Structural basis of assembly and torque transmission of the bacterial flagellar motor.

The bacterial flagellar motor is a supramolecular protein machine that drives rotation of the flagellum for motility, which is essential for bacterial survival in different environments and a key determinant of pathogenicity. The detailed structure of the flagellar motor remains unknown. Here we present an atomic-resolution cryoelectron microscopy (cryo-EM) structure of the bacterial flagellar motor complexed with the hook, consisting of 175 subunits with a molecular mass of approximately 6.3 MDa. The structure reveals that 10 peptides protruding from the MS ring with the FlgB and FliE subunits mediate torque transmission from the MS ring to the rod and overcome the symmetry mismatch between the rotational and helical structures in the motor. The LP ring contacts the distal rod and applies electrostatic forces to support its rotation and torque transmission to the hook. This work provides detailed molecular insights into the structure, assembly, and torque transmission mechanisms of the flagellar motor.

An Immunosensor Using Electroactive COF as Signal Probe for Electrochemical Detection of Carcinoembryonic Antigen.

Two kinds of two-dimensional (2D) covalent-organic frameworks (COF) were used to construct a sandwich-type electrochemical immunosensor for a proof-of-concept study. Vinyl-functionalized COFTab-Dva could be linked with Ab1 by the thiol-ene "click" reaction. Electroactive COFTFPB-Thi was modified with gold nanoparticles (AuNPs) to ensure the successful connection with Ab2 through Au-S bond. Meanwhile, electroactive COFTFPB-Thi was used to as signal probe to realize both the detection of carcinoembryonic antigen (CEA) and the amplification of detection signal. In detection process of the sandwich-type electrochemical immunosensor, glassy carbon electrode (GCE) was modified with 2D COFTab-Dva first then connected with Ab1 by the thiol-ene "click" reaction, next quantitative CEA was captured, followed by specificially capturing signal probe of Ab2/AuNPs/COFTFPB-Thi where AuNPs acted as nanocarriers of Ab2 and COFTFPB-Thi served as the signal producers. As the amount of CEA was increased, the amount of signal probe captured to the electrode was also increased, and the peak signal intensity of the redox reaction of COFTFPB-Thi was enhanced accordingly. Thus, the quantitative detection of CEA could be realized according to the peak signal intensity of electroactive COFTFPB-Thi. The electrochemical immunosensor owned wide detection range of 0.11 ng/mL-80 ng/mL, low detection limit of 0.034 ng/mL and good practicability. This study opens up a new revelation for quantitative detection of CEA using electroactive COF as enhanced signal probe.

Mutual interplay between ArcA and σE orchestrates envelope stress response in Shewanella oneidensis.

To survive and thrive in harsh and ever-changing environments, intricate mechanisms have evolved for bacterial cells to monitor perturbations impacting the integrity of their envelope and to mount an appropriate response to contain or repair the damage. In this study, we report in Shewanella oneidensis a previously undescribed mechanism for the envelope defect resulting from the loss of Arc, a two-component transcriptional regulatory system crucial for respiration. We uncovered σE , a master regulator establishing and maintaining the integrity of the cell envelope in γ-proteobacteria, as the determining factor for the cell envelope defect of the arcA mutant. When ArcA is depleted, σE activity is compromised by enhanced production of anti-σE protein RseA. Surprisingly, S. oneidensis σE is not essential for viability, but becomes so in the absence of ArcA. Furthermore, we demonstrated that there is an interplay between these two regulators as arcA expression is affected by availability of σE . Overall, our results underscore functional interplay of regulatory systems for envelope stress response: although each of the systems may respond to perturbation of particular components of the envelope, they are functionally intertwined, working together to form an interconnected safety net.

[Research progress of correlation between multidrug resistance and transporters and traditional Chinese medicine intervention].

With the emergence of drug resistance in Western medicine, the repeated administration of clinical first-line drugs becomes more severe. There are many factors leading to multidrug resistance(MDR), so it is very difficult to solve the problem. Since traditional Chinese medicine(TCM) has been used in the field of MDR in recent years, the research on the transporter-associated drug resistance and intervention of TCM has gradually become a hot spot. Therefore, in order to further explore the relationships among drug resistance, transporters, and TCM intervention, we review the relevant research progress in recent years and comb the achievements and limitations of this research at present. In the end, we put forward the research direction of changing body's ADME through the host's transporters and gastrointestinal flora, which provides new ideas for future research.

Promiscuous Enzymes Cause Biosynthesis of Diverse Siderophores in Shewanella oneidensis.

The siderophore synthetic system in Shewanella species is able to synthesize dozens of macrocyclic siderophores in vitro with synthetic precursors. In vivo, however, although three siderophores are produced naturally in Shewanella algae B516, which carries a lysine decarboxylase (AvbA) specific for siderophore synthesis, only one siderophore can be detected from many other Shewanella species. In this study, we examined a siderophore-overproducing mutant of Shewanella oneidensis which lacks an AvbA counterpart, and we found that it can also produce these three siderophores. We identified both SpeC and SpeF as promiscuous decarboxylases for both lysine and ornithine to synthesize the siderophore precursors cadaverine and putrescine, respectively. Intriguingly, putrescine is mainly synthesized from arginine through an arginine decarboxylation pathway in a constitutive manner, not liable to the concentrations of iron and siderophores. Our results provide further evidence that the substrate availability plays a determining role in siderophore production. Furthermore, we provide evidence to suggest that under iron starvation conditions, cells allocate more putrescine for siderophore biosynthesis by downregulating the expression of the enzyme that transforms putrescine into spermidine. Overall, this study provides another example of the great flexibility of bacterial metabolism that is honed by evolution to better fit living environments of these bacteria.IMPORTANCE The simultaneous production of multiple siderophores is considered a general strategy for microorganisms to rapidly adapt to their ever-changing environments. In this study, we show that some Shewanella spp. may downscale their capability for siderophore synthesis to facilitate adaptation. Although S. oneidensis lacks an enzyme specifically synthesizing cadaverine, it can produce it by using promiscuous ornithine decarboxylases. Despite this ability, this bacterium predominately produces the primary siderophore while restraining the production of secondary siderophores by regulating substrate availability. In addition to using the arginine decarboxylase (ADC) pathway for putrescine synthesis, cells optimize the putrescine pool for siderophore production. Our work provides an insight into the coordinated synthesis of multiple siderophores by harnessing promiscuous enzymes in bacteria and underscores the importance of substrate pools for the biosynthesis of natural products.

[Comparative analysis of active components and transcriptome between autotetraploid and diploid of Dendrobium huoshanense].

In this study, the roots, stems and leaves of diploid and autotetraploid Dendrobium huoshanense were used as materials to compare their contents of polysaccharides and alkaloids, and the transcriptome sequencing analysis was carried out. The results showed that the contents of polysaccharides and alkaloids in the roots, stems and leaves of tetraploid were 7.6%, 34.5%, 17.2%, 0.01%, 0.024% and 0.035% higher than those of diploid D. huoshanense, respectively. The contents of active components in different tissues were significantly different. There were 3 687 differentially expressed genes in diploid and tetraploid D. huoshanense, of which 2 346 genes were up-regulated and 1 341 down regulated. Go functional analysis showed that these genes were mainly involved in growth and development, stress resistance and other related functions. KEGG pathway analysis showed that most of the differential genes were concentrated in the processes of carbon metabolism, signal transduction, carbohydrate metabolism, amino acid metabolism and energy metabolism. The differential expression of key genes involved in the metabolism of polysaccharides, terpenes and polyketones, amino acid metabolism, hormone synthesis and signal transduction in diploid and tetraploid plants may be the main reason for the high energy content, the increase of active components and the growth potential of tetraploid plants.

[Identification and differential expression of miRNA related to seed dormancy of Paris polyphylla var. chinensis].

The purpose of this study was to explore the expression pattern of miRNA in the process of embryo dormancy and provide a reference for the mechanism of regulating seed dormancy and germination by miRNA. We used high-throughput sequencing technology, bioinformatics analysis and real-time fluorescent quantitative PCR(qPCR) technology to sequence, screen and identify miRNAs of dormant and dormant embryos. The results showed that there were 23 811 977, 24 276 695, 20 611 876 and 20 601 811 unique sequences in the four sample libraries during the period of dormancy and dormancy release. MiRNAs are mainly distributed between 21 and 24 nt, among which the length of 24 nt occurred most frequently. A total of 31 known miRNAs were identified, belonging to 13 different families. 93 new miRNAs were predicted by bioinformatics software. Ten miRNAs(mir156 a-5 p, mir160 a-5 p, mir160 h-1, mir169 a-5 p, mir157 d, mir159 a-1, mir395-3, mir156 f-5 p, mir156-2 and mir171 a-3 p) were screened out. In this study, 10 miRNAs related to seed dormancy release were identified. The target genes mainly involved carbohydrate metabolism, plant hormone signal transduction, cell division and growth. The results of qRT-PCR showed that the sequencing results were consistent with the actual results.

[Characterization of AOX family members from Aquilaria sinensis and their responses to wounding].

Aquilaria sinensis is a typical inducible medicinal plant, that can produce agarwood only after it is wounded by external stimuli. Alternative oxidase(AOX) is one of the terminal oxidases of the plant mitochondrial electron transport, which plays an important role in plants' response to environmental stress. In order to reveal the physiological function of AOX gene in the process of agarwood formation from A.sinensis induced by wounding, AOX gene was cloned based on the transcriptome database and then identified by the bioinformatics analysis, and their expression pattern in different tissues and under wounding stress were detected by qRT-PCR. The results as follows. Three AOX genes were cloned from A.sinensis for the first time. They were named AsAOX1a, AsAOX1d and AsAOX2, respectively. The tissue expression shown that AsAOX1a is mainly expressed in the stem and the seed, and the AsAOX1d and AsAOX2 genes are mainly expressed in the pulp and the stem. AsAOX1a and AsAOX1d genes are highly responsive to wounding stress, and their response time was different. In addition, the expression of AsAOX1a and AsAOX2 induced by wounding are reduced by H_2O_2 treatment, but promoted by AsA treatment. The cloning, bioinformatics analysis and expression characteristics of AOX genes from A.sinensis provided basic information for further study the function of AOX genes in the development of A.sinensis, especially in the process of agarwood formation of A. sinensis induced by wounding.

The effect of GNAQ methylation on GnRH secretion in sheep hypothalamic neurons.

Kazakh sheep are seasonal estrous animals, and gonadotropin-releasing hormone (GnRH) is the key to fertility regulation. The nutritional level has a certain regulatory effect on estrous, and vitamin B folate plays a role in DNA methylation, directly participating in the process. The goal of this study was to determine whether folate is involved in GnAQ methylation and its effect on GnRH secretion. The hypothalamic neurons of Kazakh fetal sheep were treated with folate at concentrations of 0 mg/mL, 4 mg/mL, 40 mg/mL, and 80 mg/mL. GnAQ promoter methylation, DNMT1, GnAQ expression, and GnRH secretion following treatment with different concentrations of folate were analyzed. One CpG site was methylated in the GNAQ promoter with 40 mg/mL folic acid, and no CpG methylation was found in the other groups. GnAQ expression was related to folate concentration and showed a trend of increasing first and then decreasing. The GnRH expression level in the 40 mg/mL folate group was significantly higher than in the other three groups ( P < .05). These results demonstrate that the appropriate folate concentration promoted GANQ promoter methylation, which in turn affected GnRH secretion.

Neuro-stimulating effect of Citri Reticulata Pericarpium Viride essential oil through regulating Glu/NMDAR on olfactory bulb to improve anxiety-like behavior.

ETHNOPHARMACOLOGICAL RELEVANCE: Citri Reticulata Pericarpium Viride (also known Qing-Pi or QP) is a plant in the Rutaceae family, QP is a traditional Qi-regulating medicine in Chinese medicine that is compatible with other Chinese medicine components and has extensive clinical practice in treating anxiety and depression. Reports on the pharmacological effects of QP have demonstrated its neuroprotective effects and antioxidant capacities. Numerous pharmacological benefits of QP are attributed to its antioxidant abilities. Anxiety disorders are a broadly defined category of mental illnesses. Oxidative stress and an imbalance in the antioxidant defense system are typical pathological features of these disorders. AIM OF THE STUDY: The aim of this study was to evaluate the effects of QP essential oil on anxiety using animal models and investigate the underlying neurobiological mechanisms. MATERIALS AND METHODS: This study aimed to develop an animal model of anxiety using chronic restraint stress and investigate the effects of inhalation of Citri Reticulata Pericarpium Viride essential oil on anxiety-like behavior, olfactory function, and olfactory bulb neurogenesis in mice with anxiety. RESULTS: The results showed that long-term chronic restraint stimulation caused a decrease in olfactory function, significant anxiety-like behavior, and a notable reduction in the number of neurons in the olfactory bulb. However, inhalation of Citri Reticulata Pericarpium Viride essential oil reversed these effects, improving the olfactory function, neuro-stimulating effect, alleviating anxiety-like behavior, and regulating theta (4-12Hz) oscillation in the hippocampus DG area. These effects were associated with changes in the expression levels of glutamate receptor NMDAR and NeuN in olfactory bulb. CONCLUSIONS: The study revealed that mice with anxiety induced by chronic restraint stress exhibited significant olfactory dysfunction, providing strong evidence for the causal relationship between anxiety disorders and olfactory dysfunction. Moreover, QP essential oil has the potential to be developed as a therapeutic drug for anxiety disorders, in addition to its role as a complementary anxiolytic.

Harnessing Dual Phototherapy and Immune Activation for Cancer Treatment: The Development and Application of BODIPY@F127 Nanoparticles.

Conventional phototherapeutic agents are typically used in either photodynamic therapy (PDT) or photothermal therapy (PTT). However, efficacy is often hindered by hypoxia and elevated levels of heat shock proteins in the tumor microenvironment (TME). To address these limitations, a formylated, near-infrared (NIR)-absorbing and heavy-atom-free Aza-BODIPY dye is presented that exhibits both type-I and type-II PDT actions with a high yield of reactive oxygen species (ROS) and manifests efficient photothermal conversion by precise adjustments to the conjugate structure and electron distribution, leading to a large amount of ROS production even under severe hypoxia. To improve biosafety and water solubility, the dye with an amphiphilic triblock copolymer (Pluronic F-127), yielding BDP-6@F127 nanoparticles (NPs) is coated. Furthermore, inspired by the fact that phototherapy triggers the release of tumor-associated antigens, a strategy that leverages potential immune activation by combining PDT/PTT with immune checkpoint blockade (ICB) therapy to amplify the systemic immune response and achieve the much-desired abscopal effect is developed. In conclusion, this study presents a promising molecular design strategy that integrates multimodal therapeutics for a precise and effective approach to cancer therapy.

A platform for whole-genome speed introgression from Aegilops tauschii to wheat for breeding future crops.

Breeding new and sustainable crop cultivars of high yields and desirable traits has been a major challenge for ensuring food security for the growing global human population. For polyploid crops such as wheat, introducing genetic variation from wild relatives of its subgenomes is a key strategy to improve the quality of their breeding pools. Over the past decades, considerable progress has been made in speed breeding, genome sequencing, high-throughput phenotyping and genomics-assisted breeding, which now allows us to realize whole-genome introgression from wild relatives to modern crops. Here, we present a standardized protocol to rapidly introgress the entire genome of Aegilops tauschii, the progenitor of the D subgenome of bread wheat, into elite wheat backgrounds. This protocol integrates multiple modern high-throughput technologies and includes three major phases: development of synthetic octaploid wheat, generation of hexaploid A. tauschii-wheat introgression lines (A-WIs) and homozygosis of the generated A-WIs. Our approach readily generates stable introgression lines in 2 y, thus greatly accelerating the generation of A-WIs and the introduction of desirable genes from A. tauschii to wheat cultivars. These A-WIs are valuable for wheat-breeding programs and functional gene discovery. The current protocol can be easily modified and used for introgressing the genomes of wild relatives to other polyploid crops.

Fabrication of 3D HierarchicalSphericalHoneycomb-Like Nd2O3/Co3O4/Graphene/Nickel Foam Composite Electrode Material for High-Performance Supercapacitors.

A 3D hierarchical spherical honeycomb-like composite electrode materialof neodymium oxide (Nd2O3), cobalt tetraoxide (Co3O4), and reduced graphene oxide (rGO) on nickel foam (named as Nd2O3/Co3O4/rGO/NF) were successfully fabricated by combining the hydrothermal synthesis method and the annealing process. Nickel foam with a three-dimensional spatial structure was used as the growth substrate without the use of any adhesives. The Nd2O3/Co3O4/rGO/NF composite has outstanding electrochemical performance and can be used directly as an electrode material for supercapacitors (SCs). By taking advantage of the large specific surface area of the electrode material, it effectively slows down the volume expansion of the active material caused by repeated charging and discharging processes, improves the electrode performance in terms of electrical conductivity, and significantly shortens the electron and ion transport paths. At a 1 A/g current density, the specific capacitance reaches a maximum value of 3359.6 F/g. A specific capacitance of 440.4 F/g with a current density of 0.5A/g is still possible from the built symmetric SCs. The capacitance retention rate is still 95.7% after 30,000 cycles of testing at a high current density of 10 A/g, and the energy density is 88.1 Wh/kg at a power density of 300 W/kg. The outcomes of the experiment demonstrate the significant potential and opportunity for this composite material to be used as an electrode material for SCs.

Immunosensing of neuron-specific enolase based on signal amplification strategies via catalysis of ascorbic acid by heteropolysate COF.

In view of the importance of quantification of neuron-specific enolase (NSE), an electrochemical NSE immunosensor was developed. The sandwich voltammetric immunosensor utilized vinyl-functionalized crystalline covalent organic framework (COFTAPT-Dva) modified electrode to load lots of Ab1 via thiol-ene "click" reaction as matrix. A crystalline cationic EB-COF:Br was used to load Au nanoparticles (AuNPs) and H3[PMo12O40] (PMo12) as immunoprobe. The AuNPs with the size of about 30 nm were firstly grown on EB-COF:Br and then a large number of electroactive PMo12 were uniformly assembled on AuNPs/EB-COF:Br via ion exchanging reaction. The AuNPs not only facilitated the bonding of Ab2 based on Au-S bond, but also improved performance of Ab2/AuNPs/EB-COF:PMo12 immunoprobe. The sensitivity of sandwich electrochemical immunosensor could be primarily amplified based on loaded abundant PMo12. Secondary sensitivity amplification of immunosensor could be achieved by using PMo12 to catalyze ascorbic acid. The linear range of sandwich voltammetric immunosensor based on current change of differential pulse voltammetry is 500 ± 36 fg mL-1 - 100 ± 8 ng mL-1. Thanks to the dual sensitivity amplification strategy, the sensitivity is as high as 54.06 ± 3.2 µA cm-2/lg(cNSE/ng mL-1), and the detection limit is as low as 166 ± 10.8 fg mL-1. It proves that it is completely feasible to amplify sensitivity of sandwich voltammetric immunosensors using polyoxometalate-COF and its catalytic substrate.

Reversible splenial lesion syndrome type II in youth mimicking acute ischemic stroke like onset: A case report.

BACKGROUND: Reversible splenial lesion syndrome (RESLES) is a newly recognized syndrome. Its typical pathologic findings is a reversible progress correlated with transiently reduced diffusion lesion in the splenium of the corpus callosum. The common clinical symptoms include mildly altered states consciousness, delirium, and seizure. METHODS: We presented a 21-year-old patient with signs of acute ischemic stroke (AIS), including symptoms of weakness on the right upper limb and aphasia, lasting 50 minutes until he was taken to the emergency. He just had a cough 20 days ago. RESULTS: An elevated level of white blood cell count, neutrophil count, monocyte count, protein of cerebrospinal fluid was found in laboratory examinations. Magnetic resonance imaging revealed distinct lesions involving white matter in the splenium of the corpus callosum and frontal-parietal cortex on both cerebral hemispheres. Digital subtraction angiography examination was also unremarkable. The patient recovered to baseline within 4 days. We treated the patient with glucocorticoid, antiviral drugs, butylphthalide, and dehydrating drugs. In addition, the follow-up brain magnetic resonance imaging scan showed reduced lesions. AIS-like symptoms did not occur during a 30-day follow-up period. CONCLUSION: This patient with reversible splenial lesion syndrome type II exhibited AIS-like symptoms, which was uncommon on clinical. This case extends the recognized clinical phenotypes for this disorder.

Investigating the Mechanical Properties and Durability of Metakaolin-Incorporated Mortar by Different Curing Methods.

In this paper, the traditional, silicate-based Portland cement (PC) was employed as the control to explore the impact of adding varying amounts of metakaolin (MK) on the mechanical properties of cement mortar. In fact, as a mineral admixture, metakaolin (MK) has the ability to significantly improve the early strength and sulfate resistance of cement mortar in traditional, silicate-based Portland cement (PC). In addition to this, the performance of Portland cement mortar is greatly affected by the curing mode. The previous research mainly stays in the intermittent curing and alkaline excitation mode, and there are few studies on the influence of relatively humidity on it. Moreover, the paper investigated the impact of four different curing methods about humidity on the mechanical properties and sulfate resistance. The results show that the best content of metakaolin in Portland cement is 10% (M10), and the best curing method is 95% humidity in the first three days followed by 60% humidity in the later period (3#). Based on previous literature that suggests that adding MK thickens water film layer on the surface of mortar, the mechanism of MK increasing the early strength of cement was analyzed. The compressive strength of the Portland cement containing 10% MK (M10) after 1 day curing is 3.18 times that of pristine PC mortar, and is comparable if PC is cured for three days under the same curing conditions. The traditional PC mortar is highly dependent on the wet curing time, and normally requires a curing time of at least seven days. However, the incorporation of MK can greatly reduce the sensitivity of Portland cement to water; MK cement mortar with only three days wet curing (3#M10) can reach 49.12 MPa after 28 days, which can greatly shorten the otherwise lengthy wet curing time. Lastly, the cement specimens with MK also demonstrated excellent resistance against sulfate corrosion. The work will provide a strong theoretical basis for the early demolding of cement products in construction projects. At the same time, this study can also provide a theoretical reference for the construction of climate drought and saline land areas, which has great reference value.

Effect of Fly Ash and Metakaolin on Properties and Microstructure of Magnesium Oxysulfate Cement.

To improve the mechanical performance and lower the production cost of magnesium oxysulfate cement (MOSC), this article investigates the effects of single and compounded addition of metakaolin (MK) and/or fly ash (FA) on the setting time, mechanical strength, water resistance, hydration product, composition, and microstructure of the resulting cement. MOSC samples with different proportions, ranging from 0 to 30 wt.%, of FA and/or MK substituting magnesium oxide (MgO) were prepared. The microstructure was explored by scanning electron microscopy, X-ray diffraction, and mercury intrusion porosimetry. The findings suggest that adding FA can delay the setting of MOSC; however, the effect of adding MK to MOSC was reversed. Furthermore, the phase composition of the MOSC hydration products was unaltered upon adding FA and/or MK, but thicker and longer 517 phase crystals were observed. FA and MK can effectively fill the large pores of MOSC through filling and nucleation effects, reduce the pore size, and form a denser microstructure, thereby improving its mechanical properties. The optimal MOSC sample was found by substituting 10 wt.% of both FA and MK, resulting in a cement that exhibited a short setting time and an incredibly high mechanical strength and density. These findings will further the development of stronger, more cost-efficient, and more water-resistant MOSC products.

Targeting GNAQ in hypothalamic nerve cells to regulate seasonal estrus in sheep.

Kazakh sheep are typical seasonal estrus animals. Their reproductive system regulation mainly involves the complex regulation of the hypothalamic-pituitary-gonadal axis (HPGA), which is also closely related to reproductive hormone secretion. Gonadotropin-releasing hormone (GnRH), synthesized and secreted by the hypothalamus, is the key to controlling sheep reproductive activity. We studied how GNAQ (G protein subunit alpha q) regulates estrus in sheep by controlling GnRH expression and secretion. We used hypothalamic nerve cells as the research model. GNAQ overexpression and RNA interference vectors were constructed and transfected into the hypothalamic nerve cells of fetal Kazakh sheep. qPCR, western blotting, and enzyme-linked immunosorbent assay were used to detect GNAQ gene expression in Kazakh ewe tissues and analyze its regulatory effect on GnRH expression in the hypothalamic nerve cells. The fetal sheep hypothalamic nerve cells were successfully isolated and cultured. qPCR and cell immunofluorescence showed that the purity of positive cells was >95%. The tissue expression profile showed that there were different degrees of GNAQ gene expression in the Kazakh ewe tissue. Expression levels were relatively higher in the hypothalamus, pituitary, brain, and uterine tissues. When GNAQ expression was downregulated in the hypothalamic nerve cells, the upstream genes KISS1 (kisspeptin), GPR54 (KISS1 receptor), and ER (estrogen receptor) were all upregulated, as were the downstream genes PLCB1 (phospholipase C beta 1), PRKCB (protein kinase C beta), and GNRH. At the same time, GnRH secretion levels were also upregulated. GNAQ regulated its downstream gene PLCB1 in the hypothalamic nerve cells, and directly regulated GnRH expression and secretion through the calcium and PRKC signaling pathways. GNAQ also regulated kisspeptin expression, subsequently regulating GnRH expression and secretion indirectly through the kisspeptin-GPR54 signaling pathway. Our results are of great importance for improving the reproductive performance of seasonal-estrus sheep.

A Facile, Protein-Derived Supramolecular Theranostic Strategy for Multimodal-Imaging-Guided Photodynamic and Photothermal Immunotherapy In Vivo.

Theranostic systems that permit both diagnosis and treatment in vivo are highly appealing means by which to meet the demands of precision medicine. However, most such systems remain subject to issues related to complex molecular design and synthesis, potential toxicity, and possible photoactivity changes. Herein, a novel supramolecular theranostic strategy involving biomarker protein activation (BPA) and a host-guest strategy is proposed. To exemplify BPA, a facile "one-for-all" nanotheranostic agent for both albumin detection and cancer treatment is demonstrated, which utilizes a nanoparticulate heavy-atom-free BODIPY dye derivative (B4 NPs). The fluorescence and photoactivity of BODIPY dyes are completely suppressed by aggregation-induced self-quenching in the nanoparticulate state. However, a Balb/c nude mouse model is used to confirm that following the disassembly of injected B4 NPs, BODIPY specifically binds albumin in vivo, accompanied by significantly enhanced biocompatibility and photothermal conversion efficiency. More importantly, this supramolecular host-guest BPA strategy enables the resultant nanoplatform to act as a facile and efficient strategy for photodynamic and photothermal immunotherapy.