microenvironmental changes. Here we describe the most updated progresses in CD8+ T biology from transcriptional regulation to metabolism mechanisms, and also their interactions with the microenvironment, especially in cancer and immunotherapy. The expanding landscape of CD8+ T cell biology and discovery of potential targets to regulate CD8+ T cells will provide new viewpoints for clinical immunotherapy.

Abstract 3,5,6-trichloropyridinol (TCPY) is a metabolite of chlorpyrifos and chlorpyrifos-methyl, whose presence in the environment is of potential toxicity to human. So, it is need to monitor and regualte TCPY levels to protect human health. However, it is not known whether TCPY is associated with all-cause and cancer mortality and to which degree its levels contributed to hazard risk. The study enrolled 3951 participants from the National Health and Nutrition Examination Surveys (NHANES). Ultra-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry was used to measure urinary TCPY. Cox proportional hazards regression analysis was performed to explore the associations between TCPY and all-cause and cancer mortality. The study found that the average level of TCPY in the cohort was 1.79 μg/L and was higher in those who had passed away. Individuals in the highest quartile had a 1.56-fold independent increase in rate for all-cause mortality compared to those in the lowest quartile (hazard ratio [HR] 1.56, 95% confidence interval 1.09–2.24, p = 0.002). However, while the univariate model showed a hazard ratio of 2.37 (1.19–4.71) for the highest quartile in regards to cancer mortality, this association disappeared after adjusting for demographics, lifestyles, and comorbidities. Exposure to urinary 3,5,6-trichloropyridinol, as a result of insecticide exposure, increased the rate of all-cause mortality but was not independently associated with cancer mortality.

ObjectiveWe aimed to evaluate the efficacy of antibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation in the treatment of limb-localized osteomyelitis (Cierny–Mader type III) and analyze the causes and risk factors associated with infection recurrence.MethodsClinical data of 163 patients with localized osteomyelitis of the extremities treated with antibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation in Xi’an Honghui Hospital from January 2017 to December 2022 were retrospectively analyzed. All patients were diagnosed with localized osteomyelitis through clinical examination and treated with antibiotic-loaded calcium sulfate combined with autologous iliac bone. Based on the infection recurrence status, the patients were divided into the recurrence group and the non-recurrence group. The clinical data of the two groups were compared using univariate analysis. Subsequently, the distinct datasets were included in the binary logistic regression analysis to determine the risk and protective factors.ResultsThis study included 163 eligible patients, with an average age of 51.0 years (standard deviation: 14.9). After 12 months of follow-up, 25 patients (15.3%) experienced infection recurrence and were included in the recurrence group; the remaining 138 patients were included in the non-recurrence group. Among the 25 patients with recurrent infection, 20 required reoperation, four received antibiotic treatment alone, and one refused further treatment. Univariate analysis showed that education level, smoking, hypoproteinemia, open injury-related infection, and combined flap surgery were associated with infection recurrence (p < 0.05). Logistic regression analysis showed that open injury-related infection (odds ratio [OR] = 35.698; 95% confidence interval [CI]: 5.997–212.495; p < 0.001) and combined flap surgery (OR = 41.408; 95% CI: 5.806–295.343; p < 0.001) were independent risk factors for infection recurrence. Meanwhile, high education level (OR = 0.009; 95% CI: 0.001–0.061; p < 0.001) was a protective factor for infection recurrence.ConclusionAntibiotic-loaded calcium sulfate combined with autologous iliac bone transplantation is an effective method for treating limb-localized osteomyelitis. Patients without previous combined flap surgery and non-open injury-related infections have a relatively low probability of recurrence of infection after treatment with this surgical method. Additionally, patients with a history of smoking and hypoproteinemia should pay attention to preventing the recurrence of infection after operation. Providing additional guidance and support, particularly in patients with lower education levels and compliance, could contribute to the reduction of infection recurrence.

Background: The Proximal Femoral Nail Antirotation (PFNA) device is the most commonly used implant to fix unstable femoral trochanteric fractures (UFTFs), but it has a relatively high incidence of complications. Due to this factor, the modified intramedullary nail (MIN) was created to treat patients with UFTFs. The aim was to exhibit the MIN and make a comparison with PFNA and InterTAN using biomechanical methods. Methods: An adult UFTF model was developed using Mimics software. The PFNA, InterTAN nail, and MIN models were drawn referring to the corresponding parameters and installed in the fracture models. Vertical, anteroposterior (AP) bending, and torsion loads of the femoral head were set in advance and loaded onto the fracture models. The value of maximal displacement and von Mises stress was evaluated via finite element analysis (FEA). Results: The MIN model had smaller values for maximal displacement than that of the PFNA model, and the increase in displacement was less pronounced for the MIN compared to PFNA under increasing vertical loads. For the indicator of von Mises stress, the MIN model showed lower stress compared with the PFNA model in vertical loads ranging from 300 N to 2100 N. Except for the maximal stress at implants under AP bending loads, the MIN demonstrated the most superior biomechanical properties under AP bending and torsional loads. Conclusion: The MIN offered obvious advantages in terms of mechanical stability and stress distribution among the three studied implants, providing a promising implant option for patients with UFTFs.

ObjectiveTo compare the effects of allogeneic tendon coracoclavicular ligament reconstruction combined with Kirschner wire fixation and clavicular hook plate fixation on early postoperative pain, postoperative shoulder joint function score and shoulder joint mobility in patients with acromioclavicular joint dislocation.MethodsFrom January 2020 to January 2023, 43 patients with acromioclavicular joint dislocation admitted to Xi ‘an Honghui Hospital were included. Among them, 24 patients were treated with the clavicular hook plate technique (Hook Plate,HP) group, and 19 patients were treated with allogeneic tendon coracoclavicular ligament reconstruction combined with the Kirschner wire technique (Allogeneic Tendon, AT) group. The Constant-Murley score of shoulder joint function 6 months after operation, postoperative shoulder joint activity, preoperative and postoperative pain, operation time, intraoperative blood loss and complications were compared between the two groups.ResultsAll 43 patients were followed up for an average of 9.7 (9–12) months. The intraoperative blood loss in the allogeneic tendon group was less than in the hook plate group. The Constant-Murley shoulder function score was higher than that in the hook plate group 6 months after the operation. The abduction and lifting activity was greater than that in the hook plate group. The visual analogue scale scores at 3 days and 14 days after operation were lower than those in the hook plate group. The difference was statistically significant (p < 0.001). There was 1 case (5.3%) of exudation around the Kirschner needle track in the allogeneic tendon reconstruction group, and 5 cases (20.8%) of complications in the hook plate group, including 1 case of internal fixation stimulation, 2 cases of acromion impingement syndrome, 1 case of acromioclavicular joint osteoarthritis, and 1 case of shoulder joint stiffness. The complication rate of the allogeneic tendon group was lower than that of the hook plate group.ConclusionThe clinical efficacy of allogeneic tendon coracoclavicular ligament reconstruction combined with Kirschner wire fixation in treating acromioclavicular joint dislocation (Rockwood type III-V) is better than hook plate internal fixation. The patients have less early postoperative pain and better recovery of shoulder joint function and shoulder joint mobility.

The T cell immunoglobulin and mucin-domain containing-3 (TIM-3) receptor has gained significant attention as a promising target for cancer immunotherapy. The inhibitory effect of T cells by TIM-3 is mediated through the interaction between TIM-3 and its ligands. Ligand-blocking anti-TIM-3 antibodies possess the potential to reactivate antigen-specific T cells and augment anti-tumor immunity. However, the precise ligand-receptor interactions disrupted by the administration of TIM-3 blocking Abs have yet to be fully elucidated. In this study, we have developed a panel of monoclonal antibodies targeting human TIM-3, namely MsT001, MsT065, MsT229, and MsT286. They exhibited high sensitivities (10 pg/mL) and affinities (3.70 × 10−9 to 4.61 × 10−11 M) for TIM-3. The TIM-3 antibodies recognized distinct epitopes, including linear epitopes (MsT001 and MsT065), and a conformational epitope (MsT229 and MsT286). Additionally, the MsT229 and MsT286 displayed reactivity towards cynomolgus TIM-3. The interactions between TIM-3/Gal-9, TIM-3/HMGB-1, and TIM-3/CEACAM-1 disrupt the binding of MsT229 and MsT286, while leaving the binding of MsT001 and MsT065 unaffected. The inhibitory effect on the interaction between Gal-9 and TIM-3 was found to be dose-dependently in the presence of either MsT229 or MsT286. The findings suggested that the involvement of conformational epitopes in TIM-3 is crucial for its interaction with ligands, and we successfully generated novel anti-TIM-3 Abs that exhibit inhibitory potential. In conclusion, our finding offers valuable insights -on the comprehension and targeting of human TIM-3.

Respiratory tract infections constitute a significant global public health concern, accounting for around 20 % of child fatalities worldwide. Modulating the gut microbiota have the potential to serve as a promising strategy for both the prevention and treatment of respiratory infections. According to our prior research, the consumption of Bifidobacterium lactis Probio-M8 can notably enhance symptoms associated with respiratory tract infections in infants and young children. The current study is a follow-up work aimed at exploring the functional role of the gut microbes in the observed beneficial effects. We analyzed the fecal metagenomes of patients in both the probiotic group (n = 50) and the placebo group (n = 49). The results showed that Probio-M8 intervention may regulate the host inflammatory response by regulating the balance of intestinal microorganisms, bioactive metabolites and related pathways. Provides new insights into the study of probiotics in alleviating diseases related to the gut-lung axis.

Abstract The bootstrap approach (demanding consistency conditions to scattering amplitudes) has shown to be quite powerful to tightly constrain gauge theories at large N c . We extend previous analysis to scattering amplitudes involving pions and external gauge bosons. These amplitudes allow us to access the chiral anomaly and connect low-energy physical quantities to UV properties of the theory. In particular, we are able to obtain an analytic bound on the chiral anomaly coefficient as a function of the pion dipole polarizabilities. This bound can be useful for holographic models whose dual UV completions are not known, and provide a consistency condition to lattice simulations.

In this work, Er–Zr-Sc modified Al–Mg alloy, manufactured by selective laser melting, offers excellent mechanical properties, due to the formation of a desirable microstructure and the synergistic effects of multiple strengthening mechanisms. The microstructure in as-built and aged alloys have been characterized by scanning electron microscopy and transmission electron microscopy. The results show that the microstructure of alloy is composed of equiaxed grains (∼0.7 μm in diameter) along the boundary of molten pool and columnar grains (∼1.46 μm in width) inside the molten pool. Al3(Sc,Zr) particles serve as nucleation sites to promote the nucleation of equiaxed grains, and Al3(Er,M) eutectic phases and other compounds at the grain boundaries inhibit grain growth, both of which greatly refine the grains and bring significant grain boundary strengthening and Orowan strengthening effect. During the aging process, coherent Al3(Er,Zr,Sc) nano-precipitates are dispersedly precipitated from the Al matrix, which plays a key role in improving the mechanical properties of the aged alloy, and then the alloy reaches a yield strength of 530 MPa, a tensile strength of up to 542 MPa, and an elongation of over 12 %. Under the combined addition of Er, Sc, and Zr, and the influence of multi-element interaction, the alloy has high-density secondary phases and extremely fine grains, which are the main sources of reinforcement.

Abstract Surgical management of posterolateral tibial plateau (PLTP) fractures is challenging. One reason for this challenge is the lack of suitable internal fixation devices. Our aim was to introduce a novel plate via the anterolateral approach for managing PLTP fractures. The biomechanical testing and finite element analysis (FEA) were performed. PLTP fracture models were created using synthetic tibias (n = 10 within each group). These models were randomly assigned to three groups (groups A-C) and fixed with the lateral locking plate, the posterior buttress plate, and the novel plate, respectively. The vertical displacement of the posterolateral fragments was evaluated using biomechanical testing and FEA under axial loads of 250 N, 500 N, and 750 N. We also evaluated the stress distribution and maximum stress of each fracture model using FEA. Biomechanically, under the same loads of 250 N, 500 N, or 750 N, the vertical displacement was significantly different among the three fixation groups (p ≤ 0.001). FEA data indicated that the maximum displacement from group A to C was 3.58 mm, 3.23 mm, and 2.78 mm at 750 N, respectively. The maximum stress from group A to C was 220.88 MPa, 194.63 MPa, and 156.77 MPa in implants, and 62.02 MPa, 77.71 MPa, and 54.15 MPa in bones at 750 N, respectively. The general trends at 250 N and 500 N were consistent with those at 750 N. Based on our biomechanical and FEA results, the novel plate could be a good option for treating PLTP fractures. The novel plate showed stable and reliable features, indicating its suitability for further clinical application.

Abstract Glioblastoma multiforme (GBM) is a highly vascularized malignant cancer of the central nervous system, and the presence of vasculogenic mimicry (VM) severely limits the effectiveness of anti-vascular therapy. In this study, we identified downregulated circHECTD1, which acted as a key VM-suppressed factor in GBM. circHECTD1 elevation significantly inhibited cell proliferation, migration, invasion and tube-like structure formation in GBM. RIP assay was used to demonstrate that the flanking intron sequence of circHECTD1 can be specifically bound by RBMS3, thereby inducing circHECTD1 formation to regulate VM formation in GBM. circHECTD1 was confirmed to possess a strong protein-encoding capacity and the encoded functional peptide 463aa was identified by LC-MS/MS. Both circHECTD1 and 463aa significantly inhibited GBM VM formation in vivo and in vitro. Analysis of the 463aa protein sequence revealed that it contained a ubiquitination-related domain and promoted NR2F1 degradation by regulating the ubiquitination of the NR2F1 at K396. ChIP assay verified that NR2F1 could directly bind to the promoter region of MMP2, MMP9 and VE-cadherin, transcriptionally promoting the expression of VM-related proteins, which in turn enhanced VM formation in GBM. In summary, we clarified a novel pathway for RBMS3-induced circHECTD1 encoding functional peptide 463aa to mediate the ubiquitination of NR2F1, which inhibited VM formation in GBM. This study aimed to reveal new mechanisms of GBM progression in order to provide novel approaches and strategies for the anti-vascular therapy of GBM. The schematic illustration showed the inhibitory effect of circHECTD1-463aa in the VM formation in GBM.

Lysine succinylation is a naturally occurring post-translational modification (PTM) that regulates the stability and function of proteins. It can be regulated by enzymes such as SIRT5 and SIRT7. Recently, the effect and significance of lysine succinylation in cancer and its implication in immunity have been extensively explored. Lysine succinylation is involved in the malignant phenotype of cancer cells. Abnormal regulation of lysine succinylation occurs in different cancers, and inhibitors targeting lysine succinylation regulatory enzymes can be used as potential anti-cancer strategies. Therefore, this review focused on the target protein lysine succinylation and its functions in cancer and immunity, in order to provide a reference for finding more potential clinical cancer targets in the future.

Abstract Ignition advance angle is one of the important factors affecting the performance of the engine, when it occurs abnormally will make the engine power and economy worse, and even cause serious damage to the engine. Therefore, it is very necessary to recognize the abnormal ignition advance angle of the engine. However, the engine system is closed and has a complex structure, which makes traditional diagnostic methods difficult. This paper proposes an intelligent identification method based on acoustic emission (AE) signals, which collects the AE signals from the engine surface and divides their spectra into equal parts, and selects the frequency bands with high contribution to the classification based on the minimum distance method to construct feature maps, which is used as the input to the convolutional neural network (CNN). The extracted frequency band features of this method can better characterize the AE signals, and the constructed feature maps make the fault information more obvious. Experiments show that the accuracy of this method for abnormal ignition advance angle under normal operating conditions of piston aero-engine is 100%, which is better than the traditional methods. In addition, the recognition accuracies under the other two operating conditions are 99.75% and 98.5%, respectively, indicating that the method has a certain universality.

Abstract Background Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) exhibit the potential to repair the injured heart after myocardial infarction (MI) by promoting neovascularization and cardiomyocyte survival. However, because of the low cellular retention and poor engraftment efficacy, cell therapy of MI is partly mediated by exosomes secreted from the transplanted cells. In this study, we investigated whether exosomes secreted from hiPSC-ECs could become a promising acellular approach to repair the infarcted heart after MI and elucidated the underlying protective mechanism. Methods The hiPSC-ECs were differentiated, and exosomes were isolated in vitro. Then, hiPSC-EC exosomes were delivered by intramyocardial injection in a murine MI model in vivo. Echocardiography, combined with hemodynamic measurement, histological examination, Ca2+ transient and cell shortening assessment, and Western blot, was used to determine the protective effects of hiPSC-EC exosomes on the infarcted heart. Furthermore, microRNA sequencing, luciferase activity assay, and microRNA gain–loss function experiments were performed to investigate the enriched microRNA and its role in exosome-mediated effects. Results In vitro, the hiPSC-EC exosomes enhanced intracellular Ca2+ transients, increased ATP content, and improved cell survival to protect cardiomyocytes from oxygen–glucose deprivation injury. Congruously, hiPSC-EC exosome administration in vivo improved the myocardial contractile function and attenuated the harmful left ventricular remodeling after MI without increasing the frequency of arrhythmias. Mechanistically, the hiPSC-EC exosomes notably rescued the protein expression and function of the sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA-2a) and ryanodine receptor 2 (RyR-2) to maintain intracellular Ca2+ homeostasis and increase cardiomyocyte contraction after MI. The microRNA sequencing showed that miR-100-5p was the most abundant microRNA in exosomes. miR-100-5p could target protein phosphatase 1β (PP-1β) to enhance phospholamban (PLB) phosphorylation at Ser16 and subsequent SERCA activity, which contributes to the hiPSC-EC exosome-exerted cytoprotective effects on maintaining intracellular Ca2+ homeostasis and promoting cardiomyocyte survival. Conclusion The hiPSC-EC exosomes maintain cardiomyocyte Ca2+ homeostasis to improve myocardial recovery after MI, which may provide an acellular therapeutic option for myocardial injury.

Abstract The rural energy transition is critical in China’s efforts to achieve carbon neutrality and improve air quality. However, the costs and health benefits associated with the transition to carbon neutrality remain unclear. Here we explore the cost-effective transition pathways and air quality-related health impacts using an integrated energy-air quality-health modeling framework. We find that decarbonizing rural cooking and heating would triple contemporary energy consumption from 2014 to 2060, considerably reducing energy poverty nationwide. By 2060, electric cooking ranges and air-to-air heat pumps should be widely integrated, costing an additional 13 billion USD nationally in transformation costs, with ~40% concentrated in Shandong, Heilongjiang, Shanxi and Hebei provinces. Rural residential decarbonization would remarkably improve air quality in northern China, yielding substantial health co-benefits. Notably, monetized health benefits in most provinces are projected to offset transformation costs, except for certain relatively lower-development southwestern provinces, implying more financial support for rural residents in these areas will be needed.

Abstract Constipation and systemic inflammation are common in late pregnant and lactating sows, which cause health problems like uteritis, mastitis, dystocia, or even stillbirth, further influencing piglets’ survival and growth. Probiotic supplementation can improve such issues, but the beneficial mechanism of relieving constipation and enhancing gut motility remains underexplored. This study aimed to investigate the effects and mechanism of probiotic supplementation in drinking water to late pregnant sows on constipation, inflammation, and piglets’ growth performance. Seventy-four sows were randomly allocated to probiotic (n = 36) and control (n = 38) groups. Probiotic treatment significantly relieved sow constipation, enhanced serum IL-4 and IL-10 levels while reducing serum IL-1β, IL-12p40, and TNF-α levels, and increased piglet daily gain and weaning weight. Furthermore, probiotic administration reshaped the sow gut bacteriome and phageome structure/diversity, accompanied by increases in some potentially beneficial bacteria. At 113 days of gestation, the probiotic group was enriched in several gut microbial bioactive metabolites, multiple carbohydrate-active enzymes that degrade pectin and starch, fecal butyrate and acetate, and some serum metabolites involved in vitamin and amino acid metabolism. Our integrated correlation network analysis revealed that the alleviation of constipation and inflammation was associated with changes in the sow gut bacteriome, phageome, bioactive metabolic potential, and metabolism.

Abstract We present the explicit construction of the effective field theory (EFT) of standard model mass eigenstates. The EFT, which is invariant under U(1)e.m. × SU(3) c , is constructed based on the on-shell method and Young Tableau technique. This EFT serves as a new formulation of the Higgs EFT (HEFT), which can describe the infrared effects of new physics at the electroweak symmetry-breaking phase with greater conciseness. The current HEFT operator basis has a clear physical interpretation, making it more accessible for research in phenomenology. A complete list of HEFT operator bases for any-point vertices up to any dimension could be provided, and three- and four-point bases are provided as examples. Additionally, this framework realized as Mathematica program can be used to construct the EFT of any type of dark matter or particles with any spin.

Providing higher precision Direction of Arrival (DOA) estimation has become a hot topic in the field of array signal processing for parameter estimation in recent years. However, when the physical aperture of the actual array is small, its aperture limitation means that even with super-resolution estimation algorithms, the achievable estimation precision is limited. This paper takes a novel approach by constructing an optimization algorithm using the covariance fitting criterion based on the array output’s covariance matrix to fit and obtain the covariance matrix of a large aperture virtual array, thereby providing high-precision angular resolution through virtual aperture expansion. The covariance fitting expansion analysis and discussion are unfolded for both uniform linear arrays (ULAs) and sparse linear arrays (SLAs) under four different scenarios. Theoretical analysis and simulation experiments demonstrate that these methods can enhance the effective performance of angle estimation, especially in low signal-to-noise ratios (SNRs) and at small angular intervals by fitting virtual extended aperture data.

Underwater terrain-aided navigation (TAN) can obtain high-precision positioning independently and autonomously under the conditions of a communication rejection space, which is an important breakthrough for the autonomous and refined operation of deep-sea autonomous underwater vehicles near the seabed. Although TAN originated in the aviation field, the particularity of the underwater physical environment has led to the formation of a different theoretical and technical system. In this article, the application background, operating principles, and most important technical aspects of underwater TAN are introduced. Then, the relevant algorithms involved in the two main modules (the terrain-aided positioning module and the iterative filtering estimation module) of the underwater TAN are reviewed. Finally, other cutting-edge issues in the field of underwater TAN are summarized. The purpose of this article is to provide researchers with a comprehensive understanding of the current research status and possible future developments in the TAN field.

Preventing eutrophication requires a deep understanding of nutrient sources and migration processes. The Guanshan River in the Danjiangkou Reservoir was selected as a typical agricultural basin. River water, sediment, and soil samples were collected to determine nitrogen (N) and phosphorus (P) contents and forms. Multivariate statistical analysis, buffer analysis, and extreme gradient boosting regression (XGBoost) were used to investigate the nutrient sources, the sources’ scale effects, and migration. The results showed that the exogenous sources of river nutrients were fertilizer (provided phosphate (PO4-P) and ammonium (NH4-N)), domestic wastewater (provided nitrate (NO3-N) and organic nitrogen), and natural soil and rock leaching (provided PO4-P and organic phosphorus). Fertilization within 300–1200 m and domestic wastewater discharge within 150 m of the river affected the contents of the river nutrients significantly (with R ranging between 0.40 and 0.73, p ≤ 0.01). The sediment was the N source and P sink of the overlying water. With NH4-N/PO4-P compound fertilization, the NO3-N and calcium-bound phosphorus (Ca-P) exhibited co-enrichment. Appropriately increasing NH4-N application could stimulate P biological uptake, thus inhibiting P emigration from agricultural soil under N-limited states. In conclusion, this study effectively recognized river nutrient sources and their scale impacts and also explored more effective fertilization strategies, which are beneficial for the optimized management of agricultural activities.