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Abstract Background Primordial follicle activation is vital for the reproduction of women with advanced age and premature ovarian insufficiency (POI). But there is a lack of effective and safe therapeutic options to activate their primordial follicles in vivo. Berberine (BBR) possesses multiple pharmacological properties, but its impact on primordial follicle activation remains unclear. Methods The role of BBR on primordial activation was investigated by neonatal mouse ovary culture and intraperitoneal injection, and by human ovarian fragment culture. Furthermore, the effect of BBR on the quantity of ovulated oocytes was investigated by the intragastric administration of aged mice. Results BBR in vitro culture and in vivo intraperitoneal injection significantly increased growing follicle number and phosphorylated protein kinase B (p-Akt) levels in neonatal mouse ovaries. BBR also significantly increased the relative fluorescence intensities of p-Akt in the oocytes of primordial follicles. BBR-increased the number of growing follicles and the levels of p-Akt were blocked by LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K). Furthermore, BBR intragastric administration significantly increased the quantity of ovulated oocytes in aged mice. Moreover, BBR significantly increased growing follicle proportion and p-Akt levels in cultured human ovarian fragments. Conclusion BBR promotes mouse and human primordial follicle activation through the PI3K/Akt pathway in oocytes, and improves the quantity of ovulated oocytes in aged mice. Our results suggest a potential use of oral medicine BBR to improve fertility in POI patients and aged women.

In recent years, the increase in people’s demand for energy has led to the development of secondary batteries. Because of its high theoretical capacity and low electrochemical potential, lithium metal has gradually become the preferred negative electrode material for high-energy-density secondary batteries and has great application prospects in the field of energy storage technology. However, the practical application of lithium metal anodes faces major challenges mainly because of the inevitable formation of lithium dendrites and dead lithium during the charge–discharge cycle. These problems considerably reduce the Coulomb efficiency and service life of lithium metal batteries and constitute a substantial obstacle to the development and wide application of lithium metal batteries. Lithium dendrites are tree-like structures formed by uneven lithium deposition during the charging of lithium metal. These dendrites can penetrate the diaphragm and reach the cathode, causing a short circuit that can lead to catastrophic battery failure. Dead lithium refers to lithium that is separated from the anode during the discharging of a lithium battery and no longer participates in subsequent electrochemical reactions. The accumulation of dead lithium reduces the inventory of active lithium, causing battery capacity and efficiency to decline over time. Addressing these challenges requires an in-depth understanding of the formation mechanisms of lithium dendrites and dead lithium and their influencing factors. This study focuses on analyzing these mechanisms and influencing factors from the perspective of the phase field, which is a powerful computational method to simulate microstructure evolution, providing insights into the complex dynamics of lithium deposition and the conditions and influencing factors for the formation of lithium dendrites and dead Lithium. The latest research progress on the inhibition of dead lithium by temperature, pressure, diaphragm, bubble, and high active electrolyte was reviewed. First, the influence of temperature and pressure on the formation of dead lithium and the effect of two coupling fields on dead lithium are discussed. Second, starting from the diaphragm and electrolyte, the results of researchers in recent years are reviewed. For example, selecting a diaphragm with the appropriate pore size can promote the uniform deposition of lithium, better prevent the penetration of dendrites, and promote the resurrection of dead lithium. The highly active electrolyte can enhance the smooth deposition of lithium and inhibit the formation of dead lithium. These factors can regulate the deposition form of lithium to a certain extent and slow down or avoid the formation of lithium dendrites and dead lithium. By optimizing these factors, researchers can better control the deposition morphology of lithium, alleviating or even avoiding the formation of lithium dendrites and dead lithium. The phase field method is used to determine how the formation of dead lithium affects the overall life of the battery. The phase field is also used to simulate the long-term behavior of lithium metal anodes to predict the battery life under various operating conditions. Finally, this paper discusses and summarizes the shortcomings of the existing phase field method in the study of the radical elimination of dead lithium and the prospects for future development.

Abstract Introduction Pyroptosis, inflammatory necrosis of cells, is a programmed cell death involved in the pathological process of diseases. Endoplasmic reticulum stress (ERS), as a protective stress response of cell, decreases the unfold protein concentration to inhibit the unfold protein agglutination. Whereas the relationship between endoplasmic reticulum stress and pyroptosis in pulmonary hypertension (PH) remain unknown. Previous evident indicated that circular RNA (circRNA) can participate in several biological process, including cell pyroptosis. However, the mechanism of circRNA regulate pyroptosis of pulmonary artery smooth muscle cells through endoplasmic reticulum stress still unclear. Here, we proved that circSSR1 was down-regulate expression during hypoxia in pulmonary artery smooth muscle cells, and over-expression of circSSR1 inhibit pyroptosis both in vitro and in vivo under hypoxic. Our experiments have indicated that circSSR1 could promote host gene SSR1 translation via m6A to activate ERS leading to pulmonary artery smooth muscle cell pyroptosis. In addition, our results showed that G3BP1 as upstream regulator mediate the expression of circSSR1 under hypoxia. These results highlight a new regulatory mechanism for pyroptosis and provide a potential therapy target for pulmonary hypertension. Methods RNA-FISH and qRT-PCR were showed the location of circSSR1 and expression change. RNA pull-down and RIP verify the circSSR1 combine with YTHDF1. Western blotting, PI staining and LDH release were used to explore the role of circSSR1 in PASMCs pyroptosis. Results CircSSR1 was markedly downregulated in hypoxic PASMCs. Knockdown CircSSR1 inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circSSR1 combine with YTHDF1 to promote SSR1 protein translation rely on m6A, activating pyroptosis via endoplasmic reticulum stress. Furthermore, G3BP1 induce circSSR1 degradation under hypoxic. Conclusion Our findings clarify the role of circSSR1 up-regulated parental protein SSR1 expression mediate endoplasmic reticulum stress leading to pyroptosis in PASMCs, ultimately promoting the development of pulmonary hypertension.

【Objective】In the context of increasing global and regional external shocks threatening food security, enhancing the resilience of food supply chains is of paramount importance. The study aims to explore whether agricultural digitalization can significantly enhance the resilience of food supply chains, and it delves into the underlying mechanisms to provide decision-making support for governments and agricultural stakeholders.【Method】Based on the panel data from 31 provinces in China between 2013 and 2022, the baseline regression method and panel threshold model were used to examine the impacts of agricultural digitalization on the resilience of food supply chains. Robustness checks were performed by substituting explained variables, excluding municipal samples, and using instrumental variables for endogeneity test. In addition, regional heterogeneity was analyzed to investigate differences among regions, and the threshold effect of agricultural subsidies was tested.【Result】Agricultural digitalization has significantly enhanced the resilience of the food supply chain, with transaction digitalization playing a pivotal role in this improvement. Specifically, the coefficient for the improvement of agricultural digitalization on food supply chain resilience is 0.108 (P < 0.01), which is further validated through robustness checks. Regional heterogeneity analysis reveals that agricultural digitalization has the most significant positive effect on food supply chain resilience in the western region, followed by. the central region, while the eastern region shows an insignificant. Moreover, agricultural fiscal subsidies exhibit a threshold effect, where the positive impact of digitalization on resilience increases substantially (P < 0.01) once subsidy levels exceed the specific threshold value (0.8996).【Conclusion】Agricultural digitalization is an important pathway for enhancing the resilience of the food supply chain, particularly through transaction digitalization, which accelerates information flow and increases market transparency. Given regional disparities, It is essential to leverage the threshold effect by adjusting agricultural fiscal subsidy policies and promoting the development of regional digital trading platforms, thereby enhancing the stability and flexibility of food supply chains and ensuring food security comprehensively.

Abstract Liver metastasis is the major cause of death in colorectal cancer (CRC) due to the lack of effective treatment. To explore novel drivers of CRC liver metastasis, the transcriptomes of primary paracancerous, colorectal tumors and metastases from human patients are profiled. It is found that SLIT‐ and NTRK‐like family member 4 (SLITRK4) is the top upregulated gene in liver metastases and is associated with worse overall survival of CRC patients. Multiple in vitro and in vivo models suggested SLITRK4 promoted CRC tumorigenesis, invasion, migration, and angiogenesis, and inhibition of it restrained CRC tumor growth and liver metastasis with a more profound effect on the tumor microenvironment (TME). Mechanistically, SLITRK4 overexpression significantly activated the PI3K/AKT/NFκB pathway, regulated extracellular matrix organization, and multiple cytokines expression. Furthermore, the results from coculture models and single‐cell RNA sequencing analyses suggested SLITRK4 promoted tumor‐associated macrophages (TAMs) infiltration and polarization. In addition, macrophage depletion significantly inhibited SLITRK4‐induced liver metastasis in CRC. Finally, pharmacological inhibition of SLITRK4 by using lipid‐polymer hybrid nanoparticles (NPs) for systemic siRNA delivery can effectively inhibit CRC liver metastasis. Taken together, these results pinpoint that SLITRK4 regulates CRC tumorigenesis and liver metastasis, and siRNA delivering NPs agents validate the therapeutic potential of targeting SLITRK4 in CRC.

Background Pulmonary hypertension is a rare, progressive disorder that can lead to right ventricular hypertrophy, right heart failure, and even sudden death. N6‐methyladenosine modification and the main methyltransferase that mediates it, methyltransferase‐like (METTL) 3, exert important effects on many biological and pathophysiological processes. However, the role of METTL3 in pyroptosis remains unclear. Methods and Results Here, we characterized the role of METTL3 and the underlying cellular and molecular mechanisms of pyroptosis, which is involved in pulmonary hypertension. METTL3 was downregulated in a pulmonary hypertension mouse model and in hypoxia‐exposed pulmonary artery smooth muscle cell. The small interfering RNA–induced silencing of METTL3 decreased the m6A methylation levels and promoted pulmonary artery smooth muscle cell pyroptosis, mimicking the effects of hypoxia. In contrast, overexpression of METTL3 suppressed hypoxia‐induced pulmonary artery smooth muscle cell pyroptosis. Mechanistically, we identified the phosphate and tension homology deleted on chromosome 10 (PTEN) gene as a target of METTL3‐mediated m6A modification, and methylated phosphate and tension homology deleted on chromosome 10 mRNA was subsequently recognized by the m6A “reader” protein insulin‐like growth factor 2 mRNA‐binding protein 2, which directly bound to the m6A site on phosphate and tension homology deleted on chromosome 10 mRNA and enhanced its stability. Conclusions These results identify a new signaling pathway, the METTL3/phosphate and tension homology deleted on chromosome 10/insulin‐like growth factor 2 mRNA‐binding protein 2 axis, that participates in the regulation of hypoxia‐induced pyroptosis.

Sugar beets account for 30% of global sugar production each year, and their byproducts are an important source of bioethanol and animal feed. Sugar beet is an important cash crop in Inner Mongolia, China. To achieve high yields and sugar content, it is essential to supply nitrogen fertilizer in accordance with the growth characteristics of sugar beet, thereby enhancing the efficiency of nitrogen fertilizer utilization. A two-year experiment was carried out in the experimental field of the Inner Mongolia Academy of Agricultural & Animal Husbandry Sciences. The impact of varying ratios of nitrogen-based fertilizer to topdressing on nitrate nitrogen and ammonium nitrogen levels in the 20–60 cm soil layer, as well as the activities of protease, urease, catalase, and sucrose in the 20–40 cm soil layer were investigated during the rapid leaf growth period and root and sugar growth period. Results indicated that different ratios of nitrogen-based fertilizer to topdressing significantly influenced the levels of nitrate nitrogen and ammonium nitrogen, and the activities of protease and urease in the 0–20 cm soil layer, with these effects diminishing as soil depth increased. The activities of catalase and sucrose were minimally impacted. Nitrogen was applied at 150 kg/ha during the growth period of sugar beet, according to the growth characteristics of sugar beet to maximize nitrogen utilization efficiency. Topdressing was completed with irrigation at the rapid growth stage. The nitrogen-based fertilizer to topdressing ratio of 6:4 resulted in optimal crop yield and sugar yield of sugar beet under shallow drip irrigation. Additionally, the activities of protease and urease in different soil treatments were significantly different, and the activities of protease and urease in the 0–40 cm soil layer were identified as useful soil physiological indicators for nitrogen utilization in sugar beet.

Abstract Background Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI), but the underlying pathogenesis remains largely unknown. Methods and results We generated eukaryotic translation initiation factor 5 (Eif5) conditional knockout mice aiming to investigate the function of eIF5 during oocyte growth and follicle development. Here, we demonstrated that Eif5 deletion in mouse primordial and growing oocytes both resulted in the apoptosis of oocytes within the early‐growing follicles. Further studies revealed that Eif5 deletion in oocytes downregulated the levels of mitochondrial fission‐related proteins (p‐DRP1, FIS1, MFF and MTFR) and upregulated the levels of the integrated stress response‐related proteins (AARS1, SHMT2 and SLC7A1) and genes (Atf4, Ddit3 and Fgf21). Consistent with this, Eif5 deletion in oocytes resulted in mitochondrial dysfunction characterized by elongated form, aggregated distribution beneath the oocyte membrane, decreased adenosine triphosphate content and mtDNA copy numbers, and excessive accumulation of reactive oxygen species (ROS) and mitochondrial superoxide. Meanwhile, Eif5 deletion in oocytes led to a significant increase in the levels of DNA damage response proteins (γH2AX, p‐CHK2 and p‐p53) and proapoptotic proteins (PUMA and BAX), as well as a significant decrease in the levels of anti‐apoptotic protein BCL‐xL. Conclusion These findings indicate that Eif5 deletion in mouse oocytes results in the apoptosis of oocytes within the early‐growing follicles via mitochondrial fission defects, excessive ROS accumulation and DNA damage. This study provides new insights into pathogenesis, genetic diagnosis and potential therapeutic targets for POI. Key points Eif5 deletion in oocytes leads to arrest in oocyte growth and follicle development. Eif5 deletion in oocytes impairs the translation of mitochondrial fission‐related proteins, followed by mitochondrial dysfunction. Depletion of Eif5 causes oocyte apoptosis via ROS accumulation and DNA damage response pathway.

Abstract Mesoporous silica nanoparticles (MSNs) are recognized as a prime example of nanotechnology applied in the biomedical field, due to their easily tunable structure and composition, diverse surface functionalization properties, and excellent biocompatibility. Over the past two decades, researchers have developed a wide variety of MSNs-based nanoplatforms through careful design and controlled preparation techniques, demonstrating their adaptability to various biomedical application scenarios. With the continuous breakthroughs of MSNs in the fields of biosensing, disease diagnosis and treatment, tissue engineering, etc., MSNs are gradually moving from basic research to clinical trials. In this review, we provide a detailed summary of MSNs in the biomedical field, beginning with a comprehensive overview of their development history. We then discuss the types of MSNs-based nanostructured architectures, as well as the classification of MSNs-based nanocomposites according to the elements existed in various inorganic functional components. Subsequently, we summarize the primary purposes of surface-functionalized modifications of MSNs. In the following, we discuss the biomedical applications of MSNs, and highlight the MSNs-based targeted therapeutic modalities currently developed. Given the importance of clinical translation, we also summarize the progress of MSNs in clinical trials. Finally, we take a perspective on the future direction and remaining challenges of MSNs in the biomedical field.

BackgroundFreezing of gait (FOG) is one of the most disabling gait disturbances in Parkinson’s disease (PD), affecting mobility and balance severely, thereby leading to an increased risk of falls.ObjectivesThe purpose of this systematic review and meta-analysis was to investigate the effects of transcranial magnetic stimulation on FOG in PD.MethodsBased on PRISMA guidelines, we searched the databases of MEDLINE (PubMed), Cochrane Library, PEDro, Embase, and Web of Science. Studies of the English language published up to July 2023 were searched. We retrieved for studies of randomized controlled trials (RCTs) of transcranial magnetic stimulation to treat FOG after PD and screened by inclusion and exclusion criteria. Risk of bias was assessed using the Cochrane Collaboration’s tool (Revman5.30). Characteristics of RCTs were extracted. The heterogeneity of the trials was measured by I2 statistic. The effect size was expressed by a standardized mean difference (SMD) with a 95% confidence interval (CI).ResultsA total of 488 articles were screened, after screening sixteen RCTs involved in 408 patients were included in the qualitative analysis, and 15 RCTs were included in meta-analysis. The outcome measures included FOG-Q, walking time, TUG, and UPDRS. Six studies used FOG-Q as outcome measure, six studies used walking time, four studies used TUG, and six studies used UPDRS. Compared with placebo treatment, transcranial magnetic stimulation has positive significant effects in improving gait status with increased walking speed (SMD = −0.41, 95% CI = −0.75 to −0.06, I2 = 7% p = 0.02), FOG-Q scores (SMD = −0.55, 95% CI = −0.89 to −0.21, I2 = 29%, p = 0.002), UPDRS scores (SMD = −1.08, 95% CI = −1.39 to −0.78, I2 = 49%, P < 0.001) and the time of TUG (SMD = −0.56, 95% CI = −0.88 to −0.23, I2 = 25%, p = 0.02) decreased.ConclusionTranscranial magnetic stimulation could significantly improving gait conditions in PD patients with FOG.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42023434286.

Abstract Background Atrial fibrillation (AF) predisposes patients to the formation of atrial thrombi. The CHA2DS2-VASc score does not include all risk factors for atrial thrombosis. The present study is designed to explore the influencing factors of thrombus formation in patients with AF and to investigate the effect of catheter ablation (CA) on recurrent thrombosis in patients with a history of intracardiac thrombus. Methods (1) This study consisted of 1726 patients that underwent CA, among which 58 patients had a history of intracardiac thrombus prior to CA. The risk factors for thrombus formation were explored by comparing the baseline clinical characteristics of patients with and without atrial thrombus. (2) The left atrial appendage flow velocity (LAAFV) in patients with a history of intracardiac thrombus who were willing to undergo transesophageal echocardiography (TEE) at the latest follow-up were examined, and comparisons of the LAAFV was made before and after CA. Results The median follow-up period is 13 months. Persistent AF was found to be the only independent risk factor affecting the formation of atrial thrombus among the investigated factors (OR 3.152; 95%CI 1.806–5.500; p

BackgroundThere are very few studies on transcranial magnetic stimulation (TMS) therapy for facial paralysis and no studies comparing the efficacy of central and peripheral TMS in the treatment of peripheral facial paralysis (PFP).PurposeTo observe the therapeutic effect and security of central and peripheral repetitive transcranial magnetic stimulation (rTMS) on PFP.MethodsPatients with unilateral onset of peripheral facial paralysis within 1 month were prospectively recruited, 97 patients with PFP were divided into the peripheral group, central group, and control group. The control group was given common treatment (drug therapy and acupuncture), and the peripheral and central groups received rTMS in addition to conventional treatment. After 2 weeks of treatment, the House-Brackmann (HB) grading scale, Sunnybrook facial grading system (SFGS), and modified Portmann scale (MPS) were used to evaluate the facial muscle function of patients in the three groups.ResultAfter 2 weeks of rTMS treatment, the HBGS/SFGS/MPS scores of the three groups were significantly better than before (p 0.05).ConclusionOur study shows that rTMS can be a safe and effective adjuvant therapy for patients with PFP. Preliminary studies have shown that both peripheral and central stimulation can effectively improve facial nerve function, but there is no significant difference in the efficacy of the two sites.

Background: Alzheimer's disease (AD) is an irreversible and difficult-to-treat neurodegenerative disease. It is necessary to search for reliable biomarkers for the early diagnosis of AD in a timely and effective manner in high-risk or preclinical AD populations. Studies have shown that neurogenic exosomes in the blood can be effectively used as biomarkers for AD. Objective: In this meta-analysis, we aimed to find reliable biomarkers (Aβ42, T-tau, and P-tau181 in peripheral blood neurogenic exosomes) for the early diagnosis of AD to provide theoretical support for the early diagnosis of high-risk or preclinical AD populations. Methods: By searching the literature database, relevant studies on AD diagnostic markers were collected. The study period was from April 1, 2012, to April 1, 2022. The average concentrations of Aβ42, T-tau, and P-tau181 in the exosomes of the AD group and healthy control group were compared using RevMan 5.3 software. Results: A total of 13 studies were screened, including 842 subjects. Meta-analysis showed that the combined SMD value of neurogenic exosome Aβ42 was 1.70 (95% CI = [1.20,2.20], Z = 6.69, P

Abstract Sonodynamic therapy (SDT) has been widely reported as a noninvasive and high‐penetration therapy for cancer; however, the design of an efficient sonosensitizer remains an urgent need. To address this issue, molybdenum disulfide nanoflowers (MoS2 NF) as piezo‐sonosensitizers and introduced sulfur vacancies on the MoS2 NF (Sv‐MoS2 NF) to improve their piezoelectric property for cancer therapy are designed. Under ultrasonic mechanical stress, the Sv‐MoS2 NF resulted in piezoelectric polarization and band tilting, which enhanced the charge carrier separation and migration. This resulted in an improved catalytic reaction for reactive oxygen species (ROS) production, ultimately enhancing the SDT performance. Thanks to the high efficiency of ROS generation, the Sv‐MoS2 NF have demonstrated a good anticancer effect in vitro and in vivo. Following a systematic evaluation, Sv‐MoS2 NF also demonstrated good biocompatibility. This novel piezo‐sonosensitizer and vacancy engineering strategy provides a promising new approach for achieving efficient SDT.

Northern China faces water scarcity, restricting water usage in place across Inner Mongolia’s western region. The integrated irrigation and fertilization model for sugar beet is undergoing rapid development and application in production. However, there is a concerning trend in production where the frequency of irrigation and fertilization is being increased blindly, resulting in the wastage of valuable water and fertilizer resources. Limiting water and fertilizer usage is an effective approach to improve sugar beet production efficiency. Sugar beets are a significant sugar crop in China. A split-plot design was employed to examine the impact of reducing water and fertilizer use on sucrose metabolism in sugar beet root. Our study was performed at the Ulanqab Institute of Agricultural and Forestry Sciences in Inner Mongolia from 2022 to 2023. Three levels of fertilization and irrigation were utilized. We investigated the interactions between irrigation and fertilization on sucrose accumulation in sugar beet root. We examined key enzyme activities involved in sucrose metabolism alongside their gene expression levels. The findings suggested that reducing irrigation by 15%, fertilization by 10%, or both irrigation by 15% and fertilization by 10%, increased sucrose concentrations of sugar beets compared to the control group administered conventional water and fertilizer. Over the two-year period, the average sucrose concentration increased by 0.45, 0.57, and 0.65 degrees, respectively, under each treatment. Subsequent research verified that appropriately reducing water and fertilizer can regulate the expression of enzyme genes, thus influencing enzyme activity. Moreover, due to the higher efficiency of enzyme synthesis compared to decomposition, it contributed to an increase in net enzyme activity. These findings suggest that an appropriate reduction of water and fertilizer can improve sucrose synthesis rates and increase the sucrose concentration in sugar beets, providing a theoretical basis for environmentally friendly generation and enhanced efficiency in sugar beet growth.

Background: The prevalence of swallowing disorders in Parkinson’s disease (PD) is relatively high. Different physiotherapy interventions for swallowing disorders are available but there is a lack of evidence-based medicine for their effectiveness in PD. Objective: The purpose of this systematic review was to investigate the effects of different physiotherapy interventions on dysphagia in PD. Methods: This systematic review was conducted according to PRISMA guidelines. We methodically searched databases including PubMed, PEDro, Cochrane Library, Embase, and Web of Science. Studies of any language published up to March 2022 were searched. Randomized controlled trials (RCTs) of non-pharmacological treatment for dysphagia in PD were selected in strict accordance with our exclusion and inclusion criteria. Results: In total, we identified and included 10 RCTs in patients with PD undergoing dysphagia. This review involved seven rehabilitation treatments, including acupuncture, expiratory muscle strength training (EMST), repetitive transcranial magnetic stimulation (rTMS), video-assisted swallowing therapy (VAST), electrical stimulation, and speech and language therapy (SLT). Conclusion: For physiotherapy treatments, including acupuncture, EMST, high-frequency rTMS and VAST may be effective treatments for dysphagia in patients with PD. However, there was not enough evidence that electrical stimulation has therapeutic effects on dysphagia in patients with PD.

Despite numerous studies on the response of vegetation change to climate variation, they have mainly been based on annual mean temperature and annual mean precipitation, and have failed to reveal the impact of climate on the inter-annual variation of vegetation in different geomorphic zones based on non-linear methods and considering daily low and high temperature. In this study, the effect of climate variation on the inter-annual variation of vegetation in different geomorphic zones along the area of t the Yangtze River Basin, China from 1982 to 2015 is revealed using Ensemble Empirical Mode Decomposition method. The results show that the inter-annual variation of vegetation is frequently fluctuating, mainly on a short time scale (3-year time scale), and its contribution gradually increases from 62.35% to 73.57% with increasing relief (from plain to high undulating mountain). The vegetation change of more than 75% of the areas is dominated by inter-annual variations, moreover, the vegetation change of the low relief areas is dominated by the 3-year timescale along with the long-term trend, while that of the other geomorphic zones is dominated by the 3-year timescale only. Inter-annual vegetation variation is positively related to precipitation and maximum temperature, but negatively related to mean temperature and minimum temperature in most areas, with area percentages of 67.20%, 86.55%, 65.38% and 75.02%. Inter-annual variation is mainly controlled by maximum temperature in most areas (54.77%). These results will deepen our understanding of the vegetation-climate relationship, suggesting that the responses of inter-annual variation in vegetation to climate vary not only on different time scales, but also in indifferent geomorphic zones.

Metal-organic frameworks (MOFs) are promising nanoporous materials with diverse applications. Traditional material discovery based on intensive manual experiments has certain limitations on efficiency and effectiveness when faced with nearly infinite material space. The current situation offers an opportunity for high-throughput (HT) and machine learning (ML) approaches, including computational and experimental methods, as they have greatly improved the efficiency of MOF screening and discovery and have the capacity to deal with the enormous growth of data. In this review, we discuss the research progress in HT computation and experiments and their effect on MOF screening and discovery. We also highlight how ML-based approaches and the integration of HT methods with ML algorithms accelerate MOF design. In addition, we provide our insights on the future capability of data-driven techniques for MOF discovery, despite facing some knowledge gaps as an obstacle.

Pathogenic bacteria pose a devastating threat to public health. However, because of the growing bacterial antibiotic resistance, there is an urgent need to develop alternative antibacterial strategies to the established antibiotics. Herein, iron-doped carbon dots (Fe-CDs, ∼3 nm) nanozymes with excellent photothermal conversion and photoenhanced enzyme-like properties are developed through a facile one-pot pyrolysis approach for synergistic efficient antibacterial therapy and wound healing. In particular, Fe doping endows CDs with photoenhanced peroxidase (POD)-like activity, which lead to the generation of heat and reactive oxygen species (ROS) for Gram-positive and Gram-negative bacteria killing. This study demonstrates Fe-CDs have significant wound healing efficiency of Fe-CDs by preventing infection, promoting fibroblast proliferation, angiogenesis, and collagen deposition. Furthermore, the ultrasmall size of Fe-CDs possesses good biocompatibility favoring clinical translation. We believe that the nanozyme-mediated therapeutic platform presented here is expected to show promising applications in antibacterial.

Intercropping cereals and legumes is practiced widely in the world for improving yields and economic benefits. Shorter legume crops in intercropping are shaded by taller cereals, substantially reducing legume growth and yield. Reducing shade in intercropping by shortening the plant height of cereals by seedling defoliation has been proposed as a practical approach to increase crop yields and land productivity. A two-year field experiment was conducted to investigate the effect of defoliation of cereal crops at seedling stage on the growth and yield of peanut (Arachis hypogaea L.) intercropped with corn (Zea mays L.) or millet (Setaria italica L.). In comparison with non-defoliation controls, defoliation reduced final plant height by 29 cm on average for corn and 18 cm for millet. Photosynthetically active radiation on peanut in intercropping systems with corn or millet intercropping was respectively 27.0% and 22.8% higher than those in controls, significantly improving the light environment of intercropped peanut. Net photosynthetic rates of peanut were on average 25.5% higher in corn and peanut intercropping and 19.6% higher in millet and peanut intercropping than those in non-defoliation controls. Total biomass of intercropped peanut increased owing to increased root growth. Across two years, yield of peanut intercropped with corn was 27.7% and with millet 32.8% higher than those of controls. Defoliation of cereal crops did not affect corn yield but significantly decreased millet yield by 24.5%. Our results suggest that applying seedling defoliation in intercropped corn could increase peanut yield without compromising corn yield in an intercropping system.

Abstract Phototherapy, mainly including photothermal therapy (PTT) and photodynamic therapy (PDT), can kill cancer cells by generating heat or reactive oxygen species, which has the advantages of being minimally invasive, high efficiency, and low toxicity. However, traditional phototherapeutic agents face challenges such as poor tumor targeting, susceptibility to passive immune clearance, and suboptimal biocompatibility, which limit their clinical application. Recently, cell membrane biomimetic technology endows phototherapeutic agents with unique biological functions, such as promoted immune escape, prolonged in vivo circulation time, improved biocompatibility, and enhanced anti‐tumor efficacy. In addition, phototherapy mediated by cancer cell membrane (CCM) or immune cell membrane‐modified phototherapeutic agents can promote broad anti‐tumor immunity. In this review, we deeply analyze the mechanisms of PTT and PDT, systematically discuss the synthesis strategies and biological functions of cell membrane biomimetic nanomaterials, and focus on the progress of phototherapy based on biomimetic nanomaterials and synergistic therapies such as chemotherapy, radiotherapy, immunotherapy, and sonodynamic therapy. Finally, we address the opportunities and future prospects of biomimetic nanomaterials in the field of cancer phototherapy. This comprehensive review is expected to provide insights into promoting the clinical translation of biomimetic phototherapeutic agents.

Abstract Recently, variable nanocatalysts have provided novel, highly selective, minimally invasive strategies driven by external physical fields for cancer therapy. In the catalytic reaction, less toxic or nontoxic substances can be in situ converted into toxic agents for cancer suppression. In this review, we systematically summarize the catalytic cancer therapy based on different types of external physical fields, including light, ultrasound, electricity, temperature, X‐ray, magnetic field, and microwave. The properties, mechanisms, and advantages of the corresponding external physical fields in cancer therapy are also introduced. Importantly, considering the rapid development of catalytic nanomedicine, the research progress of catalytic cancer therapy driven by external physical fields is discussed. Finally, the remaining challenges and outlooks that catalytic cancer therapy faced are also outlined. We believe that the emerging external physical fields‐driven nanocatalytic cancer therapy will provide a new avenue for cancer treatment.

Land use changes are thought to deeply impact the changes of terrestrial carbon sink, however, how the changes of land use pattern affect the carbon sink remains unclear. To investigate the response of Net Ecosystem Productivity (NEP) to the pattern of land use dynamics in China, a landscape pattern approach (with the 30 km moving window) was used to analyze the pattern dynamics with continuous Land Use and Land Cover Change (LUCC) data from 1981 to 2019 and the nonlinear trends of the NEP and the patterns of land use were explored from 1981 to 2019 using Ensemble empirical modal decomposition (EEMD) methods, and their interannual relationship was further explored using Pearson correlation. The results are as follows: (1) For NEP, nearly half of the regions did not experience significant changes. 90 %) have experienced significant changes in land use patterns, the fragmentation and shape complexity, diversity and evenness of land use types has increased, while the connection decreased, meanwhile, most of these changes are not monotonical, but experiencing trend shifts; (3) In most of the total area (>80 %), land use patterns showed insignificant relationship with NEP, especially in Qinghai-Tibetan Plateau. However, in Greater Khingan Range, Loess Plateau and southern Hilly area, it showed significant relationship with NEP. Our studies highlight the importance of nonlinear analysis for fully understanding the spatial–temporal changes of NEP and land use patterns, and deepened the understanding the impacts of land use changes on NEP.

BackgroundNeck pain (NP), one of the most common musculoskeletal diseases, exercises a great influence on the daily life of individuals, especially the elderly. Baduanjin is a traditional Qigong therapy from China, but there is no evidence for its use in the treatment of neck pain in middle-aged and elderly people.ObjectiveWe hope to summarize the efficacy evidence of Baduanjin in the treatment of middle-aged and elderly patients with neck pain (NP) for the first time, conduct a systematic review and meta-analysis, and provide basic evidence-based evidence for clinical practice.MethodsTwo researchers collectively searched PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disk (Sino-Med), China National Knowledge Infrastructure (CNKI), Wanfang database, and China Science and Technology Journal Database (VIP). The search time is set from initial to 27 September 2022, to find out RCT articles that may meet the criteria. The risk bias assessment tool Cochrane was applied to assess the methodological quality of involved studies. RevMan 5.3 was used for the meta-analysis with a mean difference (MD) and 95% confidence interval (CI), and the model type was a random effects model. The VAS scores of the intervention and control groups were extracted and the results of the meta-analysis were presented using a forest plot.ResultsIn total, 13 randomized controlled trials were meta-analyzed, including 840 patients. The results turned out that the VAS score in the intervention group was below the control group, which was statistically significant [MD = −1.15, 95% CI (−1.39, −0.92) and P < 0. 001]. The result of general efficiency suggests that the Baduanjin group was better than the control group [RR = 1.19, 95% CI (1.10, 1.29), P < 0.001].ConclusionThe existing results seem to show that Baduanjin is safe and has a trend of positive benefits in the treatment of neck pain in middle-aged and elderly people. However, considering the limitations of this study, we need to be cautious in our conclusions, and more studies are needed to verify it in future.

Degradation of crop straw in natural environment has been a bottleneck. There has been a recent increase in the exploration of cold-adapted microorganisms as they can solve the problem of corn straw degradation under low temperatures and offer new alternatives for the sustainable development of agriculture. The study was conducted in low-temperature (10°C) and high-efficiency cellulose-degrading bacteria were screened using carboxymethyl cellulose (CMC) selection medium and subjected to genome sequencing by the third-generation Pacbio Sequl and the second-generation Illumina Novaseq platform, and their cellulase activity was detected by 3,5-dinitrosalicylic acid (DNS) method. The results showed that the low-temperature (10°C) and high-efficiency cellulose-degrading bacterium Bacillus subtilis K1 was 4,060,823 bp in genome size, containing 4,213 genes, with 3,665, 3,656, 2,755, 3,240, 1,261, 3,336 and 4,003 genes annotated in the non-redundant protein sequence database (NR), Pfam, clusters of orthologous groups of proteins (COGs), Genome Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Annotation databases, respectively. In addition, a large number of lignocellulose degradation-related genes were annotated in the genome. The cellulose activity of B. subtilis K1 was higher, exhibiting the highest activity of endo-β-glucanase (24.69 U/ml), exo-β-glucanase (1.72 U/ml) and β-glucosaccharase (1.14 U/ml). It was found that through adding cold-adapted cellulose-degrading bacteriaK1 in the corn straw composting under 6°C (ambient temperature), the average temperature of straw composting was 58.7°C, and higher 86.7% as compared to control. The HA/FA was higher 94.02% than the control and the lignocellulose degradation rate was lower 18.01–41.39% than the control. The results provide a theoretical basis for clarifying the degradation potential of cold-adapted cellulose-degrading bacteria and improving the cellulose degradation efficiency.

BackgroundPrevious studies have shown that cognitive impairment is common after stroke. Transcranial direct current stimulation (tDCS) is a promising tool for rehabilitating cognitive impairment. This study aimed to investigate the effects of tDCS on the rehabilitation of cognitive impairment in patients with stroke.MethodsTwenty-two mild–moderate post-stroke patients with cognitive impairments were treated with 14 tDCS sessions. A total of 14 healthy individuals were included in the control group. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Cortical activation was assessed using functional near-infrared spectroscopy (fNIRS) during the verbal fluency task (VFT).ResultsThe cognitive function of patients with stroke, as assessed by the MMSE and MoCA scores, was lower than that of healthy individuals but improved after tDCS. The cortical activation of patients with stroke was lower than that of healthy individuals in the left superior temporal cortex (lSTC), right superior temporal cortex (rSTC), right dorsolateral prefrontal cortex (rDLPFC), right ventrolateral prefrontal cortex (rVLPFC), and left ventrolateral prefrontal cortex (lVLPFC) cortical regions. Cortical activation increased in the lSTC cortex after tDCS. The functional connectivity (FC) between the cerebral hemispheres of patients with stroke was lower than that of healthy individuals but increased after tDCS.ConclusionThe cognitive and brain functions of patients with mild-to-moderate stroke were damaged but recovered to a degree after tDCS. Increased cortical activation and increased FC between the bilateral cerebral hemispheres measured by fNIRS are promising biomarkers to assess the effectiveness of tDCS in stroke.

Synthetic aperture radar (SAR) and optical images often present different geometric structures and texture features for the same ground object. Through the fusion of SAR and optical images, it can effectively integrate their complementary information, thus better meeting the requirements of remote sensing applications, such as target recognition, classification, and change detection, so as to realize the collaborative utilization of multi-modal images. In order to select appropriate methods to achieve high-quality fusion of SAR and optical images, this paper conducts a systematic review of current pixel-level fusion algorithms for SAR and optical image fusion. Subsequently, eleven representative fusion methods, including component substitution methods (CS), multiscale decomposition methods (MSD), and model-based methods, are chosen for a comparative analysis. In the experiment, we produce a high-resolution SAR and optical image fusion dataset (named YYX-OPT-SAR) covering three different types of scenes, including urban, suburban, and mountain. This dataset and a publicly available medium-resolution dataset are used to evaluate these fusion methods based on three different kinds of evaluation criteria: visual evaluation, objective image quality metrics, and classification accuracy. In terms of the evaluation using image quality metrics, the experimental results show that MSD methods can effectively avoid the negative effects of SAR image shadows on the corresponding area of the fusion result compared with CS methods, while model-based methods exhibit relatively poor performance. Among all of the fusion methods involved in the comparison, the non-subsampled contourlet transform method (NSCT) presents the best fusion results. In the evaluation using image classification, most experimental results show that the overall classification accuracy after fusion is better than that before fusion. This indicates that optical-SAR fusion can improve land classification, with the gradient transfer fusion method (GTF) yielding the best classification results among all of these fusion methods.

Delay and jitter sensitive industrial control and remote driving application-driven network by best-effort to deterministic service.To meet the deterministic application of delay and jitter demands, industry and academia have conducted detailed research on stream filtering shaping and queue forwarding control, implementing microsecond delay and microsecond jitter of light load steady in small-scale ethernet environment.However, the study seldom considers the effects of long-distance topology change, transmission delay fluctuations and short-time traffic overloads, challenging to meet deterministic requirements under large-scale backbone networks.For this challenge, based on cyclic queuing and forwarding, considers source-destination path properties and deterministic traffic intensity, the global cyclic queuing and forwarding three-queue was proposed.The deterministic network simulation system was based on OMNeT++.Experiments compare queue forwarding control mechanisms such as CQF, CQF-three and GCQF-three.Results show that GCQF-three can timely adjust the gatecontrol and queueing priority according to the deterministic traffic state, achieves the best in delay, jitter and network utilization.

The preparation of nanocages with unprecedented architectures may lead to new functions. Here the authors report the self-assembly of organic cages featuring twin cavities; the geometry and pocket size determine the molecular packing and the proton conductivity performance.

BackgroundAngiogenesis and remodeling (AR) is necessary for the growth and metastasis of cancers. Although AR related genes involved in this process are reported, the correlation between AR and clinical outcome, immune cell infiltration, and immunotherapy is still unknown in diverse cancers. This study aimed to investigate the role of AR in the tumor immune microenvironment (TIME) in pan-cancer, and explore its values in prognostic prediction and therapeutic responses.MethodsFirstly, AR genes (including angiogenesis genes and blood vessel remodeling genes) are collected from MsigDB database. The differential expression, and prognostic value of AR genes were studied in 33 tumor types based on TCGA and GTEx data. The AR score of each sample was calculated using the “ssGSEA” function of R package “GSVA” in pan-cancer. The correlation of the AR score with TIME index, such as the amount of stromal and immune components and the immune cell infiltration, was evaluated via integrating multiple computational methods. And we also utilized IMvigor210 and GSE78220 data to explore the prediction value of the AR score on the immunotherapy response.ResultsSignificant differences in AR gene expression between tumors and adjacent normal tissues were found in most cancer types. The AR score varied depending on the types of tumors, and high score was related to worse survival in various tumors, such as pancreatic and stomach adenocarcinoma and so on. Moreover, the AR score was further explored to be positively correlated with proportions and pathways of immune and stromal in TIME. And the AR score was positively correlated with immunosuppressive cells, including TAMs and iTregs, while negatively with CD8+ T cells. Further analysis revealed that patients with high AR had worse therapy efficacy and survival status in bladder cancer and melanomas.ConclusionsOur systematic analysis revealed that AR is closely associated TIME, and prognosis, and clinical characteristics in multiple cancers. Targeting AR genes may activate immune microenvironment and increase the efficacy of immunotherapy.

BackgroundAcetaldehyde dehydrogenase 2 (ALDH2) is an essential enzyme in alcohol metabolism, playing a vital function in resisting oxidative stress. Lots of gene variants have been associated with atrial fibrillation (AF), among which the association between ALDH2 rs671 polymorphism and AF is variable. This study aimed to investigate the relationship between ALDH2 rs671 polymorphism and AF occurrence or progression and AF recurrence after catheter ablation.MethodsA total of 924 subjects were enrolled in the study. The ALDH2 genotypes are composed of wild-type homozygotes (ALDH2*1/*1), heterozygotes (ALDH2*1/*2), and mutant homozygotes (ALDH2*2/*2), in which the genotypes ALDH2*1/*2 and ALDH2*2/*2 are combined into the ALDH2*2. Univariate and multivariate logistic regression analyses were performed to investigate the association between ALDH2*2 and AF occurrence and progression. COX regression analysis was used to explore the association of ALDH2*2 with AF recurrence after catheter ablation.ResultsThe prevalence of AF differed significantly between the ALDH2*2 group (102/251) and ALDH2*1/*1 group (330/673) (P = 0.023). For AF occurrence, in the univariate analysis, alcohol consumption was a risk factors (OR: 1.503, P = 0.003), whereas ALDH2*2 was a protective factor (OR: 0.712, P = 0.023). In the multivariate analysis, alcohol consumption (P = 0.156) and ALDH2*2 (P = 0.096) were no longer independent factors. ALDH2*2 with non-drinking was associated with a decreased AF occurrence (OR: 0.65, P = 0.021), whereas ALDH2*2 with drinking was not (P = 0.365). For AF progression, multivariate analysis revealed ALDH2*2 could promote persistent AF in female AF patients (OR: 2.643, P = 0.008). Cox regression analysis suggested that ALDH2*2 (P = 0.752) was not a risk factor for AF recurrence after catheter ablation during a median 6 months follow-up.ConclusionWhile ALDH2*2 was not directly related to AF, ALDH2*2 with non-drinking was associated with a decreased incidence of AF. ALDH2*2 may accelerate AF progression in female patients, increasing the likelihood of developing persistent AF. Therefore, individuals with ALDH2*2 should refrain from consuming alcohol to decrease the onset and progression of AF.

BackgroundAt present, catheter ablation is an effective method for rhythm control in patients with atrial fibrillation (AF). However, AF recurrence is an inevitable problem after catheter ablation. To identify patients who are prone to relapse, we developed a predictive model that allows clinicians to closely monitor these patients and treat them with different personalized treatment plans.Materials and methodsA total of 1,065 patients who underwent AF catheter ablation between January 2015 and December 2018 were consecutively included in this study, which examines the results of a 2-year follow-up. Patients with AF were divided into development cohort and validation cohort. Univariate and multivariate analyses were carried out on the potential risk factors. Specific risk factors were used to draw the nomogram according to the above results. Finally, we verified the performance of our model compared with CHADS2 and CHA2DS2-Vasc scores by receiver operating characteristic (ROC) curve and calibration curve and plotted the decision analysis curve (DAC).ResultsA total of 316 patients experienced AF recurrence. After univariate and multivariate analyses, AF history (H), age (A), snoring (S), body mass index (BMI) (B), anteroposterior diameter of left atrial (LA) (L), and persistent AF (P) were included in our prediction model. Our model showed a better performance compared with CHADS2 and CHA2DS2-Vasc scores, and the area under ROC curve (95%CI) was 0.7668 (0.7298–0.8037) vs. 0.6225 (0.5783–0.6666) and 0.6267 (0.5836–0.6717).ConclusionWe established a nomogram (HASBLP score) for predicting AF recurrence after the first catheter ablation at a 2-year follow-up, which can be used as a tool to guide future follow-up of patients. However, its usefulness needs further validation.

BackgroundSleep efficiency of

Abstract Biological applications of nanomaterials as delivery carriers have been embedded in traditional biomedical research for decades. Despite lagging behind, recent significant breakthroughs in the use of nanocarriers as tools for plant biotechnology have created great interest. In this Perspective, we review the outstanding recent works in nanocarrier‐mediated plant transformation and its agricultural applications. We analyze the chemical and physical properties of nanocarriers determining their uptake efficiency and transport throughout the plant body.

ObjectiveOur study aims to measure the cortical correlates of swallowing execution in patients with dysphagia after repetitive transcranial magnetic stimulation (rTMS) therapy using functional near-infrared spectroscopy (fNIRS), and observe the change of pattern of brain activation in stroke patients with dysphagia after rTMS intervention. In addition, we tried to analyze the effect of rTMS on brain activation in dysphagia patients with different lesion sides. This study also concentrated on the effect of stimulating the affected mylohyoid cortical region by 5 Hz rTMS, providing clinical evidence for rTMS therapy of dysphagia in stroke patients.MethodsThis study was a sham-controlled, single-blind, randomized controlled study with a blinded observer. A total of 49 patients completed the study, which was randomized to the rTMS group (n = 23) and sham rTMS group (n = 26) by the random number table method. The rTMS group received 5 Hz rTMS stimulation to the affected mylohyoid cortical region of the brain and the sham rTMS group underwent rTMS using the same parameters as the rTMS group, except for the position of the coil. Each patient received 2 weeks of stimulation followed by conventional swallowing therapy. Standardized Swallowing Assessment (SSA), Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), Penetration-Aspiration Scale (PAS), and functional oral intake status were assessed at two times: baseline (before treatment) and 2 weeks (after intervention). Meanwhile, we use the fNIRS system to measure the cerebral hemodynamic changes during the experimental procedure.ResultsThe rTMS group exhibited significant improvement in the SSA scale, FEDSS scale, and PAS scale after rTMS therapy (all P < 0.001). The sham rTMS group had the same analysis on the same scales (all P < 0.001). There was no significant difference observed in clinical assessments at 2 weeks after baseline between the rTMS group and sham rTMS group (all P > 0.05). However, there were statistically significant differences between the two groups in the rate of change in the FEDSS score (P = 0.018) and PAS score (P = 0.004), except for the SSA score (P = 0.067). As for the removal rate of the feeding tube, there was no significant difference between the rTMS group and sham rTMS group (P = 0.355), but there was a significant difference compared with the baseline characteristics in both groups (PrTMS < 0.001, PshamrTMS = 0.002). In fNIRS analysis, the block average result showed differences in brain areas RPFC (right prefrontal cortex) and RMC (right motor cortex) significantly between the rTMS group and sham rTMS group after intervention (Pchannel30 = 0.046, Pchannel16 = 0.006). In the subgroup analysis, rTMS group was divided into left-rTMS group and right-rTMS group and sham rTMS group was divided into sham left-rTMS group and sham right-rTMS group. The fNIRS results showed no significance in block average and block differential after intervention between the left-rTMS group and sham left-rTMS group, but differences were statistically significant between the right-rTMS group and sham right-rTMS group in block average: channel 30 (T = −2.34, P = 0.028) in LPFC (left prefrontal cortex) and 16 (T = 2.54, P = 0.018) in RMC. After intervention, there was no significance in left-rTMS group compared with baseline, but in right-rTMS group, channel 27 (T = 2.18, P = 0.039) in LPFC and 47 (T = 2.17, P = 0.039) in RPFC had significance in block differential. In the sham rTMS group, neither sham left-rTMS group and sham right-rTMS group had significant differences in block average and block differential in each brain area after intervention (P > 0.05).ConclusionsThe present study confirmed that a 5-Hz rTMS is feasible at the affected mylohyoid cortical region in post-stroke patients with dysphagia and rTMS therapy can alter cortical excitability. Based on previous studies, there is a dominant hemisphere in swallowing and the results of our fNIRS analysis seemed to show a better increase in cortical activation on the right side than on the left after rTMS of the affected mylohyoid cortical region. However, there was no difference between the left and right hemispheres in the subgroup analysis. Nevertheless, the present study provides a novel and feasible method of applying fNIRS to assessment in stroke patients with dysphagia.

ObjectiveThis study aimed to examine the effectiveness and safety of the Brain-computer interface (BCI) in treatment of upper limb dysfunction after stroke.MethodsEnglish and Chinese electronic databases were searched up to July 2021. Randomized controlled trials (RCTs) were eligible. The methodological quality was assessed using Cochrane’s risk-of-bias tool. Meta-analysis was performed using RevMan 5.4.ResultsA total of 488 patients from 16 RCTs were included. The results showed that (1) the meta-analysis of BCI-combined treatment on the improvement of the upper limb function showed statistical significance [standardized mean difference (SMD): 0.53, 95% CI: 0.26–0.80, P < 0.05]; (2) BCI treatment can improve the abilities of daily living of patients after stroke, and the analysis results are statistically significant (SMD: 1.67, 95% CI: 0.61–2.74, P < 0.05); and (3) the BCI-combined therapy was not statistically significant for the analysis of the Modified Ashworth Scale (MAS) (SMD: −0.10, 95% CI: −0.50 to 0.30, P = 0.61).ConclusionThe meta-analysis indicates that the BCI therapy or BCI combined with other therapies such as conventional rehabilitation training and motor imagery training can improve upper limb dysfunction after stroke and enhance the quality of daily life.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) applied to the mylohyoid cortical region has positive clinical effects on post-stroke. Therefore, we conducted a meta-analysis to investigate the efficacy of rTMS for patients with post-stroke dysphagia.MethodsAccording to PRISMA guidelines, we searched the databases of MEDLINE (PubMed), Cochrane Library, Embase, Web of Science, CNKI, Wangfang. We searched for studies of randomized controlled trials (RCTs) of rTMS to treat dysphagia after stroke and screened by inclusion and exclusion criteria. Features of RCTs were extracted. The heterogeneity of the trials was measured by I2 statistic.ResultsIn total, 11 RCTs with 463 dysphagia patients fulfilled our inclusion criteria. In our analysis, rTMS demonstrated a great beneficial effect for post-stroke dysphagia when combined with traditional swallowing exercises. Moreover, a greatly significant difference (P = 0.008) was noted based on stimulation frequency (high frequency vs. low frequency). Additionally, no significant difference (P = 0.53) was observed based on stimulation site (affected vs. unaffected hemisphere).ConclusionsOverall, rTMS can effectively accelerate the improvement of swallowing function in patients with post-stroke swallowing disorders.

Although 17β-estradiol (E2) can be locally synthesized in the brain, whether and how brain-derived E2 (BDE2) impacts neurogenesis with aging is largely unclear. In this study, we examined the hippocampal neural stem cells, neurogenesis, and gliogenesis of 1, 3, 6, 14, and 18-month (Mon) female rats. Female forebrain neuronal aromatase knockout (FBN-ARO-KO) rats and letrozole-treated rats were also employed. We demonstraed that (1) the number of neural stem cells declined over 14-Mon age, and the differentiation of astrocytes and microglia markedly elevated and exhibited excessive activation. KO rats showed declines in astrocyte A2 subtype and elevation in A1 subtype at 18 Mon; (2) neurogenesis sharply dropped from 1-Mon age; (3) KO suppressed dentate gyrus (DG) neurogenesis at 1, 6 and 18 Mon. Additionally, KO and letrozole treatment led to declined neurogenesis at 1-Mon age, compared to age-matched WT controls; (4) FBN-ARO-KO inhibited CREB-BDNF activation, and decreased protein levels of neurofilament, spinophilin and PSD95. Notably, hippocampal-dependent spatial learning and memory was impaired in juvenile (1 Mon) and adulthood (6 Mon) KO rats. Taken together, we demonstrated that BDE2 plays a pivotal role for hippocampal neurogenesis, as well as learning and memory during female aging, especially in juvenile and middle age.

Considering the embarrassments related to inadequate safety monitoring detection and chaotic development order during the current ecological development of coastal tidal mudflat, we put forward a remote sensing image-based comprehensive monitoring detection platform integrating image data acquisition, mechanism analysis, comprehensive evaluation, and intelligent monitoring detection for coastal tidal mudflat ecological development. The platform includes imaging and data fusion technology, comprehensive evaluation and spatial layout optimization technology, and dynamic safety monitoring and early warning technology. A case study on Dafeng coastal tidal mudflat was conducted. The results show that our research can provide substantial reference for the coordination, dynamic management, and comprehensive regulation for the ecological development of coastal tidal mudflat.

Background. Rehabilitation of upper extremity hemiplegia after stroke remains a great clinical challenge, with only 20% of patients achieving a basic return to normal hand function. How to promote the recovery of motor function at an early stage is crucial to the life of the patient. Objectives. To invest the effects of additional mirror therapy in improving upper limb motor function and activities of daily living in acute and subacute stroke patients, and further explore the effects of other factors on the efficacy of MT. Methods. Participants who presented with unilateral upper extremity paralysis due to a first ischemic or hemorrhagic stroke were included in the study. They were randomly allocated to the experimental or control group. Patients in the control group received occupational therapy for 30 minutes each session, six times a week, for three weeks, while patients in the experimental group received 30 minutes of additional mirror therapy based on occupational therapy. The primary outcome measures were Fugl-Meyer Assessment—upper extremity (FMA-UE), Action Research Arm Test (ARAT), and Instrumental Activity of Daily Living (IADL) which were evaluated by two independent occupational therapists before treatment and after 3-week treatment. A paired t-test was used to compare the values between pretreatment and posttreatment within an individual group. Two-sample t-test was utilized to compare the changes (baseline to postintervention) between the two groups. Results. A total of 52 stroke patients with unilateral upper extremity motor dysfunction who were able to actively cooperate with the training were included in this study. At baseline, no significant differences were found between groups regarding demographic and clinical characteristics (P>0.05 for all). Upper limb motor function and ability to perform activities of daily living of the patients were statistically improved in both groups towards the third week (P0.05). The subgroup analysis showed that no significant heterogeneity was observed in age, stroke type, lesion side, and clinical stage (P>0.05). Conclusion. In conclusion, some positive changes in aspects of upper limb motor function and the ability to perform instrumental activities of daily living compared with routine occupational therapy were observed in additional mirror therapy. Therefore, the application of additional mirror therapy training should be reconsidered to improve upper extremity motor in stroke patients.

Purpose. The purpose of this study was to evaluate the clinical efficacy of peripheral repetitive transcranial magnetic stimulation (rTMS) in the treatment of idiopathic facial paralysis, to explore an ideal treatment scheme for idiopathic facial paralysis, and to provide evidence for clinical rehabilitation. Methods. 65 patients with idiopathic facial nerve palsy with the first onset were recruited and randomly divided into rTMS group and control group. Both groups received conventional treatment, rTMS group received additional repetitive transcranial magnetic stimulation to the affected side once a day, 5 times a week for 2 weeks. House-Brackmann (HB) grading scale, Sunnybrook facial grading system (SFGS), and modified Portmann scale (MPS) were used to assess facial nerve function before and after treatment, and the time for patients to return to normal facial nerve function and adverse reaction (AR) was also the main observation index. Results. After a 2-week intervention, HB, SFGS, and MPS increased in both groups (P

Background: Pan-renal cell carcinoma (pan-RCC) is mainly divided into renal clear cell carcinoma (KIRC), renal papillary cell carcinoma (KIRP), and chromophobe cell carcinoma (KICH). Pan-RCC is a common malignant neoplasm with a high incidence and poor prognosis. Several studies have demonstrated a close association between cancer development and circadian rhythms; however, the clinical significance and molecular mechanism of the clock gene remain unclear in pan-RCC.Methods: In this study, we systematically characterized the alterations of 15 well-known clock genes of three types of kidney cancer. Bioinformatics methods, including differential expression analysis, survival analysis, signing pathway analysis, co-expression network analysis, and drug sensitivity analysis were used to study the diagnosis, prognostic role, and mechanism of clock genes.Results: Thirteen rhythmic genes fluctuated in circadian rhythm in the kidney tissue of mice, and the opposite trend of these rhythm phases was also found in baboons. There are twelve clock genes that were differentially expressed in at least two types of RCC, of which NR1D1, DBP, BHLHE40, CRY1, and CLOCK had the same trend in RCC. Changes in clock control genes may be regulated through methylation, copy number, and mutations. Five rhythmic genes, including PER2, DBP, PER3, CRY2, and RORA, have significant prognostic role in patient survival in at least two types of kidney cancer. Immune infiltration analysis showed that the expression of these rhythmic genes related to prognosis was positively correlated with the infiltration levels of CD4 and CD8 T cells. Pathway analysis suggests that the clock genes is widely related to cancer-related signaling pathways, such as apoptosis, cell cycle, and other pathways. The PPI network showed that circadian genes are closely linked to cancer-related genes such as HIF-1A, TP53, and ERBB2. Moreover, clock gene expression is correlated with the sensitivity of anticancer drugs such as bleomycin and methotrexate in pan-RCC.Conclusion: Taken together, the abnormal expression of biological clock genes plays an important role in the clinical prognosis of RCC through immunity, cell cycle, and apoptosis. These findings provide a reliable basis for the diagnosis, prognosis, and drug guidance for RCC.

Deep neural networks (DNNs) are one of the key fields of machine learning. It requires considerable computational resources for cognitive tasks. As a novel technology to perform computing inside/near memory units, in-memory computing (IMC) significantly improves computing efficiency by reducing the need for repetitive data transfer between the processing and memory units. However, prior IMC designs mainly focus on the acceleration for DNN inference. DNN training with the IMC hardware has rarely been proposed. The challenges lie in the requirement of DNN training for high precision (e.g. floating point (FP)) and various operations of tensors (e.g. inner and outer products). These challenges call for the IMC design with new features. This paper proposes a novel Hadamard product-based IMC design for FP DNN training. Our design consists of multiple compartments, which are the basic units for the matrix element-wise processing. We also develop BFloat16 post-processing circuits and fused adder trees, laying the foundation for IMC FP processing. Based on the proposed circuit scheme, we reformulate the back-propagation training algorithm for the convenience and efficiency of the IMC execution. The proposed design is implemented with commercial 28 nm technology process design kits and benchmarked with widely used neural networks. We model the influence of the circuit structural design parameters and provide an analysis framework for design space exploration. Our simulation validates that MobileNet training with the proposed IMC scheme saves $91.2\%$ in energy and $13.9\%$ in time versus the same task with NVIDIA GTX 3060 GPU. The proposed IMC design has a data density of 769.2 Kb mm ^−2 with the FP processing circuits included, showing a 3.5 × improvement than the prior FP IMC designs.

Background: Parkinson's disease is a common neurodegenerative disorder with motor and non-motor symptoms. Recently, as adjuvant therapy, transcranial direct current stimulation (tDCS) has been shown to improve the motor and non-motor function of patients with Parkinson's disease (PD). This systematic review aimed to evaluate the existing evidence for the efficacy of tDCS for PD. We included English databases (PubMed, the Cochrane Library, Embase, and Web of Science) and Chinese databases [Wanfang database, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and China Biology Medicine (CBM)] without restricting the year of publication. Twenty-one tDCS studies, with a total of 736 participants, were included in the analysis. Two independent researchers extracted the data and characteristics of each study. There was a significant pooled effect size (−1.29; 95% CI = −1.60, −0.98; p < 0.00001; I2 = 0%) in the Unified PD Rating Scale (UPDRS) I and the Montreal cognitive assessment (SMD = 0.87, 95% CI = 0.50 to 1.24; p < 0.00001; I2 = 0%). The poor effect size was observed in the UPDRS III scores (SMD = −0.13; 95% CI = −0.64, 0.38; p = 0.61; I2 = 77%), and similar results were observed for the timed up and go (TUG) test, Berg balance scale, and gait assessment. The results of this meta-analysis showed that there was insufficient evidence that tDCS improves the motor function of patients with PD. However, tDCS seemed to improve their cognitive performance. Further multicenter research with a larger sample size is needed. In addition, future research should focus on determining the tDCS parameters that are most beneficial to the functional recovery of patients with PD.

Abstract Sonodynamic therapy (SDT) has attracted widespread attention due to its non‐invasiveness and deep tissue penetration. However, the development of efficient sonodynamic nanoplatforms to improve the therapeutic efficiency is still one of the main challenges of current research. In this work, a new type of sonosensitizer prepared by a simple method, manganese carbonate nanoparticles (MnCO3 NPs), is used for enhanced SDT. MnCO3 NPs could generate large amounts of 1O2 and •OH under ultrasound irradiation. At the same time, CO2 and Mn ions could be released in a weak acid environment due to the excellent degradability of MnCO3 NPs. The CO2 bubbles caused cell necrosis by ultrasonic cavitation and used for ultrasound imaging. And Mn ions activated the mitochondrial cell apoptosis pathway. In vivo experiments proved that this sonosensitizer with mitochondrial regulatory capacity showed high tumor inhibition rates for enhanced sonodynamic tumor therapy.

Background: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) protocols on patients with poststroke dysphagia is still unclear.Objective: This trial aimed to explore and analyze the effectiveness of 5 Hz rTMS on the unaffected hemisphere, affected hemisphere, and cerebellum in stroke patients with dysphagia.Methods: This observer-blind and randomized controlled trial included a total of 147 patients with stroke. Patients were divided into four treatment groups: the unaffected hemispheric group, the affected hemispheric group, the cerebellum group and the control group. Each group received traditional dysphagia treatment 5 days a week for 2 weeks. All recruited patients except for those in the control group underwent 10 consecutive rTMS sessions for 2 weeks. For the affected hemispheric group and unaffected hemispheric group, 5 Hz rTMS was applied to the affected mylohyoid cortical region or to the unaffected mylohyoid cortical region. For the cerebellum group, 5 Hz rTMS was applied to the mylohyoid cortical representation of the cerebellum (4.3 cm lateral and 2.4 cm below the inion). The Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), Penetration/Aspiration Scale (PAS), Gugging Swallowing Screen (GUSS), and Standardized Swallowing Assessment (SSA) were used to evaluate clinical swallowing function before the intervention (baseline), immediately after the intervention and 2 weeks after the intervention.Results: There were significant time and intervention interaction effects on the FEDSS, PAS, SSA, and GUSS scores (p < 0.05). In a direct comparison of the swallowing parameters of the four groups, the changes in FEDSS, PAS, SSA, and GUSS scores showed a significantly greater improvement in the unaffected hemispheric group, the affected hemispheric group and cerebellum group than in the control group (p < 0.05).Conclusions: Whether stimulating the unaffected hemisphere or the affected hemisphere, 5 Hz high-frequency rTMS on mylohyoid cortical tissue might have a positive effect on poststroke patients with dysphagia. In addition, cerebellar rTMS is a safe method that represents a potential treatment for poststroke dysphagia, and more clinical trials are needed to develop this technique further.Clinical Trial Registration:chictr.org.cn, identifier: ChiCTR2000032255.

The relationship between vegetation Net primary production (NPP) and climate change is critical for understanding the driving forces of vegetation changes, while less were studied based on detrending analysis and Bioclimatic variables. In this study, detrending analysis based on Ensemble Empirical Mode Decomposition (EEMD) method was adopted to assess the relationship between NPP and climate change in different vegetation zones in Northwest China. The results indicated that: (1) although monotonic increasing was the main type of vegetation NPP trend (49.42%), shifted trend accounted for 36.02% of the whole area. There were some risks of vegetation degradation in temperate desert and alpine region of the Qinghai Tibet Platea, but chances for vegetation recovery in temperate grassland and warm temperate deciduous broad-leaved forest zones; (2) EEMD-detrending analysis performed much better than linear detrending analysis for assessing the relationship between climate change and vegetation NPP; (3) compared with no detrending, EEMD-detrending reduced the importance of BIO1 (annual mean temperature) and BIO2 (mean temperature diurnal range) for vegetation NPP, but enhanced those of BIO13 (precipitation of the wettest month) and BIO15 (precipitation seasonality); (4) BIO1, BIO2, BIO12 (annual precipitation), and BIO13 mainly showed positive relationships with interannual NPP variations, except that BIO1 and BIO13 mainly showed negative relationship in temperate grassland and warm temperate deciduous broad-leaved forest zones. Interannual NPP variations were dominated by BIO12 and BIO13, except that alpine region of Tibet plateau was dominated by BIO1 and BIO2. Our results demonstrated that EEMD-detrending analysis and Bioclimatic variables can better explore the interannual vegetation-climate relationship.

The rate of vegetation green-up (RVG) indicates the ability of vegetation to respond to changes in climatic conditions. Understanding long-term RVG trends can clarify the changes in how quickly the vegetation grows from dormancy to maturity with time. However, how RVG trends respond to environmental variables and variable interactions remains unknown. We examined the long-term RVG trends (1981–2018) over the northern extratropics and determined the influence of environment variables and interactions between variables on the RVG trends based on the Global Land Surface Satellite leaf area index and a multivariable regression considering interactions between variables (MRCI). Our results showed a persistent increase in RVG at 0.020% (8-day)−1 year−1 over the entire region. Except for shrublands (−0.032% (8-day)−1 year−1), RVG trends increased significantly, particularly in woody savannas (0.095% (8-day)−1 year−1) and mixed forests (0.076% (8-day)−1 year−1). The relative importance of interactive effects (RIIAE) to the RVG trends is roughly 30%. Rising CO2, enhanced vapor pressure deficit (VPD), and warming are the primary factors affecting the RVG trends, both at the pixel and the biome scales. The accelerated RVG is triggered by both rising CO2 and warming but is partially offset by increased VPD. Our findings shed light on the relative contribution of variable interactions and assessed the relationship between environmental factors and RVG trends across different biomes, hence strengthening our knowledge of vegetation spring green-up in response to global change.