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Root hairs are single-cell projections in the root epidermis. The presence of root hairs greatly expands the root surface, which facilitates soil anchorage and the absorption of water and nutrients. Root hairs are also the ideal system to study the mechanism of polar growth. Previous research has identified many important factors that control different stages of root hair development. Using a chemical genetics screen, in this study we report the identification of a steroid molecule, RHP1, which promotes root hair growth at nanomolar concentrations without obvious change of other developmental processes. We further demonstrate that RHP1 specifically affects tip growth with no significant influence on cell fate or planar polarity. We also show that RHP1 promotes root hair tip growth via acting upstream of the RHD6-RSL4-dependent transcriptional pathway and ROP GTPase-guided local signaling. Finally, we demonstrate that RHP1 exhibits a wide range of effects on different plant species in both monocots and dicots. This study of RHP1 will not only help to dissect the mechanism of root hair tip growth, but also provide a new tool to modify root hair growth in different plant species.

The primary cell wall is a fundamental plant constituent that is flexible but sufficiently rigid to support the plant cell shape. Although many studies have demonstrated that reactive oxygen species (ROS) serve as important signaling messengers to modify the cell wall structure and affect cellular growth, the regulatory mechanism underlying the spatial-temporal regulation of ROS activity for cell wall maintenance remains largely unclear. Here, we demonstrate the role of the Arabidopsis (Arabidopsis thaliana) multicopper oxidase-like protein skewed 5 (SKU5) and its homolog SKU5-similar 1 (SKS1) in root cell wall formation through modulating ROS homeostasis. Loss of SKU5 and SKS1 function resulted in aberrant division planes, protruding cell walls, ectopic deposition of iron, and reduced nicotinamide adeninedinucleotide phosphate (NADPH) oxidase-dependent ROS overproduction in the root epidermis–cortex and cortex–endodermis junctions. A decrease in ROS level or inhibition of NADPH oxidase activity rescued the cell wall defects of sku5 sks1 double mutants. SKU5 and SKS1 proteins were activated by iron treatment, and iron over-accumulated in the walls between the root epidermis and cortex cell layers of sku5 sks1. The glycosylphosphatidylinositol-anchored motif was crucial for membrane association and functionality of SKU5 and SKS1. Overall, our results identified SKU5 and SKS1 as regulators of ROS at the cell surface for regulation of cell wall structure and root cell growth.

Delivery of proteins to the plasma membrane occurs via secretion, which requires tethering, docking, priming, and fusion of vesicles. In yeast and mammalian cells, an evolutionarily conserved RAB GTPase activation cascade functions together with the exocyst and SNARE proteins to coordinate vesicle transport with fusion at the plasma membrane. However, it is unclear whether this is the case in plants. In this study, we show that the small GTPase RABA2a recruits and interacts with the VAMP721/722-SYP121-SNAP33 SNARE ternary complex for membrane fusion. Through immunoprecipitation coupled with mass spectrometry analysis followed by the validatation with a series of biochemical assays, we identified the SNARE proteins VAMP721 and SYP121 as the interactors and downstream effectors of RABA2a. Further expreiments showed that RABA2a interacts with all members of the SNARE complex in its GTP-bound form and modulates the assembly of the VAMP721/722-SYP121-SNAP33 SNARE ternary complex. Intriguingly, we did not observe the interaction of the exocyst subunits with either RABA2a or theSNARE proteins in several different experiments. Neither RABA2a inactivation affects the subcellular localization or assembly of the exocystnor the exocyst subunit mutant exo84b shows the disrupted RABA2a-SNARE association or SNARE assembly, suggesting that the RABA2a-SNARE- and exocyst-mediated secretory pathways are largely independent. Consistently, our live imaging experiments reveal that the two sets of proteins follow non-overlapping trafficking routes, and genetic and cell biologyanalyses indicate that the two pathways select different cargos. Finally, we demonstrate that the plant-specific RABA2a-SNARE pathway is essential for the maintenance of potassium homeostasis in Arabisopsis seedlings. Collectively, our findings imply that higher plants might have generated different endomembrane sorting pathways during evolution and may enable the highly conserved endomembrane proteins to participate in plant-specific trafficking mechanisms for adaptation to the changing environment.

Hongyu Meng,1,2,* Ruixi Li,3,* Yuankang Xie,1,* Zhaohong Mo,2 Hang Zhai,2 Guangquan Zhang,3 Guohui Liang,4 Xianjie Shi,3 Boxuan Zhou1,2 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 4School of Clinical Medicine, Henan University, Kaifeng, People’s Republic of China*These authors contributed equally to this workCorrespondence: Boxuan Zhou; Xianjie Shi, Email zhoubx3@mail2.sysu.edu.cn; shixianjie301@126.cmBackground: Circular RNAs (circRNAs) are becoming vital biomarkers and therapeutic targets for malignant tumors due to their high stability and specificity in tissues. However, biological functions of circRNAs in hepatocellular carcinoma (HCC) are still not well studied.Methods: Gene Expression Omnibus (GEO) database and qRT-PCR were used to evaluate expression of circROBO1 (hsa_circ_0066568) in HCC tissues and cell lines. CCK-8, colony formation, EdU staining, flow cytometry for cell cycle analysis, and xenograft model assays were performed to detect the circROBO1 function in vitro and in vivo. RNA pull-down, RNA immunoprecipitation (RIP), and Luciferase reporter assays were used to investigate the relationship among circROBO1, miR-130a-5p, and CCNT2. More importantly, we developed nanoparticles made from poly lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) chains as the delivery system of si-circROBO1 and then applied them to HCC in vitro and in mice.Results: circROBO1 was obviously upregulated in HCC tissues and cell lines, and elevated circROBO1 was closely correlated with worse prognosis for HCC patients. Functionally, knocking down circROBO1 significantly suppressed HCC cells growth in vitro and in mice. Mechanistically, circROBO1 acted as a competing endogenous RNA to downregulate miR-130a-5p, leading to CCNT2 expression upregulation. Furthermore, miR-130a-5p mimic or CCNT2 knockdown reversed the role of circROBO1 overexpression on HCC cells, which demonstrated that circROBO1 promoted HCC development via miR-130a-5p/CCNT2 axis. In addition, we developed nanoparticles loaded with si-circROBO1, named as PLGA-PEG (si-circROBO1) NPs, which significantly prevented the proliferation of HCC cells, and did not exhibit apparent toxicity to major organs in vivo.Conclusion: Our findings firstly demonstrate that circROBO1 overexpression promotes HCC progression by regulating miR-130a-5p/CCNT2 axis, which may serve as an effective nanotherapeutic target for HCC treatment.Keywords: nanoparticles, hepatocellular carcinoma, circROBO1, cell proliferation, drug delivery

Objective: To evaluate a series of vascular parameters derived from abdominal dual-phase contrast-enhanced CT as predictors of 14-day mortality and AKI within 7 days in septic shock. Methods: 144 patients with septic shock and 60 negative cases were included. The vascular parameters from CT were measured and calculated, including aortic density in arterial (Dena-A) and venous phase (Dena-V), renal vein density in arterial (Denrv-A) and venous phase (Denrv-V), and renal vein-to-aortic density ratio in arterial (DenRrv/a-A) and venous phase (DenRrv/a-V). The parameters were compared between patients and controls, and between patients with different clinical outcomes, and assessed for predictive value of 14-day mortality and AKI within 7 days. Results: Patients with septic shock presented significantly lower Denrv-A (p < 0.001) and DenRrv/a-A (p = 0.002) levels than the controls. In the septic shock group, patients who died had significantly lower Denrv-A (p = 0.001) and lower DenRrv/a-A (p < 0.001) than those who survived. Patients who developed AKI had significantly lower Denrv-A (p < 0.001) and DenRrv/a-A (p = 0.011) than those who did not. Multivariate analysis suggested DenRrv/a-A as an independent predictor of 14-day mortality (OR 0.012; 95% confidence interval [CI]:0.002,0.086; p < 0.001) and Denrv-A as an independent predictor of AKI (OR 0.989;95% CI:0.982,0.997; p = 0.006). Conclusion: In septic shock, significant decreases in Denrv-A and DenRrv/a-A were associated with the onset of AKI and predicted higher 14-day mortality. Advances in knowledge: The renal vein density and renal vein-aortic density ratio in arterial phase of dual-phase contrast-enhanced CT may serve as good predictors of AKI and mortality in septic shock.

Adrenal pheochromocytoma is not always a simple retroperitoneal tumor but may be part of a more complicated condition. It often has a spectrum of complex and variable imaging features, may present as a collision tumor and composite tumor, and is associated with a variety of clinical syndromes. A comprehensive understanding of the clinical, pathological, and variable imaging manifestations of pheochromocytoma can help radiologists make an accurate diagnosis. This article reviews various special imaging features of pheochromocytoma and pheochromocytoma-related diseases.

The North China district has been subjected to significant research with regard to the ore-forming dynamics, processes, and quantitative forecasting of gold deposits; it accounts for the highest number of gold reserves and annual products in China. Based on the top-level design of geoscience theory and the method adopted by the National Key R & D Project (deep process and metallogenic mechanism of North China Craton (NCC) metallogenic system), this paper systematically collects and constructs the geoscience data (district, camp, and deposit scales) in four key gold districts of North China (Jiaojia-Sanshandao, Southern Zhaoping, Wulong, and Qingchengzi). The settings associated with the geological dynamics of gold deposits were quantitatively and synthetically analyzed, namely: NCC destruction, metallogenic events, genetic models, and exploration models. Three-dimensional (3D) and four-dimensional (4D) geological modeling was performed using the big data on the districts, while the district-scale 3D exploration criteria were integrated to construct a quantitative exploration model. Among them, FLAC3D modelling and the GeoCube software (version 3.0) were used to implement the numerical simulation of the 3D geological models and the constraints of the fluid saturation parameters of the Jiaojia fault to reconstruct the 4D fault structure models of the Jiaojia fault (with a depth of 5000 m). Using GeoCube3.0, multiple integration modules (general weights of evidence (WofE), Boost WofE, Fuzzy WofE, Logistic Regression, Information Entropy, and Random Forest) and exploration criteria were integrated, while the C-V fractal classification of A, B and C targets in four districts was carried out. The research results are summarized in the following four areas: (1) Four gold districts in the study area have more than three targets (the depth is 3000 m), and the class A, B and C targets exhibit a good spatial correlation with gold bodies that are controlled by mining engineering at depths greater than 1000 m. (2) The Boost WofE method was used to identify the target optimization in 3D spaces (at depths of 3000–5000 m) of the Jiaojia-Sanshandao, Southern Zhaoping, and Wulong districts. (3) The general WofE method is based on the Bayesian theory in 3D space and provides robust integration and target optimization that are suitable for the Jiaojia-Sanshandao and Southern Zhaoping districts in the Jiaodong area; it can also be applied to the Wulong district in the Liaodong area using a quantitative genetic model and an exploration model. Random forest is a multi-objective integration and target optimization method for 3D spaces, and it is suitable for the complex exploration model in the Qingchengzi district of the Liaodong area. The genetic model and exploration criteria associated with the exploration model of the Qingchengzi district were constrained by the common characteristics of the gold fault structure, magmatic rock emplacement in North China, and the strata fold and interlayer detachment structure. (4) Based on the gold reserves and the 3D block unit model of the Sanshandao gold deposit in the Jiaojia-Sanshandao district, the gold contents of the 3D block units in class A and B targets of the ore concentration were estimated to be 65.5% and 25.1%, respectively. The total Au resources of the optimized targets below a depth of 3000 m were 3908 t (including 1700 t reserves), and the total Au resources of the targets at depths from 3000 to 5000 m were 936 t. The study shows that the deep gold deposits in the four gold districts of North China exhibit a strong “transport-deposition” spatial correlation with potential targets. These “transport-deposition” spatial models represent the tectonic-magmatic-hydrothermal activities of the metallogenic system associated with the NCC destruction events and indicate the Au enrichment zones.

Summary To adapt to the diverse array of biotic and abiotic cues, plants have evolved sophisticated mechanisms to sense changes in environmental conditions and modulate their growth. Growth‐promoting hormones and defence signalling fine tune plant development antagonistically. During host–pathogen interactions, this defence–growth trade‐off is mediated by the counteractive effects of the defence hormone salicylic acid (SA) and the growth hormone auxin.Here we revealed an underlying mechanism of SA regulating auxin signalling by constraining the plasma membrane dynamics of PIN2 auxin efflux transporter in Arabidopsis thaliana roots.The lateral diffusion of PIN2 proteins is constrained by SA signalling, during which PIN2 proteins are condensed into hyperclusters depending on REM1.2‐mediated nanodomain compartmentalisation. Furthermore, membrane nanodomain compartmentalisation by SA or Remorin (REM) assembly significantly suppressed clathrin‐mediated endocytosis. Consequently, SA‐induced heterogeneous surface condensation disrupted asymmetric auxin distribution and the resultant gravitropic response.Our results demonstrated a defence–growth trade‐off mechanism by which SA signalling crosstalked with auxin transport by concentrating membrane‐resident PIN2 into heterogeneous compartments.

Several photosensitizers have recently been proposed as novel approaches against β-lactamase-producing drug-resistant bacteria. However, these reported photosensitizers are rarely used for accurate recognition of drug-resistant bacteria. To tackle this challenge, the structurally modified photosensitizer CySG-2 based on a lipophilic cationic heptamethine indocyanine near-infrared (NIR) dye (IR-780) and an important synthesis intermediate of cephalosporin antibiotic (GCLE) not only achieved the accurate recognition of TEM-1 methicillin-resistant

To investigate the diameter changes of Riolan's arch in patients with isolated superior mesenteric artery dissection (ISMAD) and to evaluate the implication for treatment selection.Ninety-five patients with CT angiography (CTA) confirmed ISMAD were retrospectively included, and another 95 cases with no positive findings on abdominal CTA were included as controls. According to the treatment methods, the patients were subsequently divided into conservative treatment (n = 68) or invasive treatment (n = 27) subgroups. According to the initial CTA images, the prevalence of Riolan's arch as well as its diameter (DRiolan's arch prevalence and DDilation of Riolan's arch is common in patients with ISMAD, and Riolan's arch diameter could be a convenient indicator of disease severity and inform subsequent treatment.

Oxidative stress, cell pyroptosis and inflammation are considered as important pathogenic factors for ulcerative colitis (UC) development, and the traditional anti-alcoholism drug disulfiram (DSF) has recently been reported to exert its regulating effects on all the above cellular functions, which makes DSF as ideal therapeutic agent for UC treatment, but this issue has not been fully studied.Dextran sulfate sodium (DSS)-induced animal models in C57BL/6J mice and lipopolysaccharide (LPS)-induced cellular models in colonic cell lines (HT-29 and Caco-2) for UC were respectively established. Cytokine secretion was determined by ELISA. Cell viability and proliferation were evaluated by MTT assay and EdU assay. Real-Time qPCR, Western Blot, immunofluorescent staining assay and immunohistochemistry (IHC) were employed to evaluate gene expressions. The correlations of the genes in the clinical tissues were analyzed by using the Pearson Correlation analysis.DSF restrained oxidative stress, pyroptotic cell death and cellular inflammation in UC models in vitro and in vivo, and elimination of Reactive Oxygen Species (ROS) by N-acetyl-l-cysteine (NAC) rescued cell viability in LPS-treated colonic cells (HT-29 and Caco-2). Further experiments suggested that a glycogen synthase kinase-3β (GSK-3β)/Nrf2/NLRP3 signaling cascade played critical role in this process. Mechanistically, DSF downregulated GSK-3β and NLRP3, whereas upregulated Nrf2 in LPS-treated colonic cells. Also, the regulating effects of DSF on Nrf2 and NLRP3 were abrogated by upregulating GSK-3β. Moreover, upregulation of GSK-3β abolished the protective effects of DSF on LPS-treated colonic cells.Taken together, data of this study indicated that DSF restrained oxidative damages-related pyroptotic cell death and inflammation via regulating the GSK-3β/Nrf2/NLRP3 pathway, leading to the suppression of LPS-induced UC development.

The homotypic fusion and protein sorting (HOPS) complex is a conserved, multi-subunit tethering complex in eukaryotic cells. In yeast and mammalian cells, the HOPS subunit vacuolar protein sorting-associated protein 41 (VPS41) is recruited to late endosomes after Ras-related protein 7 (Rab7) activation and is essential for vacuole fusion. However, whether VPS41 plays conserved roles in plants is not clear. Here, we demonstrate that in the model plant Arabidopsis (Arabidopsis thaliana), VPS41 localizes to distinct condensates in root cells in addition to its reported localization at the tonoplast. The formation of condensates does not rely on the known upstream regulators but depends on VPS41 self-interaction and is essential for vegetative growth regulation. Genetic evidence indicates that VPS41 is required for both homotypic vacuole fusion and cargo sorting from the adaptor protein complex 3, Rab5, and Golgi-independent pathways but is dispensable for the Rab7 cargo inositol transporter 1. We also show that VPS41 has HOPS-independent functions in vacuolar transport. Taken together, our findings indicate that Arabidopsis VPS41 is a unique subunit of the HOPS complex that carries out plant-specific roles in both vacuolar transport and developmental regulation.

Food supply chains (FSCs) have long been exposed to environmental variability and shock events caused by various economic, political, and infrastructural factors. The outbreak of the COVID-19 pandemic has further exposed and identified the vulnerability of FSCs, and promoted integrated optimization approaches for building resilience. However, existing works focusing on general supply chains (SCs) and FSCs have not been fully aware of the distinct characteristics of FSCs in green logistics, i.e., the expiration of fresh products. In reality, perishable food materials can be processed into products of different processing levels (i.e., multi-level processing) for longer shelf lives, which can serve as a timely and economic strategy to increase safety stocks for mitigating disruption risks. Motivated by this fact, we study the problem of enhancing FSC with a multi-level processing strategy. An integrated location, inventory, and distribution planning model for a multi-echelon FSC under COVID-19-related disruptions is formulated to maximize the total profit over a finite planning horizon. Specifically, a two-stage stochastic programming model is presented to hedge against disruption risks, where scenarios are generated to characterize geographical impact induced by source-region disruptions. For small-scale problems, the model can be solved with commercial solvers. To exactly and efficiently solve the large-scale instances, we design an integer L-shaped method. Numerical experiments are conducted on a case study and randomly generated instances to show the efficiency of our model and solution method. Based on the case study, managerial insights are drawn.

Hydrogen polysulfides (H2Sn, n > 1) belong to sulfane sulfur in the reactive sulfur species (RSS) family and play significant roles in maintaining biological homeostasis in organisms. The detection of H2Sn in living systems is essential, but further understanding of its "intact" function in living cells has been limited, owing to the lack of appropriate analytical tools. In this work, a new fluorescent probe PP-PS was designed for the detection of endogenous H2Sn. The probe has a large Stokes shift (178 nm), low detection limit (1 nM), and short response time (1 minute). Besides, PP-PS was successfully applied in the imaging of endogenous H2Sn in lysosomes of living cancer cells, xenograft mouse tumor tissues, and LPS-induced mouse inflammation tissues. These results revealed that the probe PP-PS could act as a new fluorescence imaging tool to study the function of intracellular hydropolysulfides.

Boron neutron capture therapy (BNCT) has received extensive attention as noninvasive cell-level oncotherapy for treating solid cancer tumors. However, boron-containing drugs such as l-boronophenylalanine (BPA) and sodium borocaptate have low boron content and/or poor tumor-targeting ability, limiting their application. In this study, we designed and synthesized a series of nontoxic, dual-target boron carriers (B139, B142, and B151) with the ability to accumulate specifically in tumor cells. We found that the B139 uptake into hypoxic tumor regions was high, with a 70-fold boron content compared to BPA. In addition, in vivo observation showed that B139 can be trapped in tumor cells for a prolonged period and maintains an effective therapeutic concentration, with a peak boron concentration of 50.7 μg/g and a high tumor: blood boron ratio of >3, achieving ideal BNCT conditions. Cytotoxicity evaluation in mice further proved that B139 is safe and reliable. Therefore, B139 has great potential for BNCT application as a dual-target, safe, and efficient boron carrier.

Conventional chemotherapeutic drugs cause systemic side effects due to nonspecific interactions with healthy tissues, which significantly hinders their tolerability and efficacy. Herein, we develop...

Background Hepatocellular carcinoma (HCC) is frequently associated with metabolism dysfunction. Increasing evidence has demonstrated the crucial role of lipid metabolism in HCC progression. The function of apolipoprotein F (ApoF), a lipid transfer inhibitor protein, in HCC is incompletely understood. We aimed to evaluate the functional role of ApoF in HCC in this study. Methods We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to detect ApoF mRNA expression in HCC tissues and hepatoma cell lines (SMMC-7721, HepG2, and Huh7). Immunohistochemistry was performed to detect the expression of ApoF in HCC tissues. The associations between ApoF expression and clinicopathological features as well as HCC prognosis were analyzed. The effect of ApoF on cellular proliferation and growth of SMMC-7721 and Huh7 cells was examined in vitro and in vivo. Results ApoF expression was significantly down-regulated at both mRNA and protein levels in HCC tissues as compared with adjacent tissues. In SMMC-7721 and Huh7 HCC cells, ApoF overexpression inhibited cell proliferation and migration. In a xenograft nude mouse model, ApoF overexpression effectively controlled HCC growth. Kaplan–Meier analysis results showed that the recurrence-free survival rate of HCC patients with low ApoF expression was significantly lower than that of other HCC patients. Low ApoF expression was associated with several clinicopathological features such as liver cirrhosis, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage. Conclusions ApoF expression was down-regulated in HCC, which was associated with low recurrence-free survival rate. ApoF may serve as a tumor suppressor in HCC and be a potential application for the treatment of this disease.

Background. Cancer of unknown primary (CUP) is a type of malignant tumor, which is histologically diagnosed as a metastatic carcinoma while the tissue-of-origin cannot be identified. CUP accounts for roughly 5% of all cancers. Traditional treatment for CUP is primarily broad-spectrum chemotherapy; however, the prognosis is relatively poor. Thus, it is of clinical importance to accurately infer the tissue-of-origin of CUP. Methods. We developed a gradient boosting framework to trace tissue-of-origin of 20 types of solid tumors. Specifically, we downloaded the expression profiles of 20,501 genes for 7713 samples from The Cancer Genome Atlas (TCGA), which were used as the training data set. The RNA-seq data of 79 tumor samples from 6 cancer types with known origins were also downloaded from the Gene Expression Omnibus (GEO) for an independent data set. Results. 400 genes were selected to train a gradient boosting model for identification of the primary site of the tumor. The overall 10-fold cross-validation accuracy of our method was 96.1% across 20 types of cancer, while the accuracy for the independent data set reached 83.5%. Conclusion. Our gradient boosting framework was proven to be accurate in identifying tumor tissue-of-origin on both training data and independent testing data, which might be of practical usage.

Arginine vasopressin (AVP) neurons in the hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) are involved in important physiological behaviors, such as controling osmotic stability and thermoregulation. However, the presynaptic input patterns governing AVP neurons have remained poorly understood due to their heterogeneity, as well as intermingling of AVP neurons with other neurons both in the SON and PVN. In the present study, we employed a retrograde modified rabies-virus system to reveal the brain areas that provide specific inputs to AVP neurons in the SON and PVN. We found that AVP neurons of the SON and PVN received similar input patterns from multiple areas of the brain, particularly massive afferent inputs from the diencephalon and other brain regions of the limbic system; however, PVNAVP neurons received relatively broader and denser inputs compared to SONAVP neurons. Additionally, SONAVP neurons received more projections from the median preoptic nucleus and organum vasculosum of the lamina terminalis (a circumventricular organ), compared to PVNAVP neurons, while PVNAVP neurons received more afferent inputs from the bed nucleus of stria terminalis and dorsomedial nucleus of the hypothalamus, both of which are thermoregulatory nuclei, compared to those of SONAVP neurons. In addition, both SONAVP and PVNAVP neurons received direct afferent projections from the bilateral suprachiasmatic nucleus, which is the master regulator of circadian rhythms and is concomitantly responsible for fluctuations in AVP levels. Taken together, our present results provide a comprehensive understanding of the specific afferent framework of AVP neurons both in the SON and PVN, and lay the foundation for further dissecting the diverse roles of SONAVP and PVNAVP neurons.

Biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) play important roles in various physiological and pathological processes, and due to their similar structures and reaction activities, it is still challenging to simultaneously discriminate between GSH and Cys/Hcy in vivo. Hence, a novel fluorescent probe for simultaneously discriminating GSH and Cys/Hcy in biological samples is highly desirable. Herein, we presented two enhanced fluorescent probes (Cy1 and Cy2) with doubly-activated dual emission for sensitive and discriminative detection of Cys/Hcy and GSH. The probes were constructed with IR-780 and NBD linked via an ether bond, which responds to GSH with near infrared (NIR) emission at 810 nm (λex = 720 nm) and Cys/Hcy with visible green emission at 550 nm (λex = 470 nm). The probe Cy2 is operable in human serum samples, thus holding promise for its diagnosis-related application. Notably, the results of fluorescence microscopy imaging indicated that Cy2 is suitable for visualization of exogenous and endogenous biothiols in living cells. Furthermore, desirable results were obtained when the probe Cy2 was applied for bioimaging in tumor-bearing mice and acute liver injury (ALI) mice models, which revealed encouraging clinical values of this probe.

In recent years, with the continuous expansion of the enrollment scale of college students in China, the base of university undergraduates has increased significantly, and social competition has become increasingly fierce. Therefore, postgraduate entrance examinations have become one of the important choices for contemporary college students. However, the number of applications for postgraduate entrance examinations in 2020 has reached 3.41 million. It is also an important choice for people to apply for postgraduate entrance examination training courses. Based on the research and understanding of the postgraduate entrance examination market, this article has formulated and implemented a market survey on postgraduate entrance examinations, understood the needs and requirements of college students for postgraduate entrance examinations, and used SPSS Modeler software to conduct correlation analysis on the market survey questionnaires for postgraduate entrance examinations. We get the basic information and suggestions for postgraduate entrance examination institutions.