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Pulmonary arterial hypertension (PAH) is characterized by persistently elevated pulmonary artery pressure and vascular resistance. Sympathetic overactivity in hypertension participates in pulmonary vascular remodeling and heart failure. The present study aims to explore the efficacy of highly selective thoracic sympathectomy (HSTS) on lowering pulmonary artery pressure, reversing pulmonary vascular remodeling, and improving right ventricular function in rats. A total of 24 Sprague–Dawley rats were randomly assigned into the control group (n = 8) and experimental group (n = 16). Rats in the control group were intraperitoneally injected with 0.9% normal saline, and those in the experimental group were similarly administered with received monocrotaline (MCT) injections at 60 mg/kg. Two weeks later, rats in the experimental group were further subdivided randomly into the MCT-HSTS group (n = 8) and MCT-sham group (n = 8), and they were surgically treated with HSTS and sham operation, respectively. Two weeks later, significantly lowered mean pulmonary artery pressure (mPAP), pulmonary artery systolic pressure (sPAP), and the ratio of sPAP to femoral artery systolic pressure (sFAP) were detected in the MCT-HSTS group than those of the MCT-sham group. In addition, rats in the MCT-HSTS group presented a significantly lower ratio of vascular wall area to the total vascular area (WT%), right ventricular hypertrophy index, and degrees of right ventricular fibrosis and lung fibrosis in comparison to those of the MCT-sham group. HSTS significantly downregulated protein levels of inflammasomes in pulmonary artery smooth muscle cells (PASMCs). Collectively, HSTS effectively reduces pulmonary artery pressure, pulmonary arteriolar media hypertrophy, and right ventricular hypertrophy in MCT-induced PAH rats. It also exerts an anti-inflammatory effect on PASMCs in PAH rats by suppressing inflammasomes and the subsequent release of inflammatory cytokines.

Sarcopenia is often regarded as an early sign of weakness and is the core element of muscle weakness in elderly individuals. Sarcopenia is closely related to the reduction of exercise, and elderly individuals often suffer from decreased muscle mass and function due to a lack of exercise. At present, studies have confirmed that resistance and aerobic exercise are related to muscle mass, strength and fiber type and to the activation and proliferation of muscle stem cells (MuSCs). Increasing evidence shows that microRNAs (miRNAs) play an important role in exercise-related changes in the quantity, composition and function of skeletal muscle. At the cellular level, miRNAs have been shown to regulate the proliferation and differentiation of muscle cells. In addition, miRNAs are related to the composition and transformation of muscle fibers and involved in the transition of MuSCs from the resting state to the activated state. Therefore, exercise may delay sarcopenia in elderly individuals by regulating miRNAs in skeletal muscle. In future miRNA-focused treatment strategies, these studies will provide valuable information for the formulation of exercise methods and will provide useful and targeted exercise programs for elderly individuals with sarcopenia.

Abstract Background Microcystins are waterborne environmental toxins that induce oxidative stress and cause injuries in the heart. On the other hand, many physiological processes, including antioxidant defense, are under precise control by the mammalian circadian clock. Results In the present study, we evaluated the effect of microcystin-LR (MC-LR) on the rhythmic expression patterns of circadian and antioxidant genes in rat cardiomyocytes using the serum shock technique. We found that a non-toxic dose (10 μm) of MC-LR decreased the amplitudes of rhythmic patterns of clock genes, while it increased the expression levels of antioxidant genes. Conclusions Our results indicate an influence of MC-LR on the circadian clock system and clock-controlled antioxidant genes, which will shed some light on the explanation of heart toxicity induced by MC-LR from the viewpoint of chronobiology.

Background/Aims: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods: Whole-cell patch clamp recording was employed to record glycine-activated current (IGly) and Western blot was conducted to assess GlyRs subunits protein expression. Results: Application of TRPV4 agonist (GSK1016790A or 5,6-EET) increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047) and GlyR (strychnine), indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC) (BIM II or D-sphingosine) or calcium/calmodulin-dependent protein kinase II (CaMKII) (KN-62 or KN-93) antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv.) injected with GSK1016790A for 5 d. Conclusion: Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.

Individual Tree Detection-and-Counting (ITDC) is among the important tasks in town areas, and numerous methods are proposed in this direction. Despite their many advantages, still, the proposed methods are inadequate to provide robust results because they mostly rely on the direct field investigations. This paper presents a novel approach involving high-resolution imagery and the Canopy-Height-Model (CHM) data to solve the ITDC problem. The new approach is studied in six urban scenes: farmland, woodland, park, industrial land, road and residential areas. First, it identifies tree canopy regions using a deep learning network from high-resolution imagery. It then deploys the CHM-data to detect treetops of the canopy regions using a local maximum algorithm and individual tree canopies using the region growing. Finally, it calculates and describes the number of individual trees and tree canopies. The proposed approach is experimented with the data from Shanghai, China. Our results show that the individual tree detection method had an average overall accuracy of 0.953, with a precision of 0.987 for woodland scene. Meanwhile, the R2 value for canopy segmentation in different urban scenes is greater than 0.780 and 0.779 for canopy area and diameter size, respectively. These results confirm that the proposed method is robust enough for urban tree planning and management.

[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.

Total knee arthroplasty (TKA) is a well‐established treatment for end‐stage knee osteoarthritis. However, in patients with concomitant extra‐articular deformities, conventional TKA techniques may lead to unsatisfactory outcomes and higher complication rates. This review summarizes the application of navigated TKA for treating knee osteoarthritis with extra‐articular deformities. The principles and potential benefits of computer navigation systems, including improved component alignment, soft tissue balancing, and restoration of mechanical axis, are discussed. Research studies demonstrate that navigated TKA can effectively correct deformities, relieve pain, and improve postoperative joint function and quality of life compared with conventional methods. The advantages of navigated TKA in terms of surgical precision, lower complication rates, and superior functional recovery are highlighted. Despite challenges like the learning curve and costs, navigated TKA is an increasingly indispensable tool for achieving satisfactory outcomes in TKA for knee osteoarthritis patients with extra‐articular deformities.

AIM: To evaluate the refractive status through computer refractometer and OPD-Scan III auto refractometer in cataract patients after extended depth of focus(EDOF)intraocular lens implantation.METHODS: Retrospective observational study. A total of 61 cases(76 eyes)that received phacomulsification and implanted with TECNIS® Symfony ZXR00 intraocular lens in Shanghai Eye Diseases Prevention & Treatment Center from May 2022 to May 2023 were collected. Measurements from the computer refractometer, OPD-Scan III auto refractometer, and subjective refraction, were taken from all patients on the same day postoperatively.RESULTS: There were statistical significant difference in sphere(S)and spherical equivalent(SE)readings from the computer refractometer and subjective refraction(all P

Abstract As online learning and teaching are becoming an educational trend, online students’ engagement will directly impact the learning and teaching effects and outcomes. A scientific application of gamification in online learning, teaching, and online course design will improve online learners’ learning experience and help build a better virtual learning context for online learners worldwide. This study focuses on how gamification can engage online students from skills, emotional, participation, and performance perspectives. The gamification components investigated in this study are Points (also called Anar Seeds in the context of this study) and Badges, the most widely used components in gamification design in education, and online instructors have primarily used them to motivate students’ learning and acknowledge their achievements by timely rewarding specific learning behavior or performance. A mixed method has been applied to explore further the relationships between gamification components and online students’ engagement and how online students perceive the impacts of gamification on their online learning experience. The findings show a significant correlation between Points and online students’ skills, emotional, participation, and performance engagement, while it exists only between Badges and online students’ participation engagement. The findings also reveal mixed perceptions of online students towards gamification. Study limitations regarding lack of age criterion, limited measurement indicators, and oversimplification of survey responses have also been discussed. It is suggested that future research can be conducted from either the instructors’ or the gamification designers’ perspectives to determine any other factors that might contribute to the implementation of gamification in the online learning context.

The ablation mechanism of ablation-resistant silicone rubber was described and the research progress of ablation-resistant modification of silicone rubber by chemical modification such as block copolymerization, graft copolymerization and crosslinking or physical modification such as adding fillers and flame retardants at home and abroad was reviewed with 37 references. Finally, the future development direction of ablation-resistant silicone rubber was prospected.

Abstract Background The impact of extra-articular deformities (EADs) on lower limb alignment and collateral ligament integrity during total knee arthroplasty (TKA) poses significant challenges, increasing surgical complexity. Our study aims to evaluate the influence of EADs on mechanical axis alignment and the risk of collateral ligament injury during TKA using an AI-assisted surgical planning system, with the goal of minimizing ligament damage through precise and scientific planning. Methods A healthy volunteer underwent CT and MRI scans of the lower limbs. The scan images were imported into Mimics 20.0 software, and the reconstructed models were spatially aligned using 3-maticResearch 11.0 software. Using Unigraphics NX9.0 software, 50 three-dimensional models of femoral lateral joint deformities with varying positions and angles were created. Finally, TKA was simulated using the AI JOINT preoperative planning system. Results The larger the deformity angle and the closer it is to the knee joint, the more pronounced the deviation of the mechanical axis. During MA-aligned osteotomy, nine types of deformities can damage the collateral ligaments. After adjusting the varus/valgus of the prosthesis within a safe range of 3° and leaving a residual 3° varus/valgus in the lower limb alignment, only the 25° varus and 25° valgus deformities located at 90% of the femoral anatomical axis remain uncorrected. Conclusion For patients with osteoarthritis and concurrent EAD undergoing TKA, using reconstructed 3D models of the collateral ligaments for preoperative planning helps visually assess collateral ligament damage, providing a practical solution. Minimizing intra-articular osteotomies within a safe range and allowing some residual alignment deviation can reduce the risk of collateral ligament injury.

Objective A Bayesian net Meta-analysis was conducted to compare the efficacy of four traditional Chinese fitness Qigong techniques, namely, Baduanjin, Wuqinxi, Taijiquan, and Yijinjing, in treating cervical spondylosis, and their effects on pain relief and cervical spine function, in order to provide a reference for patients with cervical spondylosis in China in selecting the traditional fitness qigong treatment program. Methods Randomized controlled clinical trials on the treatment of cervical spondylosis with Ba Duan Jin, Taijiquan, Wu An Qigong and Yi Jin Jing were searched sequentially from PuBMed, Embase, Medline, CNKI, WanFang Data, VIP, and CBM, and the search time was set from the establishment of the database to August 7, 2023, and the results were reported by two researchers. Literature search and screening were performed by 2 researchers respectively, and then the included literature was subjected to data extraction and quality evaluation, using NoteExpress for literature screening, RevMan5. 4 software to draw literature risk of bias maps, the R software gemtc package, and JAGS software for Bayesian mesh meta-analysis, and stata17. 0 to draw the A "comparison-correction" funnel plot was drawn using stata17. 0 to evaluate whether there was publication bias in the included literature. Results A total of 40 papers were included, totaling 3236 patients with cervical spondylosis. Net Meta-analysis showed that in terms of total effectiveness, the top 3 fitness qigong programs were Baduanjin, Yijinjing, and Baduanjin + conventional treatment; In terms of VAS scores, the top 3 fitness qigong programs for pain reduction were Baduanjin, Yijinjing, and Taijiquan + conventional treatment; In terms of cervical vertebral dysfunction indices, the fitness qigong programs for cervical vertebrae improvement were Baduanjin + conventional treatment and Yijinjing. Conclusion Each of the four traditional Chinese fitness qigong exercises has its own advantages in the treatment of cervical spondylosis, and all of them have good clinical effects. However, this study showed that Ba Duan Jin is the best way to improve the efficacy and pain of patients with cervical spondylosis and has a good effect on cervical spondylosis patients of all ages. However, more high-quality randomized controlled trials are needed to confirm the results of this study, and doctors need to choose the best qigong according to the specific conditions of the patients in clinical treatment. (目的 采取贝叶斯网状Meta分析的方法比较八段锦、五禽戏、太极拳、易筋经4种中国传统健身气功治疗颈椎病的疗效以及对疼痛的缓解和颈椎功能的改善作用, 为国内颈椎病患者选取传统健身气功治疗方案提供参考依据。方法 依次检索数据PuBMed、Embase、Medline、中国知网(CNKI)、万方(WanFang Data)、维普数据库(VIP)、中国生物医学文献数据库(CBM)中有关八段锦、太极拳、五禽戏、易筋经治疗颈椎病的随机对照试验, 检索时限均为建库至2023年8月7日。由两名研究人员进行文献检索及筛选, 再将纳入的文献进行数据提取和质量评价, 使用NoteExpress软件进行文献筛选, RevMan5. 4软件绘制文献偏倚风险图, R软件gemtc包、JAGS软件进行贝叶斯网状meta分析, 使用Stata 17. 0绘制“比较-校正”漏斗图评价纳入文献是否存在发表偏倚。结果 共纳入40篇文献, 共计3236例颈椎病患者。网状Meta分析结果显示, 在总有效率方面, 疗效前3名的健身气功方案为八段锦、易筋经、八段锦+常规治疗; 在VAS评分方面, 减轻疼痛前3名的健身气功方案为八段锦、易筋经、太极拳＋常规治疗; 在颈椎功能障碍指数方面, 使颈椎功能得到改善的健身气功为八段锦+常规治疗、易筋经。结论 4种中国传统健身气功在治疗颈椎病时各有其优点, 皆具有良好的临床治疗效果。本研究显示八段锦是提高颈椎病患者疗效, 改善疼痛的最佳方式, 且对各年龄阶段的颈椎病患者都具有良好的改善作用, 但仍需要更多高质量的随机对照试验来证实其结果, 临床治疗时医生需根据患者的具体情况进行选择。)

Abstract Cardiomyocyte hypertrophy is a major outcome of pathological cardiac hypertrophy. The m6A demethylase ALKBH5 is reported to be associated with cardiovascular diseases, whereas the functional role of ALKBH5 in cardiomyocyte hypertrophy remains confused. We engineered Alkbh5 siRNA (siAlkbh5) and Alkbh5 overexpressing plasmid (Alkbh5 OE) to transfect cardiomyocytes. Subsequently, RNA immunoprecipitation (RIP)-qPCR, MeRIP-qPCR analysis and the dual-luciferase reporter assays were applied to elucidate the regulatory mechanism of ALKBH5 on cardiomyocyte hypertrophy. Our study identified ALKBH5 as a new contributor of cardiomyocyte hypertrophy. ALKBH5 showed upregulation in both phenylephrine (PE)-induced cardiomyocyte hypertrophic responses in vitro and transverse aortic constriction (TAC)/high fat diet (HFD)-induced pathological cardiac hypertrophy in vivo. Knockdown or overexpression of ALKBH5 regulated the occurrence of hypertrophic responses, including the increased cardiomyocyte surface areas and elevation of the hypertrophic marker levels, such as brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). Mechanically, we indicated that ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth. Our work highlights the functional role of ALKBH5 in regulating the onset of cardiomyocyte hypertrophy and provides a potential target for hypertrophic heart diseases prevention and treatment. ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth.

Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.

Practice is acknowledged as a crucial facilitator for musicians to achieve performance excellence. Despite the rich literature on incorporating musical imagery intentionally to improve one’s practice efficacy, limitations remain in the understanding of voluntary musical imagery (VMI) in the context of musical practice. Therefore, our aims in this review are threefold. First, we enriched the interpretation of VMI in the context of music practice through the lens of embodied cognition. Second, we integrated neuroscientific findings to elucidate how the deliberate use of musical imagery parallels physical practice in effectiveness. Third, we synthesize work on the application of VMI in enhancing musical learning from both theoretical and practical perspectives. By providing an integrated overview of voluntary musical imagery, we highlight gaps in the literature and encourage further research on (1) the impact of embodied experiences on VMI formation, (2) optimal imagery content and ratio combination to establish a personalized intervention protocol for more effective musical pedagogy, and (3) on physiological measures to access VMI effectiveness. Additionally, we highlight the crucial implications of VMI for researchers, performers, and music educators.

Grain boundaries are important microstructures in metallic materials, and dislocation nucleation on grain boundaries plays a crucial role in material deformation. Studies on P segregation on grain boundaries typically focus on segregation behavior at substitution or interstitial positions. Less attention is given to the interaction of a certain amount of P with dislocation nucleation and grain boundary structural units during deformation. Previous deformation mechanism studies often qualitatively determine mechanisms, struggling to quantitatively explain their roles. This paper offers an atomic mechanism for grain boundary dislocation nucleation, aiding in understanding of the effect of P segregation in BCC Fe on mechanical properties. In this paper, a large-scale atomic/molecular massively parallel simulation (LAMMPS) program was employed. It investigated the effect of P segregation in BCC Fe grain boundary on the tensile deformation behavior. Binary Fe-P embedded atom potential was used for the calculation of stress-strain curves and dislocation activation energy densities. The analysis of P segregation behavior on different grain boundary structures and the effect of temperature was conducted using visual analysis software (OVITO.3.10). To illustrate the elastic-plastic component of the strain during loading, a set of kinematic parameters based on continuum medium mechanics was employed. The atomic deformation tensor of the deformation gradient was calculated using the nearest-neighbor table approximation of the continuum medium field around each atom. Additionally, the mechanisms of dislocation nucleation and twinning were discussed for the symmetrically inclined grain boundaries in BCC Fe. For the (111) grain boundary system, dislocation nucleation extends and dominates the deformation behavior. For the (112) twin grain boundary system, tensile deformation is mainly controlled by twin grain boundary, resulting in BCC-FCC phase transitions. Tensile loads were applied to different grain boundaries at temperatures of 300 K and 600 K. The results indicate that, in the Fe-P system with P concentrations ranging from 0.05at.% to 0.2at.%, compared to enhancing the strength of (111) grain boundary systems, P segregation leads to a decrease in strength for (112) systems, but the effect is minor. The P segregation hinders dislocation nucleation on the (111) and (113) grain boundaries, while it promotes dislocation nucleation at (112) grain boundaries, and P segregation has no significant effect on dislocation nucleation at (114) grain boundaries. The degree of deformation of the E structural unit at the P segregated site on the (111) grain boundary is small, and the dislocations are more inclined to nucleate in the unsubstituted structural unit near the P atom.

AIM: To investigate the protective effect and mechanism of Danlou tablet on retinal ischemia-reperfusion injury(RIRI)in mice.METHODS: A total of 40 ApoE-/- mice were fed with high fat diet for 6 wk, and the RIRI model was established by anterior chamber infusion of pressurized saline. The mice were divided into control group(normal saline for 8 wk), RIRI model group(normal saline for 8 wk), and low-, medium-, and high-dose Danlou tablets groups [1, 2, and 4 g/(kg·d), respectively, for 8 wk]. The morphological changes of retina were observed by hematoxylin-eosin(HE)staining, retinal cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated Nick-End Labeling(TUNEL)staining. The Western-blot assay was used to detect the expression of retinal tissue sample Kelch-like ech-associated protein 1(Keap1), nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), and superoxide dismutase(Sod2)proteins.RESULTS: Compared with the control group, the mouse retina was atrophic with thinning thickness and increasing cell apoptosis, down-regulation of Sod2 protein expression, and up-regulation of Keap1 protein expression in the RIRI model group(all P0.05). The expression of Sod2, Nrf2 and HO-1 proteins up regulated, and the expression of Keap1 protein down regulated in the medium- and high-dose of Danlou tablets groups(all P

[Objective] This study was aimed to investigate the effects of organic manure replacing chemical fertilizer with equal nitrogen under different nitrogen application rates on the growth, yield and water-fertilizer use efficiency of spring maize in the dry zone of northern Shaanxi. [Methods] Multiple regression analysis and three-dimensional fitting models were used to establishing an optimal nitrogen management model for spring maize cultivation in northern Shaanxi. In this experiment, three nitrogen application levels (240, 180, 120 kg/hm2 for N1, N2, N3, respectively) and five organic manure replacing chemical fertilizer with equal nitrogen ratios (R0, R12.5, R25, R37.5, R50 for 100% chemical fertilizer nitrogen, 12.5% organic fertilizer nitrogen+87.5% chemical fertilizer nitrogen, 25% organic fertilizer nitrogen+75% chemical fertilizer nitrogen, 37.5% organic fertilizer nitrogen+62.5% chemical fertilizer nitrogen, 50% organic fertilizer nitrogen+50% chemical fertilizer nitrogen, respectively), a total of 15 treatments. During the main reproductive period of spring maize, spring maize growth and yield and yield components were measured, and water consumption (ET), water use efficiency (WUE), nitrogen fertilizer partial productivity (NPFP) and economic benefits were calculated. [Results] The Logistic function had a high fit for dry matter accumulation in spring maize, the R12.5 treatment delayed the start, the end and the appearance of the maximum value of the period of rapid dry matter accumulation, and the N2 treatment enhanced the maximum daily growth rate of dry matter accumulation. Nitrogen application and replacement ratio significantly affected dry matter accumulation, yield and components, ET, NPFP and economic efficiency of spring maize (p

Nocardiosis is an infectious disease caused by Nocardia spp., mainly affecting immunocompromised hosts. Nocardia infection is not common; especially Nocardia wallacei infection is even rarer. The patient, female, 61 years old, farmer, has been working in the field for a long time and has normal immune function. Her main clinical manifestation was persistent back pain. Chest-enhanced computed tomography showed pulmonary inflammation. Rare pathogen Nocardia wallacei was detected in alveolar lavage fluid using matrix-assisted laser destructive ionization time-of-flight mass spectrometry. She received treatment with linezolid and was discharged after her condition improved.

Abstract Background Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy. Methods We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U‐13C6]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level. Results The metabolomics analysis in myotubes revealed insulin‐like growth factor‐1 (IGF‐1)‐induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose‐5‐phosphate/ribulose‐5‐phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: −36.8%; P = 0.009). Like the hypertrophy stimulation with IGF‐1 in myotubes in vitro, the concentration of the dipeptide l‐carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose‐6‐phosphate, fructose‐6‐phosphate or glucose‐1‐phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF‐1‐stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U‐13C6]glucose is increasingly incorporated by ~13% (P = 0.001) into the non‐essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P

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 The dense mechanoreceptors in human fingertips enable texture discrimination. Recent advances in flexible electronics have created tactile sensors that effectively replicate slowly adapting (SA) and rapidly adapting (RA) mechanoreceptors. However, the influence of dermatoglyphic structures on tactile signal transmission, such as the effect of fingerprint ridge filtering on friction‐induced vibration frequencies, remains unexplored. A novel multi‐layer flexible sensor with an artificially synthesized skin surface capable of replicating arbitrary fingerprints is developed. This sensor simultaneously detects pressure (SA response) and vibration (RA response), enabling texture recognition. Fingerprint ridge patterns from notable historical figures – Rosa Parks, Richard Nixon, Martin Luther King Jr., and Ronald Reagan – are fabricated on the sensor surface. Vibration frequency responses to assorted fabric textures are measured and compared between fingerprint replicas. Results demonstrate that fingerprint topography substantially impacts skin‐surface vibrational transmission. Specifically, Parks' fingerprint structure conveyed higher frequencies more clearly than those of Nixon, King, or Reagan. This work suggests individual fingerprint ridge morphological variation influences tactile perception and can confer adaptive advantages for fine texture discrimination. The flexible bioinspired sensor provides new insights into human vibrotactile processing by modeling fingerprint‐filtered mechanical signals at the finger‐object interface.

Abstract Multi‐drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH‐sensitive photosensitizer‐drug conjugates (CyR‐SS‐L) are designed and synthesized. CyR‐SS‐L localized in the mitochondria then is cleaved into CyR‐SG and SG‐L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR‐SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG‐L part is used for chemotherapy. CyR‐SS‐L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR‐SS‐L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.

[Objective] Runoff changes under the combined influence of climate change and human activities. Exploring the temporal and spatial evolution of runoff and its causes has important guiding significance for the scientific operation of reservoirs and the sustainable use of water resources. [Methods] Based on the meteorological and hydrological data of the Wanzhou section of the Three Gorges Reservoir Area from 1960 to 2019, Mann-Kendall trend test, Pettitt mutation analysis and wavelet analysis were used to analyze the spatial and temporal evolution characteristics of runoff before and after the impoundment in the Three Gorges Reservoir Area. Finally, two Budyko hydrothermal coupling equilibrium equations were used to quantitatively calculate the influence rate of climate change and human activities on runoff change. [Results] (1) The annual runoff in the study area showed a significant downward trend (|z|>2.58), with the inflection point appearing in 2003 (the impoundment year of the Three Gorges Reservoir Area), after which the annual distribution was more uniform. (2) Compared to the period before impoundment, the contribution rates of climate change and human activities to the reduction of annual runoff in the study area after impoundment were 27.9% to 29.2% and 70.8% to 72.1%, respectively. (3) Human activities primarily influence the annual runoff of the basin by altering the type of land use and the construction of water conservation projects. [Conclusion] This study quantitatively describes the impact of human activities on runoff changes, and provides the oretical support for the next stage of water resources management in the Three Gorges Reservoir Area.

Abstract Background Patients infected with Acinetobacter baumannii (AB) bacteremia in hospital have high morbidity and mortality. We analyzed the clinical characteristics of pneumonia and nonpneumonia-related AB bloodstream infections (AB BSIs) and explored the possible independent risk factors for the incidence and prognosis of pneumonia-related AB BSIs. Methods A retrospective monocentric observational study was performed. All 117 episodes of hospital-acquired AB bacteremia sorted into groups of pneumonia-related AB BSIs (n = 45) and nonpneumonia-related AB BSIs (n = 72) were eligible. Univariate/multivariate logistic regression analysis was used to explore the independent risk factors. The primary outcome was the antibiotic susceptibility in vitro of pneumonia-related AB BSIs group. The secondary outcome was the independent risk factor for the pneumonia-related AB BSIs group. Results Among 117 patients with AB BSIs, the pneumonia-related group had a greater risk of multidrug resistant A. baumannii (MDRAB) infection (84.44%) and carbapenem-resistant A. baumannii (CRAB) infection (80%). Polymyxin, minocycline and amikacin had relatively high susceptibility rates (> 80%) in the nonpneumonia-related group. However, in the pneumonia-related group, only polymyxin had a drug susceptibility rate of over 80%. Univariate analysis showed that survival time (day), CRAB, MDRAB, length of hospital stay prior to culture, length of ICU stay prior to culture, immunocompromised status, antibiotics used prior to culture (n > = 3 types), endotracheal tube, fiberoptic bronchoscopy, PITT, SOFA and invasive interventions (n > = 3 types) were associated with pneumonia-related AB bacteremia. The multivariate logistic regression analysis revealed that recent surgery (within 1 mo) [P = 0.043; 0.306 (0.098–0.962)] and invasive interventions (n > = 3 types) [P = 0.021; 0.072 (0.008–0.671)] were independent risk factors related to pneumonia-related AB bacteremia. Multivariate logistic regression analysis revealed that length of ICU stay prior to culture [P = 0.009; 0.959 (0.930–0.990)] and recent surgery (within 1 mo) [P = 0.004; 0.260 (0.105–0.646)] were independent risk factors for mortality in patients with pneumonia-related AB bacteremia. The Kaplan‒Meier curve and the timing test showed that patients with pneumonia-related AB bacteremia had shorter survival time compared to those with nonpneumonia-related AB bacteremia. Conclusions Our study found that A. baumannii had a high rate of antibiotic resistance in vitro in the pneumonia-related bacteremia group, and was only sensitive to polymyxin. Recent surgery was a significantly independent predictor in patients with pneumonia-related AB bacteremia.

Abstract The root-associated microbiota plays an important role in the response to environmental stress. However, the underlying mechanisms controlling the interaction between salt-stressed plants and microbiota are poorly understood. Here, by focusing on a salt-tolerant plant wild soybean (Glycine soja), we demonstrate that highly conserved microbes dominated by Pseudomonas are enriched in the root and rhizosphere microbiota of salt-stressed plant. Two corresponding Pseudomonas isolates are confirmed to enhance the salt tolerance of wild soybean. Shotgun metagenomic and metatranscriptomic sequencing reveal that motility-associated genes, mainly chemotaxis and flagellar assembly, are significantly enriched and expressed in salt-treated samples. We further find that roots of salt stressed plants secreted purines, especially xanthine, which induce motility of the Pseudomonas isolates. Moreover, exogenous application for xanthine to non-stressed plants results in Pseudomonas enrichment, reproducing the microbiota shift in salt-stressed root. Finally, Pseudomonas mutant analysis shows that the motility related gene cheW is required for chemotaxis toward xanthine and for enhancing plant salt tolerance. Our study proposes that wild soybean recruits beneficial Pseudomonas species by exudating key metabolites (i.e., purine) against salt stress.

Abstract In their natural habitats, microbes rarely exist in isolation; instead, they thrive in consortia, where various interactions occur. In this study, a defined synthetic co-culture of the cyanobacterium S. elongatus cscB, which supplies sucrose to the heterotrophic P. putida cscRABY, is investigated to identify potential interactions. Initial experiments reveal a remarkable growth-promoting effect of the heterotrophic partner on the cyanobacterium, resulting in an up to 80% increase in the growth rate and enhanced photosynthetic capacity. Vice versa, the presence of the cyanobacterium has a neutral effect on P. putida cscRABY, highlighting the resilience of pseudomonads against stress and their potential as co-culture partners. Next, a suitable reference process reinforcing the growth-promoting effect is established in a parallel photobioreactor system, which sets the basis for the analysis of the co-culture at the transcriptome, proteome, and metabolome levels. In addition to several moderate changes, including alterations in the metabolism and stress response in both microbes, this comprehensive multi-OMICs approach strongly hints towards the exchange of further molecules beyond the unidirectional feeding with sucrose. Taken together, these findings provide valuable insights into the complex dynamics between both co-culture partners, indicating multi-level interactions, which can be employed for further streamlining of the co-cultivation system.

Snapshot spectral imaging technology enables the capture of complete spectral information of objects in an extremely short period of time, offering wide-ranging applications in fields requiring dynamic observations such as environmental monitoring, medical diagnostics, and industrial inspection. In the past decades, snapshot spectral imaging has made remarkable breakthroughs with the emergence of new computational theories and optical components. From the early days of using various spatial-spectral data mapping methods, they have evolved to later attempts to encode various dimensions of light, such as amplitude, phase, and wavelength, and then computationally reconstruct them. This review focuses on a systematic presentation of the system architecture and mathematical modeling of these snapshot spectral imaging techniques. In addition, the introduction of metasurfaces expands the modulation of spatial-spectral data and brings advantages such as system size reduction, which has become a research hotspot in recent years and is regarded as the key to the next-generation snapshot spectral imaging techniques. This paper provides a systematic overview of the applications of metasurfaces in snapshot spectral imaging and provides an outlook on future directions and research priorities.

Abstract Background miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined. Methods To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter. Bone marrow cells were isolated from miR-182 knockout (182KO) and 182 wild type (182WT) mice to construct BCR-ABL (P190) and Notch-induced murine B-ALL and T-ALL models, respectively. Primary ALL samples were performed to investigate synergistic effects of the hypomethylation agents (HMAs) and the BCL2 inhibitor venetoclax (Ven) in vitro. Results miR-182 (miR-182-5P) expression was substantially lower in ALL blasts than in normal controls (NCs) because of DNA hypermethylation at the miR-182 promoter in ALL blasts but not in normal controls (NCs). Knockout of miR-182 (182KO) markedly accelerated ALL development, facilitated the infiltration, and shortened the OS in a BCR-ABL (P190)-induced murine B-ALL model. Furthermore, the 182KO ALL cell population was enriched with more leukemia-initiating cells (CD43+B220+ cells, LICs) and presented higher leukemogenic activity than the 182WT ALL population. Furthermore, depletion of miR-182 reduced the OS in a Notch-induced murine T-ALL model, suggesting that miR-182 knockout accelerates ALL development. Mechanistically, overexpression of miR-182 inhibited proliferation and induced apoptosis by directly targeting PBX3 and BCL2, two well-known oncogenes, that are key targets of miR-182. Most importantly, DAC in combination with Ven had synergistic effects on ALL cells with miR-182 promoter hypermethylation, but not on ALL cells with miR-182 promoter hypomethylation. Conclusions Collectively, we identified miR-182 as a tumor suppressor gene in ALL cells and low expression of miR-182 because of hypermethylation facilitates the malignant phenotype of ALL cells. DAC + Ven cotreatment might has been applied in the clinical try for ALL patients with miR-182 promoter hypermethylation. Furthermore, the methylation frequency at the miR-182 promoter should be a potential biomarker for DAC + Ven treatment in ALL patients.

Abstract Poa pratensis L. (Poaceae) is a valuable grass across the north hemisphere, inhabiting diverse environments with wide altitudinal span, where ubiquitous various kinds of stresses. Phytohormones would be helpful to improve tolerance to abiotic and biotic stresses, but the responses of transcriptome regulation of P. pratensis to exogenous phytohormones application remain unclear. In this study, we explored the alteration of plant physiological responses by the application of phytohormones. Aiming to achieve this knowledge, we got full-length transcriptome data 42.76 Gb, of which 74.9% of transcripts were completed. Then used 27 samples representing four treatments conducted at two time points (1 h and 6 h after application) to generate RNA-seq data. 371 and 907 common DEGs were identified in response to four phytohormones application, respectively, these DEGs were involved in “plant hormone signal transduction”, “carbon metabolism” and “plant-pathogen interaction”. Finally, P. pratensis basic research can gain valuable information regarding the responses to exogenous application of phytohormones in physiological indicators and transcriptional regulations in order to facilitate the development of new cultivars.

The conventional operation mode of “power determined by heat” employed by thermal power plants， along with the randomness and volatility of new energy power generation， constrains the peak regulation capacity. The incorporation of thermal storage technology into grid peak regulation can optimize the allocation capacity of the energy system. The fundamental principles， appropriate materials， advantages， disadvantages， and future development trends of three different thermal storage technologies， namely， sensible heat storage （SHS）， latent heat storage （LHS） and chemical energy storage （CES）， are introduced. Furthermore， the strategies of different thermal storage technologies for power system peak regulation at home and abroad as well as the applications of actual peak regulation projects are discussed. Given the special working conditions faced by thermal storage technology in power grid peak regulation， four critical evaluation criteria， including safety， performance matching， reliability and economy that must be considered for thermal storage technology to participate in power grid peak regulation are proposed. The main business models， including energy management contracting （EMC）， two-part tariff （TPT）， and ancillary service market （ASM） for thermal storage to participate in power trading are explored. These models serve as valuable references for enabling the widespread commercial operation of thermal storage technology within the context of grid peak regulation.

Abstract Background Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. Methods Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. Results We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. Conclusions Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

The interfacial interaction between Kevlar nanofiber modified by epichlorohydrin (m-KNFs) and carboxylated nitrile butadiene rubber (XNBR), and m-KNFs and styrene-butadiene rubber (SBR), and the effect of m-KNFs on the property of the composite were studied by experiment and molecular simulation. The research results showed that m-KNFs had a significant enhancing effect on rubber systems; compared with the m-KNFs/SBR and m-KNFs/XNBR/SBR systems, there were the most hydrogen bonds in the m-KNFs/XNBR system; compared with XNBR, tensile strength of m-KNFs/XNBR nanocomposite increased by 182%, mainly due to the strong hydrogen bonding network structure formed between m-KNF and XNBR matrix, which had the strongest interfacial interaction and the best compatibility.