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Abstract Waste activated sludge (WAS) is attracting attention for its energy and resource potential. Anaerobic digestion (AD) can be used to efficiently recover energy resources and stabilize pollutants in WAS, with biochar emerging as an ideal additive to boost this process. However, the low abundance of surface functional groups and small pore structure of raw biochar may limit its performance in the AD of WAS. These limitations can be overcome by using functional biochar. In this review, the preparation and modification methods for functional biochar and its role in the AD of WAS are systematically summarized and discussed. Notably, the role of functional biochar in electron transfer, buffering effects, microbial immobilization, alleviation of inhibitory effects, and functional microbial modulation are analyzed. Additionally, the impacts of biochar on digestate utilization, pollutant removal, and carbon fixation are discussed. Special attention is given to functional biochar for its ability to promote circular economy and carbon neutrality. Finally, future perspectives on the use of functional biochar in the AD of WAS are presented. The aim of this review is to provide insights into the application of functional biochar in the AD of WAS from the perspective of performance improvement, resource utilization, and circular economy. Graphical Abstract

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. Method Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. Result Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P

Abstract Aims We aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF). Methods and results The study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event‐free survival was determined by Kaplan–Meier curves and differences in survival were assessed using log‐rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver‐operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P

In response to the development of the concepts of “carbon neutrality” and “carbon peak”, it is critical to developing materials with high near-infrared (NIR) solar reflectivity and high emissivity in the atmospheric transparency window (ATW; 8–13 μm) to advance zero energy consumption radiative cooling technology. To regulate emission and reflection properties, a series of high-entropy rare earth stannate ceramics (HE-RE2Sn2O7: (Y0.2La0.2Nd0.2Eu0.2Gd0.2)2Sn2O7, (Y0.2La0.2Sm0.2Eu0.2Lu0.2)2Sn2O7, and (Y0.2La0.2Gd0.2Yb0.2Lu0.2)2Sn2O7) with severe lattice distortion were prepared using a solid phase reaction followed by a pressureless sintering method for the first time. Lattice distortion is accomplished by introducing rare earth elements with different cation radii and mass. The as-synthesized HE-RE2Sn2O7 ceramics possess high ATW emissivity (91.38%–95.41%), high NIR solar reflectivity (92.74%–97.62%), low thermal conductivity (1.080–1.619 W·m−1·K−1), and excellent chemical stability. On the one hand, the lattice distortion intensifies the asymmetry of the structural unit to cause a notable alteration in the electric dipole moment, ultimately enlarging the ATW emissivity. On the other hand, by selecting difficult excitation elements, HE-RE2Sn2O7, which has a wide band gap (Eg), exhibits high NIR solar reflectivity. Hence, the multi-component design can effectively enhance radiative cooling ability of HE-RE2Sn2O7 and provide a novel strategy for developing radiative cooling materials.

The proven geological reserves of the Shenfu deep coalbed methane (CBM) field on the eastern margin of the Ordos Basin exceed 100 billion cubic meters. It is of great significance to realizing the efficient development of deep CBM in this region to ensure the national energy supply. However, the complexity of the geological environment which includes high stress, medium-high temperatures, low permeability, strong heterogeneity, and wide developed cleats and natural fractures, makes it challenging for the existed shallow and medium CBM fracturing techniques to be fully applicable to deep CBM resources. As a result, the stimulation scale and parameters for deep coalbed fracturing are still in the trial-and-error stage. In order to explore the stimulation techniques which are compatible with the geological conditions of deep coalbeds, the Shenfu block in the Ordos Basin was taken as the geological background and the large-scale hydraulic fracturing of deep coal seams was conducted as an engineering practice. The authors designed the idea of “Push the limit to the beyond + balanced propagation + effective support”, and proposed the massive hydraulic fracturing techniques based on “multi-stage multi-clusters with moderate-dense cutting + perforation with equal apertures, deep penetration and limited flow + integrated variable viscosity (rock breaking by higher viscous slick water + complex fracture network generating by lower viscous slick water) + high pumping rate with high proppant concentration + pre-acid treatment to reduce the breakdown pressure + graded proppants with multiple sizes to support fractures”. Then, the authors put forward an integrated “Geology-Engineering-AI” workflow to perform post-frac analysis, through double matching and correcting the fracturing pumping pressure and production rate automatically, accurately characterized the stimulated reservoir volume (SRV) and drained rock volume (DRV), and predicted the estimated ultimate recovery (EUR) under different fracturing scales and well types. Finally, by statistically analyzing the gas production characteristics of multiple wells in the Shenfu block and utilizing the random forest method, the primary controlling factors affecting the production capacity of deep CBM were quantitatively analyzed. The results demonstrate that after reservoir stimulation, directional wells can achieve a maximum daily gas production rate exceeding 10 000 m3/d, while horizontal wells can achieve a maximum daily gas production rate exceeding 20 000 m3/d. It indicates that the deep coal beds have good fracturing properties and great development potential. The primary impact factors for peak gas production rate are gas content, coalbed thickness and proppant concentration, while the major impact factors for cumulative gas production include gas content, proppant concentration, and total volume of proppants.

Abstract Assessing the genetic structure of local varieties and understanding their genetic data are crucial for effective management and preservation. However, the genetic differences among local breeds require further explanation. To enhance our understanding of their population structure and genetic diversity, we conducted a genome-wide comparative study of Chaohu and Ji’an Red ducks using genome sequence and restriction site-associated DNA sequencing technology. Our analysis revealed a distinct genetic distinction between the two breeds, leading to divided groups. The phylogenetic tree for Chaohu duck displayed two branches, potentially indicating minimal impact from artificial selection. Additionally, our ROH (runs of homozygosity) analysis revealed that Chaohu ducks had a lower average inbreeding coefficient than Ji’an Red ducks. We identified several genomic regions with high genetic similarity in these indigenous duck breeds. By conducting a selective sweep analysis, we identified 574 candidate genes associated with muscle growth (BMP2, ITGA8, MYLK, and PTCH1), fat deposits (ELOVL1 and HACD2), and pigmentation (ASIP and LOC101797494). These results offer valuable insights for the further enhancement and conservation of Chinese indigenous duck breeds.

Abstract Background HIV self-testing (HIVST) was recommended to improve HIV testing services. China initiated some of the first HIVST pilots in the world, providing a unique opportunity for implementation research. We aim to investigate HIVST adoption and its following linkage to care among Chinese men who have sex with men (MSM). Methods Data were collected using an online questionnaire distributed on major social media platforms in 2018, one year after HIVST was officially endorsed and allowed for sale. MSM who were at least 16 years old, assigned as male at birth, and ever tested for HIV were eligible. Primary outcome, adoption was defined as ever use of HIVST. Bivariate and multivariable logistic regressions were performed to explore the association between HIVST adoption and sociodemographic and behavioral factors. Linkage to care was also described via the following sequential events as indicators: (1) receiving result after recent test (2), seeking care from healthcare facility if test result was positive or indeterminate, and (3) delayed time before seeking care. Results A total of 540 participants were included with an average age of 27.4 ± 6.6. Most were never married (87.4%) and half completed college (52.2%). Overall, 75.2% had adopted HIVST. Self-test kits were commonly obtained from community-based organizations (54.4%) and from online (46.6%). HIVST adoption was positively associated with having college or higher education (OR = 1.66, 95%CI: 1.07–2.57), and negatively associated with age older than 30 (AOR = 0.52, 95%CI: 0.32–0.84). Adoption was not associated with other socio-demographic or behavioral factors. After receiving HIV-positive or indeterminate results, 25/25 of HIVST adopters sought care while 3 out of 7 (42.9%) non-adopters sought care (p

Abstract Multiple gene abnormalities are major drivers of tumorigenesis. NF-κB p65 overactivation and cGAS silencing are important triggers and genetic defects that accelerate tumorigenesis. However, the simultaneous correction of NF-κB p65 and cGAS abnormalities remains to be further explored. Here, we propose a novel Induced Dual-Target Rebalance (IDTR) strategy for simultaneously correcting defects in cGAS and NF-κB p65. By using our IDTR approach, we showed for the first time that oncolytic adenovirus H101 could reactivate silenced cGAS, while silencing GAU1 long noncoding RNA (lncRNA) inhibited NF-κB p65 overactivation, resulting in efficient in vitro and in vivo antitumor efficacy in colorectal tumors. Intriguingly, we further demonstrated that oncolytic adenoviruses reactivated cGAS by promoting H3K4 trimethylation of the cGAS promoter. In addition, silencing GAU1 using antisense oligonucleotides significantly reduced H3K27 acetylation at the NF-κB p65 promoter and inhibited NF-κB p65 transcription. Our study revealed an aberrant therapeutic mechanism underlying two tumor defects, cGAS and NF-κB p65, and provided an alternative IDTR approach based on oncolytic adenovirus and antisense oligonucleotides for efficient therapeutic efficacy in tumors.

Abstract Previous reports have established that rESWT fosters angiogenesis, yet the mechanism by which rESWT promotes cerebral angiogenesis remains elusive. rESWT stimulated HUVECs proliferation as evidenced by the CCK-8 test, with an optimal dosage of 2.0 Bar, 200 impulses, and 2 Hz. The tube formation assay of HUVECs revealed that tube formation peaked at 36 h post-rESWT treatment, concurrent with the lowest expression level of Bach1, as detected by both Western blot and immunofluorescence. The expression level of Wnt3a, β-catenin, and VEGF also peaked at 36 h. A Bach1 overexpression plasmid was transfected into HUVECs, resulting in a decreased expression level of Wnt3a, β-catenin, and VEGF. Upon treatment with rESWT, the down-regulation of Wnt3a, β-catenin, and VEGF expression in the transfected cells was reversed. The Wnt/β-catenin inhibitor DKK-1 was utilized to suppress Wnt3a and β-catenin expression, which led to a concurrent decrease in VEGF expression. However, rESWT treatment could restore the expression of these three proteins, even in the presence of DKK-1. Moreover, in the established OGD model, it was observed that rESWT could inhibit the overexpression of Bach1 and enhance VEGF and VEGFR-2 expression under the OGD environment.

Abstract In rural China, the aging population faces unique challenges that affect their life satisfaction. These challenges are compounded by disparities in access to resources compared to urban areas, making it crucial to address these issues to ensure a dignified and fulfilling later life. Understanding and improving life satisfaction for this demographic is essential, not only for the well-being of the elderly but also for the overall social stability and economic sustainability of these communities. Using a rural sample from the Chinese Social Survey (CSS), this study investigates the interplay between social quality factors and life satisfaction among older adults in rural China. It focuses on the roles of socioeconomic security, social cohesion, social inclusion, and social empowerment in shaping the well-being of this demographic. It was found that the four conditional factors of social quality—socioeconomic security, social cohesion, social inclusion, and social empowerment—have different influences on life satisfaction among older adults in rural areas. The statistical model shows that the influence of absolute family income on social and economic security does not have statistical significance. In contrast, housing, pension insurance participation, and public safety perception positively affect life satisfaction among older adults in rural areas. Among the social cohesion factors, higher social morality, legal system evaluation, social identity, grassroots government, and interpersonal trust contribute to the life satisfaction of older adults in rural areas. Regarding social inclusion factors, good social tolerance, social equity, and perception of government public services can significantly improve life satisfaction among older adults in rural areas. For social empowerment factors, social participation helps expand the social support network of older adults in rural areas, enhancing their life satisfaction. Paths to improving the quality of rural society should be explored to improve relative poverty in rural areas. They should continue to be pursued to strengthen the old-age security system for older adults in rural areas. Further, the National Medium- and Long-Term Plan for Actively Responding to Population Aging should be the base for forming an elderly-friendly society. A good atmosphere promotes the participation of people, families, and society; supports social cohesion; enhances inclusion; and promotes social participation, improving life satisfaction.

Abstract Nano-switch structures are important control elements in nanoelectromechanical systems and have potential applications in future nanodevices. This paper analyzes the effects of surface effects, geometric nonlinearity, electrostatic forces, and intermolecular forces on the nonlinear bending behavior and adhesion stability of nano-switches. Based on the Von Karman geometric nonlinearity theory, four types of boundary conditions for the nano-switch structure were specifically calculated. The results show that surface effects have a significant impact on the nonlinear bending and adhesion stability of nano-switches. Surface effects increase the adhesion voltage of the nano-switch and decrease its adhesion displacement, and as the size of the nano-switch structure increases, the impact of surface effects decreases. A comparative analysis of the linear theory and the nonlinear theory results shows that the adhesion voltage predicted by the linear theory is smaller than that predicted by the nonlinear theory. The effect of geometric nonlinearity increases as the size of the nano-switch structure increases, as the distance between the electrodes increases, and as the aspect ratio of the nano-switch structure increases. These findings provide theoretical support and reference for the design and use of future nanodevices and nanoelectromechanical systems.

Ultra-fine grained magnesium alloys are usually prepared by severe deformation and medium-low temperature deformation. In this work, it has been found that the binary Mg-1.2Ce alloy with the uniform distributed Mg12Ce precipitates smaller than 3 μm is a good candidate to obtain ultra-fine grains by conventional one-step extrusion at high temperatures. All the three Mg-1.2Ce samples extruded at 300 °C, 350 °C and 400 °C show a bimodal microstructure with high-density dislocations, whose average grain sizes are 1.19 ± 0.92 μm, 1.32 ± 1.30 μm, and 1.44 ± 1.33 μm, respectively. A linear relation of ln(d) = -0.05ln(Z)+1.27 was determined relating the average grain size (d) to the Zener-Hollomon parameter (Z). The alloy extruded at 300 °C exhibits an exceptionally high ultimate tensile strength (UTS) of 412.3 ± 5.3 MPa and yield strength (TYS) of 387.6 ± 3.2 MPa, but a low elongation after fracture (El) of 4.9 ± 0.8 %. With the extrusion temperature increasing, the tensile strength gradually decreases. For the 1.2E-400 sample, the TYS and the UTS drop to 347.2 ± 2.1 MPa and 349.4 ± 2.8 MPa, while the El increases to a more acceptable value of 12.6 ± 1.4 %. The microstructure analysis reveals that Ce atoms segregate along grain boundaries and dislocations in the Mg-1.2Ce alloy, which can limit the gliding of GBs or the slipping and climbing of dislocations. Additionally, dislocations can be pinned by Mg12Ce precipitates, thereby also restricting dislocation and grain boundary mobility. Consequently, the dynamic recrystallization (DRX) process is delayed, leading to the formation of a bimodal microstructure.

Abstract Dynamin-related protein 1 (Drp1) is a crucial regulator of mitochondrial dynamics, the overactivation of which can lead to cardiovascular disease. Multiple distinct posttranscriptional modifications of Drp1 have been reported, among which S-nitrosylation was recently introduced. However, the detailed regulatory mechanism of S-nitrosylation of Drp1 (SNO-Drp1) in cardiac microvascular dysfunction in diabetes remains elusive. The present study revealed that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was consistently upregulated in diabetic cardiomyopathy (DCM) and promoted SNO-Drp1 in cardiac microvascular endothelial cells (CMECs), which in turn led to mitochondrial dysfunction and cardiac microvascular disorder. Further studies confirmed that MAP4K4 promoted SNO-Drp1 at human C644 (mouse C650) by inhibiting glutathione peroxidase 4 (GPX4) expression, through which MAP4K4 stimulated endothelial ferroptosis in diabetes. In contrast, inhibition of MAP4K4 via DMX-5804 significantly reduced endothelial ferroptosis, alleviated cardiac microvascular dysfunction and improved cardiac dysfunction in db/db mice by reducing SNO-Drp1. In parallel, the C650A mutation in mice abolished SNO-Drp1 and the role of Drp1 in promoting cardiac microvascular disorder and cardiac dysfunction. In conclusion, our findings demonstrate that MAP4K4 plays an important role in endothelial dysfunction in DCM and reveal that SNO-Drp1 and ferroptosis activation may act as downstream targets, representing potential therapeutic targets for DCM.

Abstract Background This study aims to investigate the influencing factors of vascular calcification in peritoneal dialysis (PD) patients and its relationship with long-term prognosis. Methods This retrospective cohort study included chronic kidney disease patients undergoing peritoneal dialysis at the Peritoneal Dialysis Center of Beijing Luhu Hospital, Capital Medical University, from January 2019 to March 2019. Demographic and clinical laboratory data, including serum sclerostin (SOST), calcium (Ca), phosphate (P), serum albumin (ALB), and intact parathyroid hormone (iPTH) levels, were collected. Abdominal aortic calcification (AAC) was assessed using abdominal lateral X-ray examination to determine the occurrence of vascular calcification, and patients were divided into the AAC group and Non-AAC group based on the results. Results A total of 91 patients were included in the study. The AAC group consisted of 46 patients, while the Non-AAC group consisted of 45 patients. The AAC group had significantly older patients compared to the non-AAC group (P

Abstract The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, an important component of the innate immune system, is involved in the development of several diseases. Ectopic DNA-induced inflammatory responses are involved in several pathological processes. Repeated damage to tissues and metabolic organelles releases a large number of damage-associated molecular patterns (mitochondrial DNA, nuclear DNA, and exogenous DNA). The DNA fragments released into the cytoplasm are sensed by the sensor cGAS to initiate immune responses through the bridging protein STING. Many recent studies have revealed a regulatory role of the cGAS-STING signaling pathway in cardiovascular diseases (CVDs) such as myocardial infarction, heart failure, atherosclerosis, and aortic dissection/aneurysm. Furthermore, increasing evidence suggests that inhibiting the cGAS-STING signaling pathway can significantly inhibit myocardial hypertrophy and inflammatory cell infiltration. Therefore, this review is intended to identify risk factors for activating the cGAS-STING pathway to reduce risks and to simultaneously further elucidate the biological function of this pathway in the cardiovascular field, as well as its potential as a therapeutic target.

Abstract Herein, the feasibility of artificial black soil (ABS) derived from hydrothermal humification-hydrothermal carbonization (HTH-HTC) for restructuration of weak soil was verified. This study breaks through the long history of soil formation and evolution, and obtains reconstructed anthropogenic soil (AS) system which only takes one month, for the further application of rice seedlings. HTH-HTC derived by-products are slightly acidic, which facilitates the effective nutrient uptake and prevention of wilt diseases for acid-loving rice seedlings. AS mainly consists of the inherent components retained from weak soil such as SiO2 and minerals, and exogenous components such as artificial humic substances and hydrochar, as introduced by hydrothermal humification processes. Results exhibit that AS has high contents of ammonium nitrogen, organic matter, organic carbon, and abundant porous structure for nutrient transport and water holding, especially, the community diversity and richness of microbial system gets the expected recovery and new beneficial bacteria (such as Caballeronia calidae) or fungi (such as Humicola) appear. Positive effects of AS on agronomic traits in rice seedlings are quantified. As a general result, this study supports the application of AS in sustainable agriculture, and provides a novel strategy to tackle the already-omnipresent land degradation by anthropogenic misuse and larger scale accidents.

Background/Aims Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. Methods Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. Results The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. Conclusions For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.

Abstract Inflammation and fibrosis often occur in the kidney after acute injury, resulting in chronic kidney disease and consequent renal failure. Recent studies have indicated that lymphangiogenesis can drive renal inflammation and fibrosis in injured kidneys. However, whether and how this pathogenesis affects the contralateral kidney remain largely unknown. In our study, we uncovered a mechanism by which the contralateral kidney responded to injury. We found that the activation of mineralocorticoid receptors and the increase in vascular endothelial growth factor C in the contralateral kidney after unilateral ureteral obstruction could promote lymphangiogenesis. Furthermore, mineralocorticoid receptor activation in lymphatic endothelial cells resulted in the secretion of myofibroblast markers, thereby contributing to renal fibrosis. We observed that this process could be attenuated by administering the mineralocorticoid receptor blocker eplerenone, which, prevented the development of fibrotic injury in the contralateral kidneys of rats with unilateral ureteral obstruction. These findings offer valuable insights into the intricate mechanisms underlying kidney injury and may have implications for the development of therapeutic strategies to mitigate renal fibrosis in the context of kidney disease.

Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive and fatal pediatric brain cancer. One pre-requisite for tumor cells to infiltrate is adhesion to extracellular matrix (ECM) components. However, it remains largely unknown which ECM proteins are critical in enabling DIPG adhesion and migration and which integrin receptors mediate these processes. Here, we identify laminin as a key ECM protein that supports robust DIPG cell adhesion and migration. To study DIPG infiltration, we developed a DIPG-neural assembloid model, which is composed of a DIPG spheroid fused to a human induced pluripotent stem cell-derived neural organoid. Using this assembloid model, we demonstrate that knockdown of laminin-associated integrins significantly impedes DIPG infiltration. Moreover, laminin-associated integrin knockdown improves DIPG response to radiation and HDAC inhibitor treatment within the DIPG-neural assembloids. These findings reveal the critical role of laminin-associated integrins in mediating DIPG progression and drug response. The results also provide evidence that disrupting integrin receptors may offer a novel therapeutic strategy to enhance DIPG treatment outcomes. Finally, these results establish DIPG-neural assembloid models as a powerful tool to study DIPG disease progression and enable drug discovery.

20CrMnTi steel is widely used in the gear manufacturing field of engineering machinery. The addition of Ti element to steel can effectively improve its low-temperature impact toughness and enhance its mechanical properties. However, during the smelting process of 20CrMnTi, large-sized TiN inclusions are inevitably formed in the steel, which affects its service performance improvement. This paper focuses on the directional modification behaviors of TiN inclusions in 20CrMnTi gear steel by rare earth Ce under deoxygenation conditions of Si–Ca–Ba alloy. The results show that under the deoxygenation conditions of Si–Ca–Ba alone, there are composite inclusions in 20CrMnTi steel with CaAl12O19 as the core and TiN wrapped around the periphery, all of which have sizes greater than 2 μm. This type of inclusion is square or diamond shaped, and the addition of Si–Ca–Ba deoxygenation alone has poor TiN modification effect on gear steel 20CrMnTi. Adding Ce element can effectively improve the nucleation core of inclusions. The CeAlO3–TiN and (CaAl12O19–Ba–Ce)–TiN composite inclusions are formed, and the TiN inclusions are modified in terms of morphology and size. The average size of inclusions decreases from 4.1 to 3.0 μm, which prevented the excessive growth of pure TiN inclusions to some extent.

Gas content is an important parameter for the prediction of coal and gas outburst risk, the estimation of coal seam gas resource, and the design of mine gas control engineering. Focusing on how to accurately and quickly determine the gas content of coal seams in large area, and relying on the National Science and Technology Major Project, the National Natural Science Foundation of China, the Joint Fund of Coal Enterprises and other projects to develop scientific and technological research, some progress had been made in sampling and testing, and the main manifestations were as follows. ① The development of sampling for gas content determination in coal seam has gone through four stages, namely, orifice sampling, core tube spot sampling, pressure injection spot sampling, and sealed sampling. The pressure holding capacity of the sealed sampling equipment reached 11.5 MPa, and the diameter of coal core reached 38 mm. ② According to different geological conditions of coal seams, three types of sampling techniques had been developed, including directional long borehole sealed sampling along coal seam, floor cross-layer borehole sealed sampling, and comb-shaped directional long borehole sealed sampling in roof or floor. ③ In the hard coal seams of Jiaozuo mining area in Henan Province and Jincheng mining area in Shanxi Province, the sampling depth of the directional long borehole along the seam reached 516 m, and the gas content of the coal seam measured by the sealed sampling method was increased by an average of 0.44 and 1.04 times compared with the conventional sampling method, respectively. In the broken soft coal seam of the Huainan mining area in Anhui Province, the sealed sampling depth of the cross-layer borehole reached 209 m, and the measured gas content of the coal seam was increased by 0.26 times on average compared with the conventional sampling method. In the broken soft coal seam of the Huaibei mining area in Anhui Province, the comb drilling sealed sampling depth reached 484 m in roof or floor, and the measured coal seam gas content was 0.19 times higher than that of the conventional sampling method. The sealed sampling method was superior than the conventional sampling method in terms of determination accuracy and detection range of coal seam gas content. ④ In terms of gas content testing, in addition to the traditional natural desorption test, a series of coal mine gas content rapid test equipment had been developed, which can measure the gas content of coal seam within 30 min at the earliest, and was generally used for gas content testing in 100-meter hole. It is proposed that the sealed sampling equipment for coal seam gas content determination needs to be developed in the direction of miniaturization and lightweight, and it can realize sealed sampling with the drilling. In the test, a reasonable desorption termination limit should be determined according to the actual situation, and the testing equipment and sealed sampling equipment should be further combined to achieve the rapid and accurate determination of gas content in deep hole. Sealed sampling technology has become the main means of accurate exploration and prediction of coal seam gas content in large areas, and it is an important technical guarantee for the safe and efficient coal mining.

Abstract Background To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). Methods A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. Results CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p

Sorghum (Sorghum bicolor (L.) Moench) is a world cereal crop used in China for producing Baijiu, a distilled spirit. We report a telomere-to-telomere genome assembly of the Baijiu cultivar Hongyingzi, HYZ-T2T, using ultralong reads. The 10 chromosome pairs contained 33,462 genes, of which 93% were functionally annotated. The 20 telomeres and 10 centromeric regions on the HYZ-T2T chromosomes were predicted and two consecutive large inversions on chromosome 2 were characterized. A 65-gene reconstruction of the metabolic pathway of tannins, the flavor substances in Baijiu, was performed and may advance the breeding of sorghum cultivars for Baijiu production.

Abstract Background Recent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB. Results The results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ. Conclusions Our results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.

Abstract Based on dynamic monitoring data on China’s population, by using complex networks, spatial analysis and mathematical measurement, this study reveals the spatial characteristics and influencing factors of the network of flows of highly educated talents in the Yangtze River Delta region from the national and local perspectives. In the two perspectives, the network has strong isomorphism and certain differences. The in-flow of highly educated talents from cities with high administrative levels and more developed economies to Shanghai constitutes the core of the entire network. From a national perspective, highly educated talents tend to converge to the Yangtze River Delta region. From a local perspective, it was found that these talents cluster towards a limited number of cities in the region. From both perspectives, the flow network has developed into a “core-periphery” progressive hierarchical structure, with Shanghai becoming the sole core city. There is little difference in the influencing factors of talent mobility from both macro and meso perspectives. Highly educated talents would frequently flow between cities with strong economic development levels, and cities with high education level, scientific and technological level, complete infrastructure, and good aesthetics. However, geographical distance still plays a hindering role in the flow of highly educated talents, and factors such as cultural identity, institutional, and social modality differences among regions also have a certain effect on the flow of these talents.

Abstract Rheumatoid arthritis (RA) is a persistent autoimmune condition characterized by synovitis and joint damage. Recent findings suggest a potential link to abnormal lactate metabolism. This study aims to identify lactate metabolism-related genes (LMRGs) in RA and investigate their correlation with the molecular mechanisms of RA immunity. Data on the gene expression profiles of RA synovial tissue samples were acquired from the gene expression omnibus (GEO) database. The RA database was acquired by obtaining the common LMRDEGs, and selecting the gene collection through an SVM model. Conducting the functional enrichment analysis, followed by immuno-infiltration analysis and protein–protein interaction networks. The results revealed that as possible markers associated with lactate metabolism in RA, KCNN4 and SLC25A4 may be involved in regulating macrophage function in the immune response to RA, whereas GATA2 is involved in the immune mechanism of DC cells. In conclusion, this study utilized bioinformatics analysis and machine learning to identify biomarkers associated with lactate metabolism in RA and examined their relationship with immune cell infiltration. These findings offer novel perspectives on potential diagnostic and therapeutic targets for RA.

Abstract As for Atrazine (C8H14ClN5) degradation in soil, iron (Fe)-manganese (Mn) bimetallic biochar composites were proved to be more efficient for persulfate (PS) activation than monometallic ones. The atrazine removal rates of Fe/Mn loaded biochar + PS systems were 2.17–2.89 times higher than Fe/Mn loaded biochar alone. Compared with monometallic biochar, the higher atrazine removal rates by bimetallic biochar (77.2–96.7%) were mainly attributed to the synergy degradation and adsorption due to the larger amounts of metal oxides on the biochar surface. Atrazine degradation in Fe-rich biochar systems was mainly attributed to free radicals (i.e., $${\text{SO}}_{4}^{ \cdot - }$$ SO 4 · - and ·OH) through oxidative routes, whereas surface-bound radicals, 1O2, and free radicals were responsible for the degradation of atrazine in Mn-rich biochar systems. Furthermore, with a higher ratio of Fe(II) and Mn(III) formed in Fe-rich bimetallic biochar, the valence state exchange between Fe and Mn contributed significantly to the more effective activation of PS and the generation of more free radicals. The pathways of atrazine degradation in the Fe-rich bimetallic biochar systems involved alkyl hydroxylation, alkyl oxidation, dealkylation, and dechlorohydroxylation. The results indicated that bimetallic biochar composites with more Fe and less Mn are more effective for the PS-based degradation of atrazine, which guides the ration design of easily available carbon materials targeted for the efficient remediation of various organic-polluted soil. Graphical Abstract

Abstract Background Healthy lifestyle behaviors (LBs) have been widely recommended for the prevention and management of cardiovascular disease (CVD). Despite a large number of studies exploring the association between combined LBs and CVD, a notable gap exists in integration of relevant literatures. We conducted a systematic review and meta-analysis of prospective cohort studies to analyze the correlation between combined LBs and the occurrence of CVD, as well as to estimate the risk of various health complications in individuals already diagnosed with CVD. Methods Articles published up to February 10, 2023 were sourced through PubMed, EMBASE and Web of Science. Eligible prospective cohort studies that reported the relations of combined LBs with pre-determined outcomes were included. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using either a fixed or random-effects model. Subgroup analysis, meta-regression, publication bias, and sensitivity analysis were as well performed. Results In the general population, individuals with the healthiest combination of LBs exhibited a significant risk reduction of 58% for CVD and 55% for CVD mortality. For individuals diagnosed with CVD, adherence to the healthiest combination of LBs corresponded to a significant risk reduction of 62% for CVD recurrence and 67% for all-cause mortality, when compared to those with the least-healthy combination of LBs. In the analysis of dose-response relationship, for each increment of 1 healthy LB, there was a corresponding decrease in risk of 17% for CVD and 19% for CVD mortality within the general population. Similarly, among individuals diagnosed with CVD, each additional healthy LB was associated with a risk reduction of 27% for CVD recurrence and 27% for all-cause mortality. Conclusions Adopting healthy LBs is associated with substantial risk reduction in CVD, CVD mortality, and adverse outcomes among individuals diagnosed with CVD. Rather than focusing solely on individual healthy LB, it is advisable to advocate for the adoption of multiple LBs for the prevention and management of CVD. Trial registration PROSPERO: CRD42023431731.

Abstract Background Cell division cycle associated 5 (CDCA5) plays ontogenetic role in various human cancers. However, its specific function and regulatory mechanism in ccRCC remain uncertain. Methods Immunohistochemistry and western blots were performed to investigate the expression of CDCA5 in ccRCC tissues. Genetic knockdown and upregulation of CDCA5 were performed to investigate its functional roles in ccRCC proliferation, migration, apoptosis and sunitinib resistance. Furthermore, Co-IP assay and LC–MS/MS were performed to investigate the underlying mechanisms. Results We found that CDCA5 expression is frequently upregulated in ccRCC tumors and is associated with poor prognosis of ccRCC patients. Functionally, CDCA5 promotes proliferation, migration, and sunitinib resistance, while inhibiting apoptosis in ccRCC cells. In vivo mouse xenograft model confirms that silencing of CDCA5 drastically inhibits the growth of ccRCC. Mechanistically, we discovered that CDCA5 interacts with Eukaryotic Translation Elongation Factor 1 Alpha 1 (EEF1A1) to regulate mTOR signaling pathway, thereby promoting ccRCC progression. Conclusions Taken together, our results demonstrate the significant role of CDCA5 in ccRCC progression. The findings may provide insights for the development of new treatment strategies targeting CDCA5 for ccRCC patients.

Abstract Clouds, crucial for understanding climate, begin with droplet formation from aerosols, but observations of this fleeting activation step are lacking in the atmosphere. Here we use a time-gated time-correlated single-photon counting lidar to observe cloud base structures at decimeter scales. Results show that the air–cloud interface is not a perfect boundary but rather a transition zone where the transformation of aerosol particles into cloud droplets occurs. The observed distributions of first-arriving photons within the transition zone reflect vertical development of a cloud, including droplet activation and condensational growth. Further, the highly resolved vertical profile of backscattered photons above the cloud base enables remote estimation of droplet concentration, an elusive but critical property to understanding aerosol–cloud interactions. Our results show the feasibility of remotely monitoring cloud properties at submeter scales, thus providing much-needed insights into the impacts of atmospheric pollution on clouds and aerosol-cloud interactions that influence climate.

Abstract Background Suicide stands as both a primary symptom and the direst outcome of major depressive disorder (MDD). The scarcity of effective treatment strategies makes managing MDD patients with suicide especially challenging. Hence, it is crucial to investigate disease characteristics and efficacious therapeutic strategies for these patients, drawing insights from disease databases and real-world data. Methods In this retrospective study, MDD patients hospitalized between January 2013 and December 2020 were investigated using Electronic Health Records (EHR) data from Beijing Anding Hospital. The study enrolled 4138 MDD patients with suicidal ideation or behavior (MDS) and 3848 without (MDNS). Demographic data, clinical attributes, treatment approaches, disease burden, and re-hospitalization within one year of discharge were extracted and compared. Results Patients in the MDS group were predominantly younger and female, exhibiting a higher prevalence of alcohol consumption, experiencing frequent life stress events, and having an earlier onset age. Re-hospitalizations within six months post-discharge in the MDS group were significantly higher than in the MDNS group (11.36% vs. 8.91%, p

Abstract Object This study aimed to investigate the changes in the translucency and color of four different multi-layered zirconia materials when the sintering temperature were inaccurate. Materials and methods Two hundred zirconia samples (11 × 11 × 1.0 mm) of four multi-layered zirconia, Upcera TT-GT (UG), Upcera TT-ML (UM), Cercon xt ML (CX), and Lava Esthetic (LE), were divided into five subgroups according to the sintering temperature: L1 (5% lower temperature), L2 (2.5% lower temperature), R (recommended sintering temperature), H2 (2.5% higher temperature), H1 (5% higher temperature). After sintering, color coordinates were measured. Then the translucency parameter (TP) values, and the color differences (between the inaccurate sintering temperature and the recommended temperature) of each zirconia specimen were calculated. Statistical analysis was performed by using three-way ANOVA tests, the one-way ANOVA, and Tukey’s post hoc test. Results Three-way ANOVA results showed that material type, sintering temperature, specimen section, and their interactions significantly influenced the TP values (except for the interactions of specimen section and sintering temperature) (P .05). Compared with recommended sintering temperature, higher sintering temperature caused higher TP values for CX, but lower for LE. Three-way ANOVA results showed that material type, sintering temperature, and their interactions significantly influenced the ∆E 00 values (P

Abstract There has been a long-standing debate as to how many hydrogen bonds a peptide backbone amide can form in aqueous solution. Hydrogen-bonding structural dynamics of N-ethylpropionamide (a β-peptide model) in water was examined using infrared (IR) spectroscopy. Two amide-I sub bands arise mainly from amide C=O group that forms strong H-bonds with solvent water molecules (SHB state), and minorly from that involving one weak H-bond with water (WHB state). This picture is supported by molecular dynamics simulations and ab-initio calculations. Further, thermodynamics and kinetics of the SHB and WHB species were examined mainly by chemical-exchange two-dimensional IR spectroscopy, yielding an activation energy for the SHB-to-WHB exchange of 13.25 ± 0.52 kJ mol‒1, which occurs in half picosecond at room temperature. Our results provided experimental evidence of an unstable water molecule near peptide backbone, allowing us to gain more insights into the dynamics of the protein backbone hydration.

Abstract The hot corrosion experiments of René N5 alloy coated with three different NiCrAlY metal bonding layers are carried out, that the layers are prepared by different methods (APS, HVAF and MIP). Compared with bare René N5 alloy samples, the hot corrosion resistance of coated samples is improved. It can be attributed to the small internal stress of the surface oxide layer on the coating sample, which is difficult to spall, reducing the degree of hot corrosion reaction. The hot corrosion resistance of NiCrAlY layers is MIP > HVAF > APS, which is positively positively related to the density of layers, because the influence of element diffusion in the process of hot corrosion is effectively slowed down.

Abstract Treatment for inflammatory bowel disease (IBD) is challenging since current anti-inflammatory and immunosuppressive therapies do not address the underlying causes of the illness, which include increased levels of reactive oxygen species (ROS) and dysbiosis of the gut commensal microbiota. Additionally, these treatments often have systemic off-target effects and adverse side effects. In this study, we have developed a prebiotic yeast β-glucan nanocomplex coated with bio-adhesive polydopamine (YBNs@PDA) to effectively prolong their retention time in the gastrointestinal (GI) tract. The oral administration of YBNs@PDA restored the epithelium barriers, reduced ROS levels, and minimized systemic drug exposure while improved therapeutic efficacy in an acute colitis mouse model. Furthermore, 16S ribosomal RNA genes sequencing demonstrated a higher richness and diversity in gut microflora composition following the treatments. In particular, YBNs@PDA markedly augmented the abundance of Lachnospiraceae NK4A136 and Bifidobacterium, both of which are probiotics with crucial roles in relieving colitis via retaining gut homeostasis. Cumulatively, these results demonstrate that the potential of YBNs@PDA as a novel drug-free, ROS-scavenging and gut microbiota regulation nanoplatform for the treatment of GI disorders.

Abstract Background This study aimed to elucidate the methodology and assess the efficacy of the aortic arch inclusion technique using an artificial blood vessel in managing acute type A aortic dissection (ATAAD). Methods We conducted a retrospective review of 18 patients (11 males and 7 females, average age: 56.2 ± 8.6 years) diagnosed with ATAAD who underwent total aortic arch replacement (TAAR) using an artificial vascular “inclusion” between June 2020 and October 2022. During the operation, deep hypothermic circulatory arrest (DHCA) and selective antegrade cerebral perfusion (ACP) of the right axillary artery were employed for brain protection. The ‘inclusion’ total aortic arch replacement and stented elephant trunk (SET) surgery were performed. Results Four patients underwent the Bentall procedure during the study, with one additional patient requiring coronary artery bypass grafting (CABG) due to significant involvement of the right coronary orifice. Three patients died during postoperative hospitalization. Other notable complications included two cases of postoperative renal failure necessitating continuous renal replacement therapy (CRRT), one case of postoperative double lower limb paraplegia, and one case of cerebral infarction resulting in unilateral impairment of the left upper limb. Eleven patients underwent computed tomography angiography (CTA) examinations of the aorta three months to one-year post-operation. The CTA results revealed thrombosis in the false lumen surrounding the aortic arch stent in seven patients and complete thrombosis of the false lumen around the descending aortic stent in eight patients. One patient had partial thrombosis of the false lumen around the descending aortic stent, and another patient’s false lumen in the thoracic and abdominal aorta completely resolved after one year of follow-up. Conclusions Incorporating vascular graft in aortic arch replacement simplifies the procedure and yields promising short-term outcomes. It achieves the aim of total arch replacement using a four-branch prosthetic graft. However, extensive sampling and thorough, prolonged follow-up observations are essential to fully evaluate the long-term results.

Abstract Background Tartary buckwheat (Fagopyrum tataricum) belongs to Polygonaceae family and has attracted increasing attention owing to its high nutritional value. UDP-glycosyltransferases (UGTs) glycosylate a variety of plant secondary metabolites to control many metabolic processes during plant growth and development. However, there have been no systematic reports of UGT superfamily in F. tataricum. Results We identified 173 FtUGTs in F. tataricum based on their conserved UDPGT domain. Phylogenetic analysis of FtUGTs with 73 Arabidopsis UGTs clustered them into 21 families. FtUGTs from the same family usually had similar gene structure and motif compositions. Most of FtUGTs did not contain introns or had only one intron. Tandem repeats contributed more to FtUGTs amplification than segmental duplications. Expression analysis indicates that FtUGTs are widely expressed in various tissues and likely play important roles in plant growth and development. The gene expression analysis response to different abiotic stresses showed that some FtUGTs were involved in response to drought and cadmium stress. Our study provides useful information on the UGTs in F. tataricum, and will facilitate their further study to better understand their function. Conclusions Our results provide a theoretical basis for further exploration of the functional characteristics of FtUGTs and for understanding the growth, development, and metabolic model in F. tataricum.

Abstract Background Accumulating evidence indicates that aberrant non-SMC condensin II complex subunit D3 (NCAPD3) is associated with carcinogenesis of various cancers. Nevertheless, the biological role of NCAPD3 in the pathogenesis of non-small cell lung cancer (NSCLC) remains unclear. Methods Immunohistochemistry and Western blot were performed to assess NCAPD3 expression in NSCLC tissues and cell lines. The ability of cell proliferation, invasion, and migration was evaluated by CCK-8 assays, EdU assays, Transwell assays, and scratch wound healing assays. Flow cytometry was performed to verify the cell cycle and apoptosis. RNA-sequence and rescue experiment were performed to reveal the underlying mechanisms. Results The results showed that the expression of NCAPD3 was significantly elevated in NSCLC tissues. High NCAPD3 expression in NSCLC patients was substantially associated with a worse prognosis. Functionally, knockdown of NCAPD3 resulted in cell apoptosis and cell cycle arrest in NSCLC cells as well as a significant inhibition of proliferation, invasion, and migration. Furthermore, RNA-sequencing analysis suggested that NCAPD3 contributes to NSCLC carcinogenesis by regulating PI3K/Akt/FOXO4 pathway. Insulin-like growth factors-1 (IGF-1), an activator of PI3K/Akt signaling pathway, could reverse NCAPD3 silence-mediated proliferation inhibition and apoptosis in NSCLC cells. Conclusion NCAPD3 suppresses apoptosis and promotes cell proliferation via the PI3K/Akt/FOXO4 signaling pathway, suggesting a potential use for NCAPD3 inhibitors as NSCLC therapeutics.

Abstract The pathogenesis of Parkinson’s disease (PD) is strongly associated with neuroinflammation, and type I interferons (IFN-I) play a crucial role in regulating immune and inflammatory responses. However, the specific features of IFN in different cell types and the underlying mechanisms of PD have yet to be fully described. In this study, we analyzed the GSE157783 dataset, which includes 39,024 single-cell RNA sequencing results for five PD patients and six healthy controls from the Gene Expression Omnibus database. After cell type annotation, we intersected differentially expressed genes in each cell subcluster with genes collected in The Interferome database to generate an IFN-I-stimulated gene set (ISGs). Based on this gene set, we used the R package AUCell to score each cell, representing the IFN-I activity. Additionally, we performed monocle trajectory analysis, and single-cell regulatory network inference and clustering (SCENIC) to uncover the underlying mechanisms. In silico gene perturbation and subsequent experiments confirm NFATc2 regulation of type I interferon response and neuroinflammation. Our analysis revealed that microglia, endothelial cells, and pericytes exhibited the highest activity of IFN-I. Furthermore, single-cell trajectory detection demonstrated that microglia in the midbrain of PD patients were in a pro-inflammatory activation state, which was validated in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model as well. We identified transcription factors NFATc2, which was significantly up-regulated and involved in the expression of ISGs and activation of microglia in PD. In the 1-Methyl-4-phenylpyridinium (MPP+)-induced BV2 cell model, the suppression of NFATc2 resulted in a reduction in IFN-β levels, impeding the phosphorylation of STAT1, and attenuating the activation of the NF-κB pathway. Furthermore, the downregulation of NFATc2 mitigated the detrimental effects on SH-SY5Y cells co-cultured in conditioned medium. Our study highlights the critical role of microglia in type I interferon responses in PD. Additionally, we identified transcription factors NFATc2 as key regulators of aberrant type I interferon responses and microglial pro-inflammatory activation in PD. These findings provide new insights into the pathogenesis of PD and may have implications for the development of novel therapeutic strategies.

Abstract Super enhancers (SEs) consist of clusters of enhancers, harboring an unusually high density of transcription factors, mediator coactivators and epigenetic modifications. SEs play a crucial role in the maintenance of cancer cell identity and promoting oncogenic transcription. Super enhancer lncRNAs (SE-lncRNAs) refer to either transcript from SEs locus or interact with SEs, whose transcriptional activity is highly dependent on SEs. Moreover, these SE-lncRNAs can interact with their associated enhancer regions in cis and modulate the expression of oncogenes or key signal pathways in cancers. Inhibition of SEs would be a promising therapy for cancer. In this review, we summarize the research of SE-lncRNAs in different kinds of cancers so far and decode the mechanism of SE-lncRNAs in carcinogenesis to provide novel ideas for the cancer therapy.

Abstract Aiming at the problems of slow convergence speed and low precision probability of multi-objective optimization of energy storage materials, a multi-objective optimization model of energy storage materials based on NSGA-II algorithm was proposed. The association rule set of storage materials in the joint supply chain operation performance management system is extracted, and the rough vector feature distribution set multi-objective optimization method is used to decompose and optimize the characteristics of storage materials in the joint supply chain operation performance management system. Using NSGA-II optimization analysis method, this paper summarizes the power storage materials under the joint supply chain operation performance management system, and summarizes three kinds of inventory control: periodic inventory, inventory coding, and computerized inventory. Combined with the positive regression learning method of organizational operational performance, the multi-objective optimization decision of electric storage materials under the joint supply chain operational performance management system is realized. The simulation results show that under the joint supply chain operation performance management system, the proposed method reaches the optimal convergence after 65 iterations, the convergence speed is fast, and the accuracy probability reaches 1.000 after 80 iterations, which solves the problems of slow convergence speed and low accuracy probability, and has a good scheduling ability of energy storage materials.

Abstract Background Clinical scenarios frequently present challenges when patients exhibit asymmetrical mandibular atrophy. The dilemma arises: should we adhere to the conventional All-on-4 technique, or should we contemplate placing vertically oriented implants on the side with sufficient bone mass? This study aims to employ three-dimensional finite element analysis to simulate and explore the biomechanical advantages of each approach. Methods A finite element model, derived from computed tomography (CT) data, was utilized to simulate the nonhomogeneous features of the mandible. Three configurations—All-on-4, All-on-5-v and All-on-5-o were studied. Vertical and oblique forces of 200 N were applied unilaterally, and vertical force of 100 N was applied anteriorly to simulate different masticatory mechanisms. The maximum von Mises stresses on the implant and framework were recorded, as well as the maximum equivalent strain in the peri-implant bone. Results The maximum stress values for all designs were located at the neck of the distal implant, and the maximum strains in the bone tissue were located around the distal implant. The All-on-5-o and All-on-5-v models exhibited reduced stresses and strains compared to All-on-4, highlighting the potential benefits of the additional implant. There were no considerable differences in stresses and strains between the All-on-5-o and All-on-5-v groups. Conclusions With the presence of adequate bone volume on one side and severe atrophy of the contralateral bone, while the “All-on-4 concept” is a viable approach, vertical implant placement optimizes the transfer of forces between components and tissues.

Abstract Aims Acute myocardial infarction (MI) is a significant contributor to death in individuals diagnosed with coronary heart disease on a worldwide level. The specific mechanism by which circRbms1 contributes to the damage caused by myocardial ischaemia–reperfusion (I/R) is not well understood. The primary aim of this study was to examine the role of circRbms1 and its associated mechanisms in the setting of I/R injury. Methods and results An in vivo MI mice model and an in vitro MI cell model was established. The expression levels were detected using quantitative real‐time PCR (qRT‐PCR) and western blot. Cellular proliferation, apoptosis, pyroptosis, and autophagy were detected by immunostaining, immunohistochemistry, western blot, and transmission electron microscopy (TEM). Dual‐luciferase reporter assay, RNA pull‐down assay, and RIP assay were performed to validate the molecular interactions. CircRbms1 was up‐regulated in A/R‐induced HCMs and acted as a sponge for miR‐142‐3p, thereby targeting MST1. CircRbms1 could improve stability of MST1 by recruiting IGF2BP2 (all P

Brain-computer interfaces (BCIs) represent a groundbreaking approach to enabling direct communication for individuals with severe motor impairments, circumventing traditional neural and muscular pathways. Among the diverse array of BCI technologies, electroencephalogram (EEG)-based systems are particularly favored due to their non-invasive nature, user-friendly operation, and cost-effectiveness. Recent advancements have facilitated the development of adaptive bidirectional closed-loop BCIs, which dynamically adjust to users’ brain activity, thereby enhancing responsiveness and efficacy in neurorehabilitation. These systems support real-time modulation and continuous feedback, fostering personalized therapeutic interventions that align with users’ neural and behavioral responses. By incorporating machine learning algorithms, these BCIs optimize user interaction and promote recovery outcomes through mechanisms of activity-dependent neuroplasticity. This paper reviews the current landscape of EEG-based adaptive bidirectional closed-loop BCIs, examining their applications in the recovery of motor and sensory functions, as well as the challenges encountered in practical implementation. The findings underscore the potential of these technologies to significantly enhance patients’ quality of life and social interaction, while also identifying critical areas for future research aimed at improving system adaptability and performance. As advancements in artificial intelligence continue, the evolution of sophisticated BCI systems holds promise for transforming neurorehabilitation and expanding applications across various domains.

The estimation of postmortem interval (PMI) has long been a focal point in the field of forensic science. Following the death of an organism, microorganisms exhibit a clock-like proliferation pattern during the course of cadaver decomposition, forming the foundation for utilizing microbiology in PMI estimation. The establishment of PMI estimation models based on datasets from different seasons is of great practical significance. In this experiment, we conducted microbiota sequencing and analysis on gravesoil and mouse intestinal contents collected during both the winter and summer seasons and constructed a PMI estimation model using the Random Forest algorithm. The results showed that the MAE of the gut microbiota model in summer was 0.47 ± 0.26 d, R2 = 0.991, and the MAE of the gravesoil model in winter was 1.04 ± 0.22 d, R2 = 0.998. We propose that, in practical applications, it is advantageous to selectively build PMI estimation models based on seasonal variations. Additionally, through a combination of morphological observations, gravesoil microbiota sequencing results, and soil physicochemical data, we identified the time of cadaveric rupture for mouse cadavers, occurring at around days 24–27 in winter and days 6–9 in summer. This study not only confirms previous research findings but also introduces novel insights, contributing to the foundational knowledge necessary to advance the utilization of microbiota for PMI estimation.

IntroductionHigh-resolution whole-heart coronary magnetic resonance angiography (CMRA) often suffers from unreasonably long scan times, rendering imaging acceleration highly desirable. Traditional reconstruction methods used in CMRA rely on either hand-crafted priors or supervised learning models. Although the latter often yield superior reconstruction quality, they require a large amount of training data and memory resources, and may encounter generalization issues when dealing with out-of-distribution datasets.MethodsTo address these challenges, we introduce an unsupervised reconstruction method that combines deep image prior (DIP) with compressed sensing (CS) to accelerate 3D CMRA. This method incorporates a slice-by-slice DIP reconstruction and 3D total variation (TV) regularization, enabling high-quality reconstruction under a significant acceleration while enforcing continuity in the slice direction. We evaluated our method by comparing it to iterative SENSE, CS-TV, CS-wavelet, and other DIP-based variants, using both retrospectively and prospectively undersampled datasets.ResultsThe results demonstrate the superiority of our 3D DIP-CS approach, which improved the reconstruction accuracy relative to the other approaches across both datasets. Ablation studies further reveal the benefits of combining DIP with 3D TV regularization, which leads to significant improvements of image quality over pure DIP-based methods. Evaluation of vessel sharpness and image quality scores shows that DIP-CS improves the quality of reformatted coronary arteries.DiscussionThe proposed method enables scan-specific reconstruction of high-quality 3D CMRA from a five-minute acquisition, without relying on fully-sampled training data or placing a heavy burden on memory resources.

BackgroundChatGPT (OpenAI) has shown great potential in clinical diagnosis and could become an excellent auxiliary tool in clinical practice. This study investigates and evaluates ChatGPT in diagnostic capabilities by comparing the performance of GPT-3.5 and GPT-4.0 across model iterations. ObjectiveThis study aims to evaluate the precise diagnostic ability of GPT-3.5 and GPT-4.0 for colon cancer and its potential as an auxiliary diagnostic tool for surgeons and compare the diagnostic accuracy rates between GTP-3.5 and GPT-4.0. We precisely assess the accuracy of primary and secondary diagnoses and analyze the causes of misdiagnoses in GPT-3.5 and GPT-4.0 according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings. MethodsWe retrieved 316 case reports for intestinal cancer from the Chinese Medical Association Publishing House database, of which 286 cases were deemed valid after data cleansing. The cases were translated from Mandarin to English and then input into GPT-3.5 and GPT-4.0 using a simple, direct prompt to elicit primary and secondary diagnoses. We conducted a comparative study to evaluate the diagnostic accuracy of GPT-4.0 and GPT-3.5. Three senior surgeons from the General Surgery Department, specializing in Colorectal Surgery, assessed the diagnostic information at the Chinese PLA (People’s Liberation Army) General Hospital. The accuracy of primary and secondary diagnoses was scored based on predefined criteria. Additionally, we analyzed and compared the causes of misdiagnoses in both models according to 7 categories: patient histories, symptoms, physical signs, laboratory examinations, imaging examinations, pathological examinations, and intraoperative findings. ResultsOut of 286 cases, GPT-4.0 and GPT-3.5 both demonstrated high diagnostic accuracy for primary diagnoses, but the accuracy rates of GPT-4.0 were significantly higher than GPT-3.5 (mean 0.972, SD 0.137 vs mean 0.855, SD 0.335; t285=5.753; P

IntroductionsIdentifying patients with non-small cell lung cancer (NSCLC) who are optimal candidates for immunotherapy is a cornerstone in clinical decision-making. The tumor immune microenvironment (TIME) is intricately linked with both the prognosis of the malignancy and the efficacy of immunotherapeutic interventions. CD8+ T cells, and more specifically, tissue-resident memory CD8+ T cells [CD8+ tissue-resident memory T (TRM) cells] are postulated to be pivotal in orchestrating the immune system's assault on tumor cells. Nevertheless, the accurate quantification of immune cell infiltration—and by extension, the prediction of immunotherapeutic efficacy—remains a significant scientific frontier.MethodsIn this study, we introduce a cutting-edge non-invasive radiomic model, grounded in TIME markers (CD3+ T, CD8+ T, and CD8+ TRM cells), to infer the levels of immune cell infiltration in NSCLC patients receiving immune checkpoint inhibitors and ultimately predict their response to immunotherapy. Data from patients who had surgical resections (cohort 1) were employed to construct a radiomic model capable of predicting the TIME. This model was then applied to forecast the TIME for patients under immunotherapy (cohort 2). Conclusively, the study delved into the association between the predicted TIME from the radiomic model and the immunotherapeutic outcomes of the patients.ResultFor the immune cell infiltration radiomic prediction models in cohort 1, the AUC values achieved 0.765, 0.763, and 0.675 in the test set of CD3+ T, CD8+ T, and CD8+ TRM, respectively. While the AUC values for the TIME-immunotherapy predictive value were 0.651, 0.763, and 0.829 in the CD3-immunotherapy response model, CD8-immunotherapy response model, and CD8+ TRM-immunotherapy response model in cohort 2, respectively. The CD8+ TRM-immunotherapy model exhibited the highest predictive value and was significantly better than the CD3-immunotherapy model in predicting the immunotherapy response. The progression-free survival (PFS) analysis based on the predicted levels of CD3+ T, CD8+ T, and CD8+ TRM immune cell infiltration showed that the CD8+ T cell infiltration level was an independent factor (P=0.014, HR=0.218) with an AUC value of 0.938.DiscussionOur empirical evidence reveals that patients with substantial CD8+ T cell infiltration experience a markedly improved PFS compared with those with minimal infiltration, asserting the status of the CD8+ T cell as an independent prognosticator of PFS in the context of immunotherapy. Although CD8+ TRM cells demonstrated the greatest predictive accuracy for immunotherapy response, their predictive strength for PFS was marginally surpassed by that of CD8+ T cells. These insights advocate for the application of the proposed non-invasive radiomic model, which utilizes TIME analysis, as a reliable predictor for immunotherapy outcomes and PFS in NSCLC patients.

Gully erosion poses greater threat to ecological and food security globally. The gully development rate and the contributions of primary influencing factors have not been thoroughly understood, primarily due to the complicated environmental conditions characterized by climate, soil, topography, and human activities. Therefore, this study was conducted to explore the gully development and contributions of its driving factors from 2013 to 2021 based on historical Google Earth images and field investigation in a typical rolling hilly watershed of northeast China. The climatic factors reflected by precipitation, topographical factors related to gully, and anthropological factors reflected by tillage ridge orientation and linear anthropological factors (LAF) including roads and shelterbelts were obtained. The tillage effect index (TEI), LAF effect index (LEI) and the distance from gully to LAF (DL) were calculated to analyze the influence of anthropological factors on gully development. The results showed that the linear, areal and volumetric gully development rates (RL, RA and RV) showed great variabilities in different periods with the average of 5.69 m year−1, 137.37 m2 year−1 and 428.54 m3 year−1, respectively. The accumulated RL, RA and RV increased exponentially or linearly with accumulated precipitation amount (P), erosive rainfall duration (RD), erosive rainfall (ER), maximum 30-min rainfall intensity (I30) and rainfall erosivity (RE) increased (P

The Gross Domestic Product (GDP) per capita is one of the most widely used socioeconomic indicators, serving as an integral component for climate change impact analysis. However, a national scale assessment may induce considerable bias because it conceals any internal variations within a country. The lack of a long-term sub-national scale GDP data is a substantive hinderance. Leveraging the close relationship between nighttime lights and GDP, we address this gap by developing a novel methodological framework in two steps. First, under the modeling philosophy of spatial statistics, we developed a novel approach based on deep and machine learning techniques to establish a complex mapping between two inconsistent nighttime lights (NTL) datasets: the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP) and the National Polar-Orbiting Partnership’s Visible Infrared Imaging Radiometer Suite (VIIRS). The models achieve accuracies ranging from 0.945 to 0.980 (correlation coefficients). By taking the estimations ensemble of the two techniques, the time series of DMSP data was extended to 2021. Next, a novel modeling strategy based on multi-layer perceptron was developed to derive the non-linear relationship between NTL and GDP per capita at sub-national scale to alleviate scale effects at this granularity, while explicitly capturing regional heterogeneity effect. The trained models achieve average accuracies of 0.967, 0.959, and 0.959 on the training, validation, and test sets, respectively. We evaluate the developed dataset at the global, national, and sub-national scales from various perspective, and the results offer solid evidence on the reliability of the estimated economic data. By linking to historical global climate change data, we quantify global economic losses attributed to extreme heat to demonstrate how the estimated GDP data can be useful in the climate change impact analysis.