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Abstract Many plants associate with endophytic microbes that improve root phosphorus (P) uptake. Understanding the interactions between roots and endophytes can enable efforts to improve P utilization. Here, we characterize the interactions between lateral roots of endophytes in a core collection of 50 rapeseed (Brassica napus L.) genotypes with differing sensitivities to low P conditions. With the correlation analysis result between bacterial abundance and plant physiological indices of rapeseeds, and inoculation experiments on plates and soil, we identify one Flavobacterium strain (C2) that significantly alleviates the P deficiency phenotype of rapeseeds. The underlying mechanisms are explored by performing the weighted gene coexpression network analysis (WGCNA), and conducting genome-wide association studies (GWAS) using Flavobacterium abundance as a quantitative trait. Under P-limited conditions, C2 regulates fatty acid and lipid metabolic pathways. For example, C2 improves metabolism of linoleic acid, which mediates root suberin biosynthesis, and enhances P uptake efficiency. In addition, C2 suppresses root jasmonic acid biosynthesis, which depends on α-linolenic acid metabolism, improving C2 colonization and activating P uptake. This study demonstrates that adjusting the endophyte composition can modulate P uptake in B. napus plants, providing a basis for developing agricultural microbial agents.

Abstract Large-scale marine heatwaves in the Northeast Pacific (NEP), identified here and previously as ‘warm blobs’, have devastating impacts on regional ecosystems. An anomalous atmospheric ridge over the NEP is known to be crucial for maintaining these warm blobs, also causing abnormally cold temperatures over North America during the cold season. Previous studies linked this ridge to teleconnections from tropical sea surface temperature anomalies. However, it was unclear whether teleconnections from the extratropics could also contribute to the ridge. Here we show that planetary wave trains, triggered by increased rainfall and latent heat release over the Mediterranean Sea accompanied by decreased rainfall over the North Atlantic, can transport wave energy to the NEP, guided by the westerly jet, and induce a quasi-barotropic ridge there. Our findings provide insights into extratropical teleconnections sustaining the NEP ridge, offering a source of potential predictability for the warm blobs and temperature fluctuations over North America.

Abstract Background A minute fraction of patients stands to derive substantial benefits from immunotherapy, primarily attributable to immune evasion. Our objective was to formulate a predictive signature rooted in genes associated with cytotoxic T lymphocyte evasion (CERGs), with the aim of predicting outcomes and discerning immunotherapeutic response in colorectal cancer (CRC). Methods 101 machine learning algorithm combinations were applied to calculate the CERGs prognostic index (CERPI) under the cross−validation framework, and patients with CRC were separated into high− and low−CERPI groups. Relationship between immune cell infiltration levels, immune−related scores, malignant phenotypes and CERPI were further analyzed. Various machine learning methods were used to identify key genes related to both patient survival and immunotherapy benefits. Expression of HOXC6, G0S2, and MX2 was evaluated and the effects of HOXC6 and G0S2 on the viability and migration of a CRC cell line were in−vitro verified. Results The CERPI demonstrated robust prognostic efficacy in predicting the overall survival of CRC patients, establishing itself as an independent predictor of patient outcomes. The low−CERPI group exhibited elevated levels of immune cell infiltration and lower scores for tumor immune dysfunction and exclusion, indicative of a greater potential benefit from immunotherapy. Moreover, there was a positive correlation between CERPI levels and malignant tumor phenotypes, suggesting that heightened CERPI expression contributes to both the occurrence and progression of tumors. Thirteen key genes were identified, and their expression patterns were scrutinized through the analysis of single−cell datasets. Notably, HOXC6, G0S2, and MX2 exhibited upregulation in both CRC cell lines and tissues. Subsequent knockdown experiments targeting G0S2 and HOXC6 resulted in a significant suppression of CRC cell viability and migration. Conclusion We developed the CERPI for effectively predicting survival and response to immunotherapy in patients, and these results may provide guidance for CRC diagnosis and precise treatment.

Acyl-CoA thioesterase 4 (ACOT4) has been reported to be related to acetyl-CoA carboxylase activity regulation; However, its exact functions in liver lipid and glucose metabolism are still unclear. Here, we discovered explored the regulatory roles of ACOT4 in hepatic lipid and glucose metabolism in vitro. We found that the expression level of ACOT4 was significantly increased in the hepatic of db/db and ob/ob mice as well as obese mice fed a high fat diet. Adenovirus-mediated overexpression of ACOT4 promoted gluconeogenesis and high-glucose/high-insulin-induced lipid accumulation and impaired insulin sensitivity in primary mouse hepatocytes, whereas ACOT4 knockdown notably suppressed gluconeogenesis and decreased the triglycerides accumulation in hepatocytes. Furthermore, ACOT4 knockdown increased insulin-induced phosphorylation of AKT and GSK-3β in primary mouse hepatocytes. Mechanistically, we found that upregulation of ACOT4 expression inhibited AMP-activated protein kinase (AMPK) activity, and its knockdown had the opposite effect. However, activator A769662 and inhibitor compound C of AMPK suppressed the impact of the change in ACOT4 expression on AMPK activity. Our data indicated that ACOT4 is related to hepatic glucose and lipid metabolism, primarily via the regulation of AMPK activity. In conclusion, ACOT4 is a potential target for the therapy of non-alcoholic fatty liver (NAFLD) and type 2 diabetes.

BackgroundAutoimmune nodopathy (AN) has emerged as a novel diagnostic category that is pathologically different from classic chronic inflammatory demyelinating polyneuropathy. Clinical manifestations of AN include sensory or motor neuropathies, sensory ataxia, tremor, and cranial nerve involvement. AN with a serum-positive contactin-1 (CNTN1) antibody usually results in peripheral nerve demyelination. In this study, we reported a rare case of AN with CNTN1 antibodies characterized by the presence of CNTN1 antibodies in both serum and cerebrospinal fluid, which is associated with cerebellar dysarthria.MethodsA 25-year-old man was admitted to our hospital due to progressive dysarthria with limb tremors. The patient was initially diagnosed with peripheral neuropathy at a local hospital. Three years after onset, he was admitted to our hospital due to dysarthria, apparent limb tremor, and limb weakness. At that time, he was diagnosed with spinocerebellar ataxia. Eight years post-onset, during his second admission, his condition had notably deteriorated. His dysarthria had evolved to typical distinctive cerebellar characteristics, such as tremor, loud voice, stress, and interrupted articulation. Additionally, he experienced further progression in limb weakness and developed muscle atrophy in the distal limbs. Magnetic resonance imaging (MRI), nerve conduction studies (NCS), and autoimmune antibody tests were performed.ResultsThe results of the NCS suggested severe demyelination and even axonal damage to the peripheral nerves. MRI scans revealed diffuse thickening of bilateral cervical nerve roots, lumbosacral nerve roots, cauda equina nerve, and multiple intercostal nerve root sheath cysts. Furthermore, anti-CNTN1 antibody titers were 1:10 in the cerebrospinal fluid (CSF) and 1:100 in the serum. After one round of rituximab treatment, the patient showed significant improvement in limb weakness and dysarthria, and the CSF antibodies turned negative.ConclusionApart from peripheral neuropathies, cerebellar dysarthria (central nervous system involvement) should not be ignored in AN patients with CNTN1 antibodies.

ObjectiveMovement disorders (MDs) are common in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis but are poorly studied. This study aimed to investigate the clinical characteristics of MDs and the clinical differences between patients with and without MDs in anti-NMDAR encephalitis.MethodsA retrospective study was conducted on patients with anti-NMDAR encephalitis who were first diagnosed and treated in the First People’s Hospital of Yunnan Province from January 2017 to September 2022. According to the presence or absence of MDs, all patients were divided into two groups, and the clinical manifestations, auxiliary examinations, and prognosis of the two groups were compared. Patients in the MDs group were further subgrouped by different ages (

Abstract Optothermal nanotweezers have emerged as an innovative optical manipulation technique in the past decade, which revolutionized classical optical manipulation by efficiently capturing a broader range of nanoparticles. However, the optothermal temperature field was merely employed for in-situ manipulation of nanoparticles, its potential for identifying bio-nanoparticles remains largely untapped. Hence, based on the synergistic effect of optothermal manipulation and CRIPSR-based bio-detection, we developed CRISPR-powered optothermal nanotweezers (CRONT). Specifically, by harnessing diffusiophoresis and thermo-osmotic flows near the substrate upon optothermal excitation, we successfully trapped and enriched DNA functionalized gold nanoparticles, CRISPR-associated proteins, as well as DNA strands. Remarkably, we built an optothermal scheme for enhancing CRISPR-based single-nucleotide polymorphism (SNP) detection at single molecule level, while also introducing a novel CRISPR methodology for observing nucleotide cleavage. Therefore, this innovative approach has endowed optical tweezers with DNA identification ability in aqueous solution which was unattainable before. With its high specificity and feasibility for in-situ bio-nanoparticle manipulation and identification, CRONT will become a universal tool in point-of-care diagnosis, biophotonics, and bio-nanotechnology.

The existence of ocean currents has a certain impact on the sonar state, torpedoes, and targets during anti-submarine operation. In severe cases, it may even affect the result of the operation. The anti-submarine operation of a surface ship was taken as an example, and a full-process simulation of the anti-submarine combat under various scenarios was carried out to study the influence of ocean currents on the operational effectiveness of anti-submarine. By constructing mathematical models of ocean current, sonar error, torpedo motion, and homing detection error, setting up various scenarios, and employing simulation software, the operation effectiveness of tube-launched anti-submarine torpedoes under different ocean current directions was analyzed. The simulation results show that the current direction during anti-submarine operation in different attack positions has different degrees of influence on the hit probability of the torpedo. When the main heading angle between the current and the torpedo is set between 0° and 90°, the hit probability of the torpedo is greatly improved compared with that in the case of no current. However, when the angle between the current and the torpedo heading is between −180° and 0°, the hit probability of the torpedo is lower than that in the case of no current. Obtaining the current intensity and direction in the operation area can provide support for finely predicting the operation capability of the tube-launched anti-submarine torpedo and optimizing the tube-launched anti-submarine shooting parameters.

With the increasing scale of Electric Vehicles (EVs) connected to the grid, in order to achieve a win–win situation between the grid and Electric Vehicles, it is necessary to consider not only the impact of disordered charging and discharging on the grid load, but also the costs of both sides. This paper establishes an optimal operation model for Electric Vehicles in Electric Power Aggregators (EPAs) based on Stackelberg Game Model. EPA formulates appropriate charge and discharge prices and optimizes scheduling strategies as the upper leader. The lower follower EVs responds optimally to minimize costs. The IEEE33 node system is used to analyze the example, simulation results show that the model not only minimizes the cost of both sides, but also reduces the load power fluctuation due to the large number of Electric Vehicles connected to the grid, and reduces the peak–valley load difference.

Abstract Background Secukinumab has been approved by the U.S. FDA and the European Medicines Agency for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis with the documented adverse effects. Here we reported in one case that a new symptom, Prurigo Nodularis (PN), developed during the programmed dosing of secukinumab. Case introduction A 22-years-old male with a 6-month history of severe plaque psoriasis vulgaris was presented to the dermatology clinic two weeks after the fifth serial weekly doses of secukinumab, for the reason of the outbreaks of multiple erythematous papules and pruritus nodules on the trunk and extremities. Physical examination showed that psoriatic rash were under effective control with the previous targeted therapy of secukinumab for plaque psoriasis vulgaris, but new dermatologic condition was spotted with multiple edematous red firm papules on the trunk and extremities, in the form of soy or hemispherical nodules, red in color, firm to touch, with some ulcerated crusts visible at tops, but negative Auspitz sign. Pathological examination confirmed these papules as PN. Conclusion This case report is shared to inform clinicians about an unannounced adverse effect of the secukinumab in the treatment of psoriasis, and it is recommended that patients be carefully informed of the possible risk of PN before starting treatment.

SPR biosensors have been extensively used for investigating protein–protein interactions. However, in conventional surface plasmon resonance (SPR) biosensors, detection is limited by the Brownian-motion-governed diffusion process of sample molecules in the sensor chip, which makes it challenging to detect biomolecule interactions at ultra-low concentrations. Here, we propose a highly sensitive SPR imaging biosensor which exploits the coffee ring effect (CRE) for in situ enrichment of molecules on the sensing surface. In addition, we designed a wavelength modulation system utilizing two LEDs to reduce the system cost and enhance the detection speed. Furthermore, a detection limit of 213 fM is achieved, which amounts to an approximately 365 times improvement compared to traditional SPR biosensors. With further development, we believe that this SPR imaging system with high sensitivity, less sample consumption, and faster detection speed can be readily applied to ultra-low-concentration molecular detection and interaction analysis.

Abstract Aberrant expression of circular RNAs (circRNAs) has been reported to play an important biological regulatory role in gastric cancer (GC). For the purpose of silencing cancer‐related genes, a new approach for cancer treatment using nanocarriers to deliver siRNA has been proposed. In this study, abundantly expressed circMAP2K2 (hsa_circRNA_102415) is identified in GC cells. CircMAP2K2 regulates the PCBP1/GPX1 axis through proteasome‐mediated degradation, which further mediates the activation of the AKT/GSK3β/epithelial‐to‐mesenchymal transition (EMT) signaling pathway and enhances the proliferation and metastatic ability of GC cells. To establish novel GC treatment, epigallocatechin‐3‐gallate‐lysozyme (EGCG‐LYS) fibrils are synthesized, and in vitro experiments demonstrate that EGCG‐LYS has a higher siRNA delivery efficiency than Lipofectamine 2000 (lipo2000), which effectively silences the expression of circMAP2K2. Further studies show that EGCG‐LYS carrying siRNA can successfully achieve lysosome escape, which allows it to be located in the cytoplasm to achieve post‐transcriptional gene silencing. In addition, EGCG‐LYS carrying si‐circMAP2K2 has good circulating stability, excellent biosafety and antitumor ability in vivo. The EGCG‐LYS fibrils delivery system provides a new tool and approach for the treatment of GC.

Structured illumination microscopy (SIM) is suitable for biological samples because of its relatively low-peak illumination intensity requirement and high imaging speed. The system resolution is affected by two typical detection modes: Point detection and area detection. However, a systematic analysis of the imaging performance of the different detection modes of the system has rarely been conducted. In this study, we compared laser point scanning point detection (PS-PD) and point scanning area detection (PS-AD) imaging in nonconfocal microscopy through theoretical analysis and simulated imaging. The results revealed that the imaging resolutions of PS-PD and PS-AD depend on excitation and emission point spread functions (PSFs), respectively. Especially, we combined the second harmonic generation (SHG) of point detection (P-SHG) and area detection (A-SHG) with SIM to realize a nonlinear SIM-imaging technique that improves the imaging resolution. Moreover, we analytically and experimentally compared the nonlinear SIM performance of P-SHG with that of A-SHG.

Optical tweezers system has emerged as an efficient tool to manipulate tiny particles in a non-invasive way. Trapping stiffness, as an essential parameter of an optical potential well, represents the trapping stability. Additionally, trapping inorganic nanoparticles such as metallic nanoparticles or other functionalized inorganic nanoparticles is important due to their properties of good stability, high conductivity, tolerable toxicity, etc., which makes it an ideal detection strategy for bio-sensing, force calculation, and determination of particle and environmental properties. However, the trapping stiffness measurement (TSM) methods of inorganic nanoparticles have rarely been analyzed and summarized. Here, in this review, the principle and methods of TSM are analyzed. We also systematically summarize the progress in acquiring inorganic particles trapping stiffness and its promising applications. In addition, we provide prospects of the energy and environment applications of optical tweezering technique and TSM. Finally, the challenges and future directions of achieving the nanoparticles trapping stiffness are discussed.

Warm blobs are persistently warmer-than-normal seawaters over the Northeast Pacific (NEP), which cause substantial impacts on marine ecosystems and climate. Recently, the warm blobs occurred consecutively in spring and summer of 2021 and 2022. The warm blob in 2021 was mostly located east of 155°W, while it shifted to west of 155°W in 2022. Based on a mixed-layer heat budget analysis, we find that atmospheric processes positively and dominantly contributed in May 2021 and July 2022. Specifically, less latent heat loss from the ocean caused by reducing background westerlies and evaporation intensified the 2021 warm blob, while more shortwave radiation heating due to decreased low clouds intensified the one in 2022. However, the positive contribution of the atmospheric processes cannot maintain a season due to their strong internal variability. The seasonal persistence of the warm blobs, instead, is owing to the offset between the atmospheric and oceanic processes. We highlight the importance of atmospheric processes in the evolution of the NEP warm blobs in spring and summer, which lacks sufficient investigation but can provide more potential predictability for the NEP warm blobs.

BackgroundMethadone maintenance treatment (MMT) is a common treatment for heroin use disorder (HUD). Although individuals with HUD have been reported to show impaired coupling among the salience network (SN), executive control network (ECN), and default mode network (DMN), the effects of MMT on the coupling among three large-scale networks in individuals with HUD remains unclear.MethodsThirty-seven individuals with HUD undergoing MMT and 57 healthy controls were recruited. The longitudinal one-year follow-up study aimed to evaluate the effects of methadone on anxiety, depression, withdrawal symptoms and craving and number of relapse, and brain function (SN, DMN and bilateral ECN) in relation to heroin dependence. The changes in psychological characteristics and the coupling among large-scale networks after 1 year of MMT were analyzed. The associations between the changes in coupling among large-scale networks and psychological characteristics and the methadone dose were also examined.ResultsAfter 1 year of MMT, individuals with HUD showed a reduction in the withdrawal symptom score. The number of relapses was negatively correlated with the methadone dose over 1 year. The functional connectivity between the medial prefrontal cortex (mPFC) and the left middle temporal gyrus (MTG; both key nodes of the DMN) was increased, and the connectivities between the mPFC and the anterior insular and middle frontal gyrus (key nodes of the SN) were also increased. The mPFC-left MTG connectivity was negatively correlated with the withdrawal symptom score.ConclusionLong-term MMT enhanced the connectivity within the DMN which might be related to reduced withdrawal symptoms, and that between the DMN and SN which might be related to increase in salience values of heroin cues in individuals with HUD. Long-term MMT may be a double-edged sword in treatment for HUD.

It is crucial to synergistically improve the yield and quality of sweet maize by implementing precise and strategic planting methods. However, a comprehensive understanding of how increasing plant density affects the sweet maize fresh ear yield, grain-filling rate, and grain carbohydrate concentration is not fully understood. Thus, a field experiment was performed using a split-plot design in Southeast China in 2021 and 2022, involving four sweet maize varieties (MT6855 and WT2015 were compact-type varieties, XMT10 and YZ7 were flat-type varieties) and three plant densities (D1: 4.5 plants m−2; D2: 6.0 plants m−2; and D3: 7.5 plants m−2). The results showed that an increasing plant density markedly increased the fresh ear yield of sweet maize varieties (MT6855 and WT2015) over the two years. However, it did not influence the fresh ear yield of XMT10 and YZ7. Across all four varieties in 2021 and 2022, the increasing plant density decreased the sweet maize filled ear length, while it did not affect the grain soluble solid concentration and grain residue ratio. The sweet maize grain weight, the maximum grain-filling rate, and the mean grain-filling rate decreased significantly with the increase in planting density across all four varieties. However, plant density did not significantly affect the grain soluble sugar, sucrose, fructose, and starch concentrations across different varieties at most stages during the grain filling. The current study also found that the sweet maize fresh ear yield was dramatically positively correlated with ears ha−1, grains per ear, grain-filling rate, and grain starch concentration but negatively correlated with the bare plant rate. Notably, a parabolic relationship existed between the fresh ear yield and 100-grain weight. These findings suggest that optimizing the plant density, particularly with compact-type varieties, can improve the sweet maize fresh ear yield without decreasing its quality.

Low planting density and lack of density-tolerant varieties are the critical factors limiting the yield of sweet maize in Southeast China. However, there is relatively limited information about the interaction effects of plant density and variety on sweet maize in Southeast China. A two-year (2021–2022) field experiment was conducted with two sweet maize varieties (MT6855 and XMT10) and three plant densities (D1: 45,000 plants ha−1, D2: 60,000 plants ha−1, and D3: 75,000 plants ha−1). The results showed that plant density and variety had significant interaction effects on sweet maize yield and most traits. Increasing plant density significantly increased the fresh ear yield of MT6855, while it did not affect the XMT10 variety. The increase in fresh ear yield for MT6855 under D2 treatment was 14.9% and 14.0% higher than that under D1 treatment in 2021 and 2022, respectively. Meanwhile, increasing plant density significantly increased the bare plant rate and decreased the number of grains per ear of XMT10, while no sustainable changes were observed in MT6855. Moreover, we observed significantly increased pre-silking dry matter, N, P, and K accumulation across different densities in both varieties. In contrast, during the post-silking stage, the increasing plant density significantly improved the accumulation of dry matter, N, P, and K, only in MT6855 but not in XMT10. Meanwhile, harvest index, dry matter remobilization, and leaf N, P, and K remobilization of MT6855 were significantly higher than those of XMT10. Increasing plant density significantly increased N, P, and K partial factor productivity of MT6855 but did not remarkably affect those of XMT10. In addition, fresh ear yield of sweet maize was significantly and positively correlated with pre-silking, post-silking, and total N and P accumulation but had no significant relationship with leaf K remobilization across the two varieties. These results suggest that MT6855 is a density-tolerant variety of sweet maize, and optimizing planting density with a density-tolerant variety can improve the accumulation and remobilization of dry matter and nutrients, thereby improving the fresh ear yield and nutrient use efficiency of sweet maize.

Motivated by the application of high-density data storage technologies, Cassuto and Blaum introduced codes for symbol-pair read channels in 2011, and Yaakobi et al. generalized the coding framework to that for b-symbol read channels where b≥2 in 2016. In this paper, we establish a b-sphere-packing bound and present a recurrence relationship for the b-weight enumerator. We determine all parameters of linear perfect b-symbol e-error-correcting codes over Fq for e<2b and show that for 2b≤e<3b, there exist at most finite such codes for a given b, e, and q. We construct a family of linear perfect b-symbol b-error-correcting codes over Fq using constacyclic codes.

BackgroundHypertension, sleep disorders, and depression are highly prevalent in the elderly population and are all associated with cognitive impairment, but the role that sleep quality and depression play in the association between hypertension and cognitive impairment is unclear. The aim of this study was to investigate whether sleep quality and depression have a mediating role in the association between hypertension and cognitive impairment.MethodsA cross-sectional study was conducted to collect data from the Tongji Hospital Comprehensive Geriatric Assessment Database. Sleep quality, depression and cognitive function were measured by the Pittsburgh Sleep Quality Index (PSQI), the Geriatric Depression Scale (GDS-15) and the Mini-Mental State Examination (MMSE), respectively. Correlation analysis, regression analysis and Bootstrap analysis were used to examine correlations between key variables and mediating effects of sleep quality and depression. Adjustments for multiple comparisons were performed using Benjamini-Hochberg adjustment for multiple testing.ResultsA total of 827 participants were included, hypertension was present in 68.3% of the sample. After correcting for covariates, hypertensive patients aged 65 years or older had worse cognitive function, poorer-sleep quality and higher levels of depression. Sleep quality was significantly negatively associated with depression and cognitive function, while depression was negatively associated with cognitive function. Mediation analysis revealed that hypertension can affect cognitive function in older adults through a single mediating effect of sleep quality and depression and a chain mediating effect of sleep quality and depression.ConclusionThis study found that sleep quality and depression can mediate the relationship between hypertension and cognitive function in elderly. Enhanced supervision of sleep quality and depression in elderly patients with hypertension may be beneficial in maintaining cognitive function.

Drought substantially influences crop growth and development. NAC (NAM, ATAF1/2, and CUC2) transcription factors (TFs) have received much attention for their critical roles in drought stress responses. To explore the maize NAC genes in response to drought stress, the transcriptome sequencing data of NAC TFs in two maize inbred lines, the drought tolerance line H082183 and the sensitive line Lv28, were used to screen the differentially expressed genes (DEGs). There were 129 maize NAC protein-coding genes identified, of which 15 and 20 NAC genes were differentially expressed between the two genotypes under MD and SD treatments, respectively. Meanwhile, the phylogenetic relationship of 152 non-redundant NAC family TFs in maize was generated. The maize NAC family proteins were grouped into 13 distinct subfamilies. Five drought stress–responsive NAC family members, which were designed as ZmNAP, ZmNAC19, ZmNAC4, ZmJUB1(JUBGBRUNNEN1), and ZmNAC87, were selected for further study. The expression of ZmNAP, ZmNAC19, ZmNAC4, ZmJUB1, and ZmNAC87 were significantly induced by drought, dehydration, polyethylene glycol (PEG) stress, and abscisic acid (ABA) treatments. The overexpressing Arabidopsis of these five NAC genes was generated for functional characterization, respectively. Under different concentrations of NaCl, D-mannitol stress, and ABA treatments, the sensitivity of ZmNAP-, ZmNAC19-, ZmNAC4-, ZmJUB1-, and ZmNAC87-overexpressing lines was significantly increased at the germination stage compared to the wild-type lines. The overexpression of these five NAC members significantly improved the drought stress tolerance in transgenic Arabidopsis. Yeast two-hybrid screening analysis revealed that ZmNAP may cooperatively interact with 11 proteins including ZmNAC19 to activate the drought stress response. The above results inferred that ZmNAP, ZmNAC19, ZmNAC4, ZmJUB1, and ZmNAC87 may play important roles in the plant response to drought stress and may be useful in bioengineering breeding and drought tolerance improvement.

Oxidative stress and ferroptosis exhibit crosstalk in many types of human diseases, including malignant tumors. We aimed to develop an oxidative stress- and ferroptosis-related gene (OFRG) prognostic signature to predict the prognosis and therapeutic response in patients with colorectal cancer (CRC). Thirty-four insertion genes between oxidative stress-related genes and ferroptosis-related genes were identified as OFRGs. We then performed bioinformatics analysis of the expression profiles of 34 OFRGs and clinical information of patients obtained from multiple datasets. Patients with CRC were divided into three OFRG clusters, and differentially expressed genes (DEGs) between clusters were identified. OFRG clusters correlated with patient survival and immune cell infiltration. Prognosis-related DEGs in three clusters were used to calculate the risk score, and a prognostic signature was constructed according to the risk score. In this study, patients in the low-risk group had better prognosis, higher immune cell infiltration levels, and better responses to fluorouracil-based chemotherapy and immune checkpoint blockade therapy than high-risk patients; these results were successfully validated with multiple independent datasets. Thus, low-risk CRC could be defined as hot tumors and high-risk CRC could be defined as cold tumors. To further identify potential biomarkers for CRC, the expression levels of five signature genes in CRC and adjacent normal tissues were further verified via an in vitro experiment. In conclusion, we identified 34 OFRGs and constructed an OFRG-related prognostic signature, which showed excellent performance in predicting survival and therapeutic responses for patients with CRC. This could help to distinguish cold and hot tumors in CRC, and the results might be helpful for precise treatment protocols in clinical practice.

BackgroundThe evidence for associations of emotional/behavioral status with sedentary behavior (SB), physical activity (PA) and step counts is scarce in children with autism spectrum disorder (ASD). Also, ASD-related deficiencies may affect actual levels of PA. We aimed to describe accelerometer-measured SB, PA and step counts in children with ASD, and to examine the associations of emotional/behavioral problems with SB, PA and step counts after assessing associations between accelerometer-measured SB, PA and step counts and ASD-related deficiencies.MethodsA total of 93 ASD children, aged 6–9 years, were recruited from the Center for Child and Adolescent Psychology and Behavioral Development of Sun Yat-sen University in Guangzhou, China. Participants wore an accelerometer for seven consecutive days. Of the original 93, 78 participants' accelerometer-measured valid PA were obtained, and the data were shown as time spent in SB, light, moderate, moderate-to-vigorous and vigorous PA, and step counts. Participants' emotional/behavioral problems were assessed via the Strengths and Difficulties Questionnaire (SDQ), and anxiety symptoms were evaluated by the Screen for Child Anxiety Related Emotional Disorders (SCARED). ASD-associated deficiencies include restricted repetitive behaviors (Repetitive Behavior Scale-Revised), poor social competence (Social Responsiveness Scale Second Edition) and motor development restrictions (Developmental Coordination Disorder Questionnaire).ResultsOf the 78 participants, daily vigorous PA (VPA) and moderate-to-vigorous PA (MVPA) averaged 15.62 and 51.95 min, respectively. After adjustment for covariates, SDQ emotional symptoms (β = −0.060, p = 0.028) were inversely associated with the average daily minutes in VPA. Meanwhile, SDQ emotional symptoms (β = −0.033, p = 0.016) were inversely associated with the average daily MVPA minutes in the crude model. After adjustment for covariates, SCARED somatic/panic (β = −0.007, p = 0.040) and generalized anxiety (β = −0.025, p = 0.014) were negatively associated with the average daily VPA minutes; SCARED total anxiety (β = −0.006, p = 0.029) was conversely associated with daily MVPA duration. After adjustment for covariates, no significant associations between accelerometer-measured SB, PA and step counts and ASD-related deficiencies were found (p > 0.05).ConclusionsAccelerometer-measured SB, PA and step counts showed no associations with ASD-related deficiencies. On this basis, we further found that the emotional symptoms were inversely associated with VPA and MVPA. These results emphasize the importance of VPA and MVPA in children with ASD. The longitudinally investigations on the directionality of these associations between emotional symptoms with VPA and MVPA are needed in the future.

Abstract Intense fishing pressure and climate change are major threats to the fish population and coastal fisheries. Larimichthys crocea (large yellow croaker) is a long‐lived fish, which performs seasonal migrations from its spawning and nursery grounds along the coast of the East China Sea (ECS) to overwintering grounds offshore. This study used length‐based analysis and habitat suitability index (HSI) model to evaluate the current life‐history parameters and overwintering habitat suitability of L. crocea, respectively. We compared recent (2019) and historical (1971–1982) life‐history parameters and overwintering HSI to analyze the fishing pressure and climate change effects on the overall population and overwintering phase of L. crocea. The length‐based analysis indicated serious overfishing of L. crocea, characterized by reduced catch, size truncation, constrained distribution, and advanced maturation causing a recruitment bottleneck. The overwintering HSI modeling results indicated that climate change has led to decreased sea surface temperature during L. crocea overwintering phase over the last half‐century, which in turn led to area decrease and an offshore‐oriented shifting of optimal overwintering habitat of L. crocea. The fishing‐caused size truncation may have constrained the migratory ability, and distribution of L. crocea subsequently led to the mismatch of the optimal overwintering habitat against climate change background, namely habitat bottleneck. Hence, while heavy fishing was the major cause of L. crocea collapse, climate‐induced overwintering habitat suitability may have intensified the fishery collapse of L. crocea population. It is important for management to consider both overfishing and climate change issues when developing stock enhancement activities and policy regulations, particularly for migratory long‐lived fish that share a similar life history to L. crocea. Combined with China's current restocking and stock enhancement initiatives, we propose recommendations for the future restocking of L. crocea in China.

Background: Cellular senescence is a typical irreversible form of life stagnation, and recent studies have suggested that long non-coding ribonucleic acids (lncRNA) regulate the occurrence and development of various tumors. In the present study, we attempted to construct a novel signature for predicting the survival of patients with hepatocellular carcinoma (HCC) and the associated immune landscape based on senescence-related (sr) lncRNAs.Method: Expression profiles of srlncRNAs in 424 patients with HCC were retrieved from The Cancer Genome Atlas database. Lasso and Cox regression analyses were performed to identify differentially expressed lncRNAs related to senescence. The prediction efficiency of the signature was checked using a receiver operating characteristic (ROC) curve, Kaplan–Meier analysis, Cox regression analyses, nomogram, and calibration. The risk groups of the gene set enrichment analysis, immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) were also analyzed. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the levels of AC026412.3, AL451069.3, and AL031985.3 in normal hepatic and HCC cell lines.Results: We identified 3 srlncRNAs (AC026412.3, AL451069.3, and AL031985.3) and constructed a new risk model. The results of the ROC curve and Kaplan–Meier analysis suggested that it was concordant with the prediction. Furthermore, a nomogram model was constructed to accurately predict patient prognosis. The risk score also correlated with immune cell infiltration status, immune checkpoint expression, and chemosensitivity. The results of qPCR revealed that AC026412.3 and AL451069.3 were significantly upregulated in hepatoma cell lines.Conclusion: The novel srlncRNA (AC026412.3, AL451069.3, and AL031985.3) signatures may provide insights into new therapies and prognosis predictions for patients with HCC.

The association between sugar-sweetened beverages (SSBs) consumption and executive function (EF) among typically developing (TD) children has been investigated in previous studies but with inconsistent results. Furthermore, this relationship has been less investigated among autistic children who perform worse in EF compared with TD children. In this study, we aimed to investigate the association between SSB consumption and EF in autistic children, and whether the association between SSB and EF in autistic children is different from that in TD children. We recruited 106 autistic children and 207 TD children aged 6–12 years in Guangzhou, China. Children’s EF was assessed by using the Chinese version of parent-reported Behavior Rating Inventory of Executive Function, Stroop Color–Word Test, and working memory subscales of the Chinese version of Wechsler Intelligence Scale for children, Fourth edition. Meanwhile, we assessed children’s dietary intake and SSB consumption with a validated Food Frequency Questionnaire. In this study, 70 (66.0%) autistic children consumed SSB and 20 (18.9%) of them consumed more than two servings SSB a week. Among autistic children, over two servings per week SSB consumption was associated with poorer performance in emotional control [β = 7.20, 95% confidence interval (CI): 0.94–13.46] and plan/Organize (β = 6.45, 95% CI: 0.27–12.63). The association between over two servings/week SSB consumption and emotional control among autistic children was significantly different from that among TD children (βASD = 7.20; βTD = −3.09, Z = 2.72, p = 0.006). Results of this study show that SSB consumption was associated with an impairment in some subscales of EF in autistic children. Furthermore, the association between SSB and EF in autistic children might be different from that in TD children.

BackgroundEmotional and behavioral problems are common in children with autism spectrum disorder (ASD). It's still unclear whether children with ASD have abnormal sugar-sweetened beverages (SSBs) and milk intake and whether this abnormality will affect their emotions and behavior remains unclear. The current study aims to investigate the association of SSBs and milk intake with emotional and behavioral problems in children with autism spectrum disorder (ASD).Methods107 children with ASD and 207 typical developing (TD) children aged 6-12 years old were recruited for the study. The frequency of SSBs and milk intake was assessed by a self-designed questionnaire. Emotional and behavioral problems were assessed by Strength and Difficulties Questionnaire (SDQ). Then, the linear regression model was produced to evaluate the association of SSBs and milk intake with emotional and behavioral problems.ResultsIn the current study, there was no difference in frequency of SSBs intake between children with ASD and TD children (p > 0.05), and children with ASD consumed less milk compared to TD children (p < 0.05). After adjusting sex, age, maternal and paternal education, and monthly family income, we found a significant difference in each subscale score of SDQ in the two groups (p < 0.05). In children with ASD, higher frequent SSBs intake was positively associated with the scores of the emotional problem (p for trend 0.05).ConclusionIn children with ASD, frequency of SSBs and milk intake was associated with the emotional problem and prosocial behavior, respectively. Children with ASD should increase the frequency of milk intake and decrease the frequency of SSBs intake.

Abstract Self-piercing riveting (SPR) has been widely used in automobile industry, and the strength prediction of SPR joints always attracts the attention of researchers. In this work, a prediction method of the cross-tension strength of SPR joints was proposed on the basis of finite element (FE) simulation and extreme gradient boosting decision tree (XGBoost) algorithm. An FE model of SPR process was established to simulate the plastic deformations of rivet and substrate materials and verified in terms of cross-sectional dimensions of SPR joints. The residual mechanical field from SPR process simulation was imported into a 2D FE model for the cross-tension testing simulation of SPR joints, and cross-tension strengths from FE simulation show a good consistence with the experiment result. Based on the verified FE model, the mechanical properties and thickness of substrate materials were varied and then used for FE simulation to obtain cross-tension strengths of a number of SPR joints, which were used to train the regression model based on the XGBoost algorithm in order to achieve prediction for cross-tension strength of SPR joints. Results show that the cross-tension strengths of SPR steel/aluminum joints could be successfully predicted by the XGBoost regression model with a respective error less than 7.6% compared to experimental values.

Background: White matter hyperintensity (WMH) is prevalent in older adults aged 60 and above. A large proportion of people with WMH have not experienced stroke and little has been reported in the literature. Methods: The case data of patients aged ≥60 years without stroke in Wuhan Tongji Hospital from January 2015 to December 2019 were retrospectively analyzed. It was a cross-sectional study. Univariate analysis and logistic regression were used to analyze independent risk factors for WMH. The severity of WMH was assessed using the Fazekas scores. The participants with WMH were divided into periventricular white matter hyperintensity (PWMH) group and deep white matter hyperintensity (DWMH) group, then the risk factors of WMH severity were explored separately. Results: Eventually, 655 patients were included; among the patients, 574 (87.6%) were diagnosed with WMH. Binary logistic regression showed that age and hypertension were associated with the prevalence of WMH. Ordinal logistic regression showed that age, homocysteine, and proteinuria were associated with the severity of WMH. Age and proteinuria were associated with the severity of PWMH. Age and proteinuria were associated with the severity of DWMH. Conclusions: The present study showed that in patients aged ≥60 years without stroke, age and hypertension were independent risk factors for the prevalence of WMH; while the increasing of age, homocysteine, and proteinuria were associated with greater WMH burden.

Background Whether circRAN, which acts as a microRNA sponge, plays a role in 5-fluorouracil (5-Fu) resistant gastric cancer has not been reported. In this study, a 5-Fu resistant cell line with an IC50 of 16.59 µM was constructed. Methods Using comparative analysis of circRNA in the transcriptomics of resistant and sensitive strains, 31 differentially expressed circRNAs were detected, and the microRNA interacting with them was predicted. Results Hsacirc_004413 was selected for verification in drug resistant and sensitive cells. By interfering with hsacirc_004413 using antisense RNA, the sensitivity of drug resistant cells to 5-Fu was significantly promoted, and the apoptosis and necrosis of the cells were significantly increased. In sensitive cells, inhibition by inhibitors enhanced the resistance of cells to 5-Fu. We hypothesize that hsacirc_004413 makes gastric cancer cells resistant to 5-Fu mainly through adsorption of miR-145-5p.

Abstract Aluminum alloys have drawn considerable attention in the area of automotive lightweight. High strength aluminum alloys are usually deformed at elevated temperatures due to their poor formability at room temperature. In this work, the yield behavior of 7075 aluminum alloy in T6 temper (AA7075-T6) within the temperature ranging from 25 °C to 230 °C was investigated. Uniaxial and biaxial tensile tests with the aid of induction heating system were performed to determine the stress vs. strain curves and the yield loci of AA7075-T6 at elevated temperatures, respectively. Von Mises, Hill48 and Yld2000-2d yield criteria were applied to predicting yield loci which were compared with experimentally measured yield loci of the AA7075-T6. Results show that yield stress corresponding to the same equivalent plastic strain decreases with increasing temperature within the investigated temperature range and the shape of yield loci evolves nearly negligibly. The experimental yield locus expands with an increase of equivalent plastic strain at the same temperature and the work hardening rate of AA7075-T6 exhibits obvious stress-state-dependency. The non-quadratic Yld2000-2d yield criterion describes the yield surfaces of AA7075-T6 more accurately than the quadratic von Mises and Hill48 yield criteria, and an exponent of 14 in the Yld2000-2d yield function gives the optimal predictions for the AA7075-T6 at all investigated temperatures.

Abstract Background Chronic active Epstein-Barr virus infection (CAEBV) is a rare disease, which is difficult to be differentiated from inflammatory bowel disease (IBD). To cause the attention, we present twelve cases of CAEBV in immunocompetent patients with gastrointestinal tract involvement. Methods Twelve patients who fulfilled the diagnostic criteria of CAEBV were enrolled in this retrospective study. The control group was consisted of twenty-four IBD patients with EBV-DNA value increased in peripheral blood. The clinicopathologic and endoscopic characteristics were reviewed and analyzed. Results The major clinical presentations of CAEBV patients were intermittent fever (100%), hepatomegaly/splenomegaly (58%), lymphadenopathy (50%), diarrhea (50%) and hematochezia (50%). Compared with IBD patients, the incidence of intermittent fever and increased level of ferritin were significantly higher among CAEBV patients. The median values for EBV detected in peripheral blood were significantly higher in CAEBV group (1.42*10^6 copies/μg) than in IBD group (3.2*10^3 copies/μg, p

Surface plasmon resonance microscopy (SPRM) has been widely employed in biological fields because of its high spatial resolution and label-free detection modality. In this study, SPRM based on total internal reflection (TIR) is studied via a home-built SPRM system, and the principle of imaging of a single nanoparticle is analyzed as well. By designing a ring filter and combining it with the deconvolution algorithm in Fourier space, the parabolic tail of the nanoparticle image is removed, in which a spatial resolution of 248 nm is obtained. In addition, we also measured the specific binding between the human IgG antigen and goat anti-human IgG antibody using the TIR-based SPRM. The experimental results have proved that the system can image sparse nanoparticles and monitor biomolecular interactions.

In nanoplatform-based tumor treatment, combining chemotherapy with hyperthermia therapy is an interesting strategy to achieve enhanced therapeutic efficacy with low dose of delivery drugs. Compared to photothermal therapy, magnetic hyperthermia has few restrictions on penetrating tissue by an alternating magnetic field, and thereby could cure various solid tumors, even deep-tissue ones. In this work, we proposed to construct magnetic nanocomposites (Fe3O4@PDA@ZIF-90) by the external growth of metal-organic framework ZIF-90 on polydopamine (PDA)-coated Fe3O4 nanoparticles for synergistic magnetic hyperthermia and chemotherapy. In such multifunctional platform, Fe3O4 nanoparticle was utilized as a magnetic heating seed, PDA layer acted as an inducer for the growth of ZIF-90 shell and porous ZIF-90 shell served as drug nanocarrier to load doxorubicin (DOX). The well-defined Fe3O4@PDA@ZIF-90 core-shell nanoparticles were displayed with an average size of ca. 200 nm and possessed the abilities to load high capacity of DOX as well as trigger drug release in a pH-responsive way. Furthermore, the Fe3O4@PDA@ZIF-90 nanoparticles can raise the local temperature to meet hyperthermia condition under an alternating magnetic field owing to the magnetocaloric effect of Fe3O4 cores. In the in vitro experiments, the Fe3O4@PDA@ZIF-90 nanoparticles showed a negligible cytotoxicity to Hela cells. More significantly, after cellular internalization, the DOX-loaded Fe3O4@PDA@ZIF-90 nanoparticles exhibited distinctively synergistic effect to kill tumor cells with higher efficacy compared to chemotherapy or magnetic hyperthermia alone, presenting a great potential for efficient tumor therapy.

Intensity interrogation surface plasmon resonance (ISPR) sensing has a simple schematic design and is the most widely used surface plasmon resonance technology at present. However, it has relatively low sensitivity, especially for ISPR imaging (ISPRi). In this paper, a new technique for the real-time monitoring of biomolecule binding on sensor surfaces via ISPRi detection is described. The technique is based on the interrogation of the differential value of two intensities at two specific wavelengths from the reflected light spectrum. In addition, we also optimized the selection of dual-wavelength parameters under different circumstances to achieve the highest sensitivity. The new technique achieved a refractive index resolution (RIR) of 2.24 × 10–6 RIU, which is far beyond that of traditional ISPRi technique. Moreover, our new ISPRi technique also realized the real-time detection of high-throughput biomolecular binding. This study is expected to promote the development of faster and more accurate SPRi technologies.

Abstract Biodegradation is a crucial issue for silica‐based mesoporous nanoparticles that is related to the biosafety in tumor therapy. Nowadays, mesoporous silica nanoparticles (MSNs) have been intensively developed to construct multifunctional nanosystems for tumor therapy due to their biocompatibility, high drug loading capacity and easy functionalization; however, their biodegradation is relatively slow and still under debate. To improve the biodegradability of silica‐based mesoporous nanoparticles, a simple organic‐inorganic hybridization strategy to synthesize mesoporous organosilica nanoparticles (MONs) has been successfully developed. By hybridizing the silica framework (–Si–O–Si–) with stimuli‐sensitive organic moieties to form organic‐inorganic network (–Si–R–Si–, R: organic moiety), when exposed to the stimuli environment, the breakdown of the organic‐inorganic network could accelerate the degradation of MONs, which is great promising for MONs as a multifunctional therapeutic nanoplatform in tumor therapy. This review aims to summarize the degradation strategies for MONs to improve biodegradability in recent years, and highlight the potential applications of MONs in tumor therapy. Finally, we also discuss the challenges of MONs for tumor therapy in future clinical translation.

Accurate house dust mite (HDM) genome and transcriptome data would promote our understanding of HDM allergens. We sought to assemble chromosome-level genome and precise transcriptome profiling of Dermatophagoides farinae and identify novel allergens. In this study, genetic material extracted from HDM bodies and eggs were sequenced. Short-reads from next generation sequencing (NGS) and long-reads from PacBio/Nanopore sequencing were used to construct the D. farinae nuclear genome, transcriptome, and mitochondrial genome. The candidate homologs were screened through aligning our assembled transcriptome data with amino acid sequences in the WHO/IUIS database. Our results showed that compared with the D. farinae draft genome, bacterial DNA content in the presently developed sequencing reads was dramatically reduced (from 22.9888% to 1.5585%), genome size was corrected (from 53.55 Mb to 58.77 Mb), and the contig N50 was increased (from 8.54 kb to 9365.49 kb). The assembled genome has 10 contigs with minimal microbial contamination, 33 canonical allergens and 2 novel allergens. Eight homologs (≥50% homology) were cloned; 2 bound HDM allergic-sera and were identified as allergens (Der f 37 and Der f 39). In conclusion, a chromosome-level genome, transcriptome and mitochondrial genome of D. farinae was generated to support allergen identification and development of diagnostics and immunotherapeutic vaccines.

Structured illumination microscopy (SIM) is an essential super-resolution microscopy technique that enhances resolution. Several images are required to reconstruct a super-resolution image. However, linear SIM resolution enhancement can only increase the spatial resolution of microscopy by a factor of two at most because the frequency of the structured illumination pattern is limited by the cutoff frequency of the excitation point spread function. The frequency of the pattern generated by the nonlinear response in samples is not limited; therefore, nonlinear SIM (NL-SIM), in theory, has no inherent limit to the resolution. In the present study, we describe a two-photon nonlinear SIM (2P-SIM) technique using a multiple harmonics scanning pattern that employs a composite structured illumination pattern, which can produce a higher order harmonic pattern based on the fluorescence nonlinear response in a 2P process. The theoretical models of super-resolution imaging were established through our simulation, which describes the working mechanism of the multi-frequency structure of the nonsinusoidal function to improve the resolution. The simulation results predict that a 5-fold improvement in resolution in the 2P-SIM is possible.

Surface plasmon resonance microscopy (SPRM) is a versatile technique for biosensing and imaging that facilitates high-sensitivity, label-free, real-time characterization. To date, SPR technology has been successfully commercialized and its performance has continued to improve. However, this method is inhibited by low spatial resolution and the inability to achieve single-molecule detection. In this report, we present an overview of SPRM research progress in the field of plasma imaging and sensing. A brief review of the technological advances in SPRM is outlined, as well as research progress in important applications. The combination of various new techniques with SPRM is emphasized. Finally, the current challenges and outlook of this technique are discussed.

The microfluidic-based, label-free image-guided cell sorter offers a low-cost, high information content, and disposable solution that overcomes many limitations in conventional cell sorters. However, flow confinement for most microfluidic devices is generally only one-dimensional using sheath flow. As a result, the equilibrium distribution of cells spreads beyond the focal plane of commonly used Gaussian laser excitation beams, resulting in a large number of blurred images that hinder subsequent cell sorting based on cell image features. To address this issue, we present a Bessel–Gaussian beam image-guided cell sorter with an ultra-long depth of focus, enabling focused images of >85% of passing cells. This system features label-free sorting capabilities based on features extracted from the output temporal waveform of a photomultiplier tube (PMT) detector. For the sorting of polystyrene beads, SKNO1 leukemia cells, and Scenedesmus green algae, our results indicate a sorting purity of 97%, 97%, and 98%, respectively, showing that the temporal waveforms from the PMT outputs have strong correlations with cell image features. These correlations are also confirmed by off-line reconstructed cell images from a temporal–spatial transformation algorithm tailored to the scanning Bessel–Gaussian beam.

The resolution of fluorescence microscopy is limited by the diffraction imaging system, and many methods have been proposed to overcome the optical diffraction limit for achieving super-resolution imaging. Structured illumination microscopy (SIM) is one of the most competitive approaches and has demonstrated remarkable achievements. In the last two decades, SIM has been improved in many aspects, such as the enhancement of resolution and imaging depth and virtual modulation-based SIM. In this Perspective, we present an overview of the development of SIM, including the basic theory, application to biomedical studies, and the remarkable progress of SIM. Owing to its flexibility with respect to combination with other methods, SIM can be considered a powerful tool for biomedical study, offering augmented imaging capabilities by exploiting complementary advantages.

During the luteinization after ovulation in mammalian ovary, the containing cells undergo an energy consuming function re-determination process to differentiate into luteal cells under avascular environment. Previous evidences have delineated the contribution of autophagy to the cell differentiation and the catabolic homeostasis in various types of mammalian cells, whereas few interest had been focused on the involvement of autophagy in the luteinization of granulosa cells during the formation of early corpus luteum. Herein, the present study investigated that expression and contribution of autophagy during granulosa cell luteinization and early luteal development through in vivo and in vitro experiments. The results clearly demonstrated that HIF-1α/BNIP3-mediated autophagy plays a vital role in the luteinization of granulosa cells during the early luteal formation in vivo and in vitro. In the neonatal corpus luteum, HIF-1α up-regulated BNIP3 expressions, which contributed to the autophagic initiation by disrupting beclin1 from Bcl-2/beclin1 complex and protected cells from apoptosis by curbing the skew of mitochondria balance under avascular niche. Notably, Inhibition of HIF-1α activity by echinomycin enhanced the levels of cytoplasmic cytochrome c and cell apoptosis in the nascent corpus luteum. These findings revealed that HIF-1α/BNIP3-mediated autophagy enabled the process of granulosa cell luteinization and protected the granulosa-lutein cells from further apoptosis under hypoxia niche. To our knowledge, the present study firstly clarified that HIF-1α/BNIP3-mediated autophagy contributes to the luteinization of granulosa cells during the formation of pregnant corpus luteum, which will help us further understanding the luteal biology and provide us new clues for the treatment of luteal insufficiency.

Compared with conventional fluorescence biomarker labeling, the classification of cell types based on their stain-free morphological characteristics enables the discovery of a new biological insight and simplifies the traditional cell analysis workflow. Most artificial intelligence aided image-based cell analysis methods primarily use transmitted bright-field images or holographic images. Here, we present the first study of the convolutional neural network (CNN) analysis on three-dimensional (3D) side-scattering cell images out of a unique 3D imaging flow cytometer study. Human cancer cell lines and leukocyte classifications were performed to investigate the information carried by the spatial distribution of side-scattering imaging of single cells. We achieved a balanced accuracy of 98.8% for cancer cell line classification and 92.3% for leukocyte classification. The results demonstrate that the side-scattering signals can not only produce general information about cell granularity following the common belief but also carry rich information about the properties and functions of cells, which can be uncovered by the availability of a side-scattering imaging flow cytometer and the application of CNN. Thereby, we have opened up a new avenue for cell phenotype analysis in biomedical and clinical research.

Transcranial direct current stimulation (tDCS) i a non-invasive brain stimulation which is considered to have the potential to improve cognitive impairment in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, previous studies have been controversial on the therapeutic effect of tDCS. This meta-analysis aimed to evaluate the effects of tDCS on cognitive impairment in patients with MCI and mild-to-moderate AD. Five databases, namely PubMed, EMBASE, MEDLINE, Web of Science and The Cochrane Library, were searched with relative terms to extract the cognitive function changes measured by an objective cognitive scale in the included studies. The meta-analysis results showed that, compared with sham tDCS treatment, the overall cognitive function of patients with AD and MCI was significantly improved (weighted mean difference = 0.99; 95% confidence interval, 0.32 to 1.66; p = 0.004) after tDCS treatment, but the behavioral symptoms, recognition memory function, attention and executive function were not significantly improved. The subgroup analysis showed that the treatment would be more efficacious if the temporal-lobe-related brain areas were stimulated, the number of stimulations was greater than or equal to 10 and the current density was 2.5 mA/cm2. Among them, AD patients benefited more than MCI patients. No cognitive improvement was observed in patients with MCI or AD at different follow-up times after treatment. Our meta-analysis provided important evidence for the cognitive enhancement of tDCS in patients with MCI and mild-to-moderate AD and discussed its underlying mechanisms.

The aero-engine system is complex, and the working environment is harsh. As the fundamental component of the aero-engine control system, the sensor must monitor its health status. Traditional sensor fault detection algorithms often have many parameters, complex architecture, and low detection accuracy. Aiming at this problem, a convolutional neural network (CNN) whose basic unit is an inception block composed of convolution kernels of different sizes in parallel is proposed. The network fully extracts redundant analytical information between sensors through different size convolution kernels and uses it for aero-engine sensor fault detection. On the sensor failure dataset generated by the Monte Carlo simulation method, the detection accuracy of Inception-CNN is 95.41%, which improves the prediction accuracy by 17.27% and 12.69% compared with the best-performing non-neural network algorithm and simple BP neural networks tested in the paper, respectively. In addition, the method simplifies the traditional fault detection unit composed of multiple fusion algorithms into one detection algorithm, which reduces the complexity of the algorithm. Finally, the effectiveness and feasibility of the method are verified in two aspects of the typical sensor fault detection effect and fault detection and isolation process.

Abstract Introduction Methamphetamine has surpassed heroin as the most popular abused drug in China. Although the use of both heroin and methamphetamine leads to use disorders through dysfunction of the dopamine pathway, the incidence of psychiatric disorder caused by methamphetamine abuse is higher than the incidence of psychiatric disorder caused by heroin abuse. The difference in resting‐state function between heroin use disorder (HUD) and methamphetamine use disorder (MAUD) and the relationship between resting‐state function and psychiatric disorder related to MAUD are unknown. Methods In the present study, 21 male individuals with MAUD, 21 demographically matched individuals with HUD, and 21 normal controls (NC) were recruited. The amplitude of low‐frequency fluctuation (ALFF) during resting‐state brain function was measured by magnetic resonance imaging. Psychiatric status was evaluated by the Symptom Checklist‐90 (SCL90). Results Individuals with MAUD had increased SCL90 scores compared to those of the NC for anxiety, paranoia, and additional items, and the hostility score was significantly increased compared to that of individuals with HUD. There is no significant difference between HUD and NC individuals. Individuals with MAUD had increased ALFF compared to those of the NC for thalamus, right postcentral, and right inferior temporal gyri, but a decreased ALFF in the cerebellum. Individuals with HUD had significantly increased ALFF compared to those of the NC for left middle frontal gyrus but a decreased ALFF in the left postcentral gyrus. Individuals with MAUD had significantly increased ALFF compared to those of the HUD for thalamus, the right inferior temporal, and bilateral postcentral gyri, and the ALFF of cerebellum and left middle frontal was significantly increased. Conclusions Methamphetamine can induce more serious psychiatric disorders than heroin. The resting‐state function involved in mood adjustment, the auditory, and memory‐related brain regions may affect psychotic symptoms related to MAUD.

Classification of cell types and isolation of targeted cells according to their imaging and spatial characteristics, beyond traditional fluorescently labeled biomarkers, enable the development of new biological insight and establishment of connections between phenotypical and morphological, and genomic cell information in normal and diseased states. Here, we demonstrate a microfluidic flow cytometer cell sorter that uses fast scanning laser excitation sources and photomultiplier tubes (PMTs), coupled with real-time image processing, to image and sort cells based on user-defined spatial features. Dozens of features, including label-free characteristics such as size, shape, scattering pattern, morphology, as well as the spatial distribution of fluorescently labeled biomarkers, greatly expand the available information space in cell analysis. The use of a disposable microfluidic cartridge that is compatible with the imaging system contributes to size reduction and lowered risk of cross contamination. The so-called cameraless design that uses PMTs to replace CCD makes the system more compatible with conventional fluorescence-activated cell sorters and user friendly, while enjoying the sensitivity and benefits of PMTs. The cell image features can be directly extracted from the temporal waveforms or from the reconstructed cell images via temporal–spatial transformation.