A tripartite rheostat controls self-regulated host plant resistance to insects.

Plants deploy receptor-like kinases and nucleotide-binding leucine-rich repeat receptors to confer host plant resistance (HPR) to herbivores1. These gene-for-gene interactions between insects and their hosts have been proposed for more than 50 years2. However, the molecular and cellular mechanisms that underlie HPR have been elusive, as the identity and sensing mechanisms of insect avirulence effectors have remained unknown. Here we identify an insect salivary protein perceived by a plant immune receptor. The BPH14-interacting salivary protein (BISP) from the brown planthopper (Nilaparvata lugens Stål) is secreted into rice (Oryza sativa) during feeding. In susceptible plants, BISP targets O. satvia RLCK185 (OsRLCK185; hereafter Os is used to denote O. satvia-related proteins or genes) to suppress basal defences. In resistant plants, the nucleotide-binding leucine-rich repeat receptor BPH14 directly binds BISP to activate HPR. Constitutive activation of Bph14-mediated immunity is detrimental to plant growth and productivity. The fine-tuning of Bph14-mediated HPR is achieved through direct binding of BISP and BPH14 to the selective autophagy cargo receptor OsNBR1, which delivers BISP to OsATG8 for degradation. Autophagy therefore controls BISP levels. In Bph14 plants, autophagy restores cellular homeostasis by downregulating HPR when feeding by brown planthoppers ceases. We identify an insect saliva protein sensed by a plant immune receptor and discover a three-way interaction system that offers opportunities for developing high-yield, insect-resistant crops.

FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer.

Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT-PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK-8 assay, flow cytometry, wound-healing assay, Transwell assay, and Co-IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.

An insight into the gut microbiota after Schistosoma japonicum eggs immunization in an experimental ulcerative colitis model.

Schistosome infection and schistosome-derived products have been implicated in the prevention and alleviation of inflammatory bowel disease by manipulating the host immune response, whereas the role of gut microbiota in this protective effect remains poorly understood. In this study, we found that the intraperitoneal immunization with Schistosoma japonicum eggs prior to dextran sulfate sodium (DSS) application significantly ameliorated the symptoms of DSS-induced acute colitis, which was characterized by higher body weight, lower disease activity index score and macroscopic inflammatory scores. We demonstrated that the immunomodulatory effects of S. japonicum eggs were accompanied by an influence on gut microbiota composition, abundance, and diversity, which increased the abundance of genus Turicibacter, family Erysipelotrichaceae, phylum Firmicutes, and decreased the abundance of genus Odoribacter, family Marinifilaceae, order Bacteroidales, class Bacteroidia, phylum Bacteroidota. In addition, Lactobacillus was identified as a biomarker that distinguishes healthy control mice from DSS-induced colitis mice. The present study revealed the importance of the gut microbiota in S. japonicum eggs exerting protective effects in an experimental ulcerative colitis (UC) model, providing an alternative strategy for the discovery of UC prevention and treatment drugs.

Molecular oxidation-reduction junctions for artificial photosynthetic overall reaction.

Constructing redox semiconductor heterojunction photocatalysts is the most effective and important means to complete the artificial photosynthetic overall reaction (i.e., coupling CO2 photoreduction and water photo-oxidation reactions). However, multiphase hybridization essence and inhomogeneous junction distribution in these catalysts extremely limit the diverse design and regulation of the modes of photogenerated charge separation and transfer pathways, which are crucial factors to improve photocatalytic performance. Here, we develop molecular oxidation-reduction (OR) junctions assembled with oxidative cluster (PMo12, for water oxidation) and reductive cluster (Ni5, for CO2 reduction) in a direct (d-OR), alternant (a-OR), or symmetric (s-OR) manner, respectively, for artificial photosynthesis. Significantly, the transfer direction and path of photogenerated charges between traditional junctions are obviously reformed and enriched in these well-defined crystalline catalysts with monophase periodic distribution and thus improve the separation efficiency of the electrons and holes. In particular, the charge migration in s-OR shows a periodically and continuously opposite mode. It can inhibit the photogenerated charge recombination more effectively and enhance the photocatalytic performance largely when compared with the traditional heterojunction models. Structural analysis and density functional theory calculations disclose that, through adjusting the spatial arrangement of oxidation and reduction clusters, the energy level and population of the orbitals of these OR junctions can be regulated synchronously to further optimize photocatalytic performance. The establishment of molecular OR junctions is a pioneering important discovery for extremely improving the utilization efficiency of photogenerated charges in the artificial photosynthesis overall reaction.

Stable Low-Temperature Al Batteries Enabled by Integrating Polydopamine-Derived N-Doped Carbon Nanospheres With Flake Graphite.

The battery performance declines significantly in severely cold areas, especially discharge capacity and cycle life, which is the most significant pain point for new energy consumers. To address this issue and improve the low-temperature characteristic of aluminum-ion batteries, in this work, polydopamine-derived N-doped carbon nanospheres are utilized to modify the most promising graphite material. More active sites are introduced into graphite, more ion transport channels are provided, and improved ionic conductivity is achieved in a low-temperature environment. Due to the synergistic effect of the three factors, the ion diffusion resistance is significantly reduced and the diffusion coefficient of aluminum complex ions in the active material become larger at low temperatures. Therefore, the battery delivers an improved capacity retention rate from 23% to 60% at -20 °C and excellent ultra-long cycling stability over 5500 cycles at -10 °C. This provides a novel strategy for constructing low-temperature aluminum-ion batteries with high energy density, which is conducive to promoting the practicality of aluminum-ion batteries.

Room-Temperature High-Performance Photodetector and Phototransistor Based on PdSe2/ZnIn2S4 Alloy Heterojunctions.

Various semiconductor devices have been developed based on 2D heterojunction materials owing to their distinctive optoelectronic properties. However, to achieve efficient charge transfer at their interface remains a major challenge. Herein, an alloy heterojunction concept is proposed. The sulfur vacancies in ZnIn2S4 are filled with selenium atoms of PdSe2. This chemically bonded heterojunction can significantly enhance the separation of photocarriers, providing notable advantages in the field of photoelectric conversion. As a demonstration, a two-terminal photodetector based on the PdSe2/ZnIn2S4 heterojunction materials is fabricated. The photodetector exhibits stable operation in ambient conditions, showcasing superior performance in terms of large photocurrent, high responsivity (48.8 mA W-1) and detectivity (1.98 × 1011 Jones). To further validate the excellent optoelectronic performance of the heterojunction, a tri-terminal phototransistor is also fabricated. Benefiting from gate voltage modulation, the photocurrent is amplified to milliampere level, and the responsivity is increased to 229.14 mA W-1. These findings collectively demonstrate the significant potential of the chemically bonded PdSe2/ZnIn2S4 alloy heterojunction for future optoelectronic applications.

GluN2A: A Promising Target for Developing Novel Antidepressants.

BACKGROUND: Depression is a heterogeneous disorder with high morbidity and disability rates that poses serious problems regarding mental health care. It is now well established that N-methyl D-aspartate receptor (NMDAR) modulators are being increasingly explored as potential therapeutic options for treating depression, although relatively little is known about their mechanisms of action. NMDARs are glutamate-gated ion channels that are ubiquitously expressed in the central nervous system (CNS), and they have been shown to play key roles in excitatory synaptic transmission. GluN2A, the predominant Glu2N subunit of functional NMDARs in neurons, is involved in various physiological processes in the CNS and is associated with diseases such as anxiety, depression, and schizophrenia. However, the role of GluN2A in the pathophysiology of depression has not yet been elucidated. METHODS: We reviewed several past studies to better understand the function of GluN2A in depression. Additionally, we also summarized the pathogenesis of depression based on the regulation of GluN2A expression, particularly its interaction with neuroinflammation and neurogenesis, which has received considerable critical attention and is highly implicated in the onset of depression. RESULTS: These evidence suggests that GluN2A overexpression impairs structural and functional synaptic plasticity, which contributes to the development of depression. Consequently, this knowledge is vital for the development of selective antagonists targeting GluN2A subunits using pharmacological and molecular methods. CONCLUSIONS: Specific inhibition of the GluN2A NMDAR subunit is resistant to chronic stress-induced depressive-like behaviors, making them promising targets for the development of novel antidepressants.

MiR-182-5p: A Novel Biomarker in the Treatment of Depression in CSDS-Induced Mice.

BACKGROUND: Depression is a neuropsychiatric disease with a high disability rate and mainly caused by the chronic stress or genetic factors. There is increasing evidence that microRNAs (miRNAs) play a critical role in the pathogenesis of depression. However, the underlying molecular mechanism for the pathophysiology of depression of miRNA remains entirely unclear so far. METHODS: We first established a chronic social defeat stress (CSDS) mice model of depression, and depression-like behaviors of mice were evaluated by a series of behavioral tests. Next, we detected several abundantly expressive miRNAs suggested in previous reports to be involved in depression and found miR-182-5p was selected as a candidate for analysis in the hippocampus. Then western blotting and immunofluorescence were used together to examine whether adeno-associated virus (AAV)-siR-182-5p treatment alleviated chronic stress-induced decrease in hippocampal Akt/GSK3ß/cAMP-response element binding protein (CREB) signaling pathway and increase in neurogenesis impairment and neuroinflammation. Furthermore, CREB inhibitor was adopted to examine if blockade of Akt/GSK3ß/CREB signaling pathway abolished the antidepressant actions of AAV-siR-182-5p in mice. RESULTS: Knockdown of miR-182-5p alleviated depression-like behaviors and impaired neurogenesis of CSDS-induced mice. Intriguingly, the usage of agomiR-182-5p produced significant increases in immobility times and aggravated neuronal neurogenesis damage of mice. More importantly, it suggested that 666-15 blocked the reversal effects of AAV-siR-182-5p on the CSDS-induced depressive-like behaviors in behavioral testing and neuronal neurogenesis within hippocampus of mice. CONCLUSIONS: These findings indicated that hippocampal miR-182-5p/Akt/GSK3ß/CREB signaling pathway participated in the pathogenesis of depression, and it might give more opportunities for new drug developments based on the miRNA target in the clinic.

PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?

Economic development and increased stress have considerably increased the prevalence of psychiatric disorders in recent years, which rank as some of the most prevalent diseases globally. Several factors, including chronic social stress, genetic inheritance, and autogenous diseases, lead to the development and progression of psychiatric disorders. Clinical treatments for psychiatric disorders include psychotherapy, chemotherapy, and electric shock therapy. Although various achievements have been made researching psychiatric disorders, the pathogenesis of these diseases has not been fully understood yet, and serious adverse effects and resistance to antipsychotics are major obstacles to treating patients with psychiatric disorders. Recent studies have shown that the mammalian target of rapamycin (mTOR) is a central signaling hub that functions in nerve growth, synapse formation, and plasticity. The PI3K-AKT/mTOR pathway is a critical target for mediating the rapid antidepressant effects of these pharmacological agents in clinical and preclinical research. Abnormal PI3K-AKT/mTOR signaling is closely associated with the pathogenesis of several neurodevelopmental disorders. In this review, we focused on the role of mTOR signaling and the related aberrant neurogenesis in psychiatric disorders. Elucidating the neurobiology of the PI3K-AKT/mTOR signaling pathway in psychiatric disorders and its actions in response to antidepressants will help us better understand brain development and quickly identify new therapeutic targets for the treatment of these mental illnesses.

Microbiological characteristics of the lower airway in adults with bronchiectasis: a prospective cohort study.

BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.

The impact of MIF deficiency on alterations of fecal microbiota in C57BL/6 mice induced by Trichinella spiralis infection.

Trichinellosis caused by Trichinella spiralis (T. spiralis) is a major food-borne parasitic zoonosis worldwide. Prevention of trichinellosis is an effective strategy to improve patient quality of life. Macrophage migration inhibitory factor (MIF) is closely related to the occurrence and development of several parasitic diseases. Studying the impact of MIF deficiency (Mif-/- ) on the alterations in host fecal microbiota due to T. spiralis infection may contribute to proposing a novel dual therapeutic approach for trichinellosis. To reveal the diversity and differences in fecal microbial composition, feces were collected from T. spiralis-uninfected and T. spiralis-infected wild-type (WT) and MIF knockout (KO) C57BL/6 mice at 0, 7, 14, and 35 days post-infection (dpi), and the samples were sent for 16S rRNA amplicon sequencing on the Illumina NovaSeq platform. Flow cytometry was used to determine the expression levels of IFN-γ and IL-4 in the CD4+ /CD8+ T-cell sets of mouse spleens. The results showed that operational taxonomic unit (OTU) clustering, relative abundance of microbial composition, alpha diversity, and beta diversity exhibited significant changes among the eight groups. The LEfSe analysis selected several potential biomarkers at the genus or species level, including Akkermansia muciniphila, Lactobacillus murinus, Coprococcus catus, Firmicutes bacterium M10_2, Parabacteroides sp. CT06, and Bacteroides between the KTs and WTs groups. The predicted bacterial functions of the fecal microbiota were mainly involved in metabolism, such as the metabolism of carbohydrates, amino acids, energy, cofactors, vitamins, nucleotides, glycans, and lipids. Flow cytometry revealed an increased CD3+ CD8- /CD3+ CD8+ T-cell ratio and increased IFN-γ and IL-4 levels in CD3+ CD8- T-cell sets from WT and MIF KO mice at 7 dpi. The results indicated that both MIF KO and infection time have a significant influence on the CD3+ CD8- IFN-γ+ and CD3+ CD8- IL-4+ response in mice after T. spiralis. In conclusion, this research showed alterations of the fecal microbiota and immune response in both WT and MIF KO mice before and after T. spiralis infection. These results revealed a potential role of MIF in regulating the pathogenesis of trichinellosis related to the intestinal microbiota. Importantly, the selected potential biomarkers combined with MIF will also offer a novel therapeutic approach to treat trichinellosis in the future.

Origin of Manipulating Selectivity in Prins Cyclization by [Ga4L6]12- Supramolecular Catalysis through Host-Guest Interactions.

The host effect of the supramolecular [Ga4L6]12- tetrahedral metallocage on Prins cyclization reaction of the substrate by encapsulated citronellal has been investigated by means of molecular dynamics and quantum mechanics. The encapsulation process of the substrate into the [Ga4L6]12- cavity was simulated via attach-pull-release (APR) methods. Thermodynamic calculations and classical molecular dynamics simulations assessed the substrate's microenvironment inside the cavity, guiding DFT-level modeling of the reaction. DFT calculations show diol product predominance in acidic solution but high enol selectivity inside [Ga4L6]12-, consistent with experimental findings. [Ga4L6]12- alters the selectivity of the Prins cyclization reaction by inhibiting diol formation. The activation strain model-based decomposition analysis (ASM-DA) of the barrier difference among distortion and interaction terms indicates that the more positive interaction between a host and guest in the diol transition state than enol determines the product selectivity, particularly the fewer C-H···O and O-H···O hydrogen-bonding interactions. These theoretical insights could contribute to a deeper understanding of the nature of supramolecular catalysis and to further develop new supramolecular catalysts.

Recent advances in the natural product analogues for the treatment of neurodegenerative diseases.

Neurodegenerative diseases (NDs) represent a hallmark of numerous incapacitating and untreatable conditions, the incidence of which is escalating swiftly, exemplified by Alzheimer's disease and Parkinson's disease. There is an urgent necessity to create pharmaceuticals that exhibit high efficacy and minimal toxicity in order to address these debilitating diseases. The structural complexity and diversity of natural products confer upon them a broad spectrum of biological activities, thereby significantly contributing to the history of drug discovery. Nevertheless, natural products present challenges in drug discovery, including time-consuming separation processes, low content, low bioavailability, and other related issues. To address these challenges, numerous analogs of natural products have been synthesized. This methodology enables the rapid synthesis of analogs of natural products with the potential to serve as lead compounds for drug development, thereby paving the way for the discovery of novel pharmaceuticals. This paper provides a summary of 127 synthetic analogues featuring various natural product structures, including flavonoids, alkaloids, coumarins, phenylpropanoids, terpenoids, polyphenols, and amides. The compounds are categorized based on their efficacy in treating various diseases. Furthermore, this article delves into the structure-activity relationship (SAR) of certain analogues, offering a thorough point of reference for the systematic development of pharmaceuticals aimed at addressing neurodegenerative conditions.

Circulating metabolites of Borneolum syntheticum (Bingpian) ameliorate atherosclerosis in ApoE-/- mice via inhibiting macrophage foam-cell formation.

Translational pharmacological research on traditional medicines lays the foundation for precisely understanding how the medicines function in the body to deliver therapeutic benefits. Borneolum syntheticum (Bingpian) is commonly used in Chinese herbal medicines for coronary heart disease, but its specific cardiovascular impact remains poorly understood. Isoborneol, a constituent of Bingpian, has been found to reduce lipid accumulation in macrophages in vitro, but its oral bioavailability is limited. This investigation aimed to evaluate anti-atherosclerotic effects of Bingpian, based on understanding its first-pass metabolism. Human subjects orally received an herbal medicine containing Bingpian and their plasma samples were analyzed to identify the major circulating compounds of Bingpian, with the metabolism that was also characterized in vitro and in mice. The identified compounds were evaluated for their ability to inhibit macrophage foam-cell formation induced by oxidized low-density lipoprotein. Furthermore, the anti-atherosclerotic effect of repeatedly dosed Bingpian was assessed in ApoE-/- mice fed a high-fat diet. In human subjects, the major circulating compounds of Bingpian were metabolites, rather than their precursor constituents borneol and isoborneol. These constituents were efficiently absorbed in the intestinal tract but underwent significant first-pass metabolism, involving UGT2B7-mediated glucuronidation into borneol-2-O-glucuronide and isoborneol-2-O-glucuronide, respectively, and CYP2A6/2B6/3A-mediated oxidation both into camphor. Despite their poor membrane permeability, hepatic efflux of borneol-2-O-glucuronide and isoborneol-2-O-glucuronide into the systemic circulation was enhanced by MRP3/4. The circulating metabolites, particularly their combinations, markedly inhibited macrophage foam-cell formation induced by oxidized low-density lipoprotein in vitro. Sub-chronic administration of Bingpian (30 mg·kg-1·d-1, i.g.) for 12 weeks significantly decreased atherosclerotic lesion size and enhanced plaque stability in ApoE-/- mice. Systemic exposure to Bingpian metabolites in mice closely resembles that in humans, suggesting that the pharmacodynamic effects of Bingpian in mice are likely applicable to humans. Overall, the cardiovascular benefits of Bingpian involve reducing atherosclerosis by inhibiting foam-cell formation through its metabolites. This investigation supports that oral Bingpian could be a druggable agent for reducing atherosclerosis.

Scalp cooling therapy for chemotherapy-induced hair loss in patients with breast or gynecological cancers-an Asian tertiary institution experience.

PURPOSE: Scalp cooling therapy (SCT) improves chemotherapy-induced alopecia (CIA), but there are few published data about its efficacy in an Asian-predominant population. We report our tertiary institution experience of SCT in patients with breast or gynaecological cancers undergoing chemotherapy. METHODS: The Paxman scalp cooling system was employed for eligible women with breast or gynaecological cancers receiving anthracycline or taxane-based chemotherapy. Only patients with Grade (G) 0-1 alopecia by common terminology criteria for adverse events (CTCAE) version 4.0 were eligible initially, but patients with G2 alopecia were later included in the study. SCT was performed at each chemotherapy cycle, commencing 30 min prior to and continuing up to 90 min after completion of the drug infusion. Patients were assessed at the start and end of each session for hair preservation (defined as G0-2 alopecia) and comfort level of SCT (rated on a 5-point visual scale). The primary end point was success of hair preservation or hair regrowth after completion of all cycles of chemotherapy. RESULTS: Eighty-three patients were enrolled over a period of 18 months from December 2017 to October 2019, with a total of 510 scalp cooling cycles performed. 94.0% (n = 78) of patients reported a comfort score of 3 and above, indicating that the procedure was comfortable, upon a 5-point visual scale. Patients receiving weekly paclitaxel had highest success in hair preservation at 76.7% (23/30 patients), with a lower rate of hair preservation observed for the 3 weekly paclitaxel regimen (50%, 2/4 patients). In contrast, only 1 patient (5.3%, 1/19 patients) who underwent chemotherapy with anthracycline and cyclophosphamide achieved hair preservation. CONCLUSION: SCT is well tolerated in an Asian-predominant population. Among women with breast or gynaecological cancers receiving taxane and/or anthracycline based chemotherapy, those who underwent SCT were about 50% more likely to achieve hair preservation or hair regrowth, as compared to historical controls.

Management of renal sinus angiomyolipoma: modified robotic nephron-sparing surgery in a single center.

BACKGROUND: Renal sinus angiomyolipoma (RSAML) is a rare and typically complex renal tumor. The objective is to present our single-center experience with a modified technique of robotic nephron-sparing surgery (NSS) for treating RSAML. METHODS: We retrospectively evaluated 15 patients with RSAMLs who were treated with robotic NSS at the Department of Urology of Tongji hospital, ranging from November 2018 to September 2022. Renal vessels and ureter were dissected. The outer part of RSAML was resected. The rest of tumor was removed by bluntly grasp, curettage and suction. Absorbable gelatin sponges were filled in the renal sinus. The preoperative parameters, operative measures and postoperative outcomes were all collected. Follow-up was performed by ultrasonography and estimated glomerular filtration rate (eGFR). RESULTS: Robotic NSS was successfully performed in all the patients, without any conversion to open surgery or nephrectomy. The mean operation time was 134.13 ± 40.56 min. The mean warm ischemia time was 25.73 ± 3.28 min. The median estimated blood loss was 100 [50, 270] ml and 1 patient required blood transfusion. The mean drainage duration was 5.77 ± 1.98 days. The median postoperative hospital stay was 6.90 [5.80, 8.70] days. Two patients experienced postoperative urinary tract infection (Clavien-Dindo Grade II). During the median follow-up of 25.53 ± 15.28 months, patients received 91.18% renal function preservation. No local recurrence occurred in all the patients. CONCLUSIONS: Robotic NSS for RSAML is a complicated procedure that demands technical expertise and a well-designed strategy is critical in the operation. Treating RSAML with modified robotic NSS is safe, effective and feasible.

Tandem mass tag-based proteomics reveals the antiepileptic mechanism of steroidal saponins from Anemarrhena asphodeloides in Kainic acid induced epileptic rat model.

Epilepsy (EP) is one of the most common neurological diseases in the world. Anemarrhena asphodeloides Bunge. (AA), as a typical heat-cleaning medicine, has been proven to possess the antiepileptic effect in clinical and experimental studies. Anemarrhena asphodeloides steroidal saponins (AAS) are main components. However, the therapeutic effects and underlying mechanisms of AAS against EP are not been fully elucidated. In this study, 63 steroidal saponins were discovered in AAS by UPLC-Q-TOF/MS analysis. Pharmacological and behavioral analysis demonstrated that AAS could significantly lower the Racine classification and reduce the frequency of generalized spike rhythm the rate of tetanic seizures in kainic acid-induced epileptic rats. Hematoxylin and eosin and Nissl staining-indicated AAS could significantly improve hippocampal injury and neuron loss in epileptic rats. TMT proteomic analysis discovered 26 different expressed proteins (DEPs), which were identified as the rescue proteins. After bioinformatic analysis, Heat Shock Protein 90 Alpha Family Class B Member 1 (Hsp90ab1) and Tyrosine 3-Monooxygenase (Ywhab) were screened as key DEPs and verified by western blotting. AAS could significantly inhibited the up-regulation of Hsp90ab1 and Ywhab in EP rats; these two proteins might be the key targets of AAS in treating EP.

Luteolin: A promising multifunctional natural flavonoid for human diseases.

Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It is noteworthy that LUT exhibits a variety of beneficial pharmacological properties and holds significant potential for clinical applications, particularly in antitumor, anti-convulsion, diabetes control, anti-inflammatory, neuroprotection, anti-oxidation, anti-cardiovascular, and other aspects. The potential mechanism of action has been partially elucidated, including the mediation of NF-κB, toll-like receptor, MAPK, Wnt/ß-catenin, PI3K/Akt, AMPK/mTOR, and Nrf-2, among others. The review that aimed to comprehensively consolidate essential information on natural sources, pharmacological effects, therapeutic and preventive potential, as well as potential mechanisms of LUT. The objective is to establish a theoretical basis for the continued development and application of LUT.

Cytotoxic withanolides from the leaves of Datura stramonium L.

Six novel withanolides, along with nine known related compounds were isolated from the leaves of Datura stramonium L. The structures and absolute configurations of the new withanolides were elucidated by employing various spectral techniques and comparing them with those previously reported in the literature. In addition, four withanlides demonstrated interesting cytotoxic activity on LN229 cells with IC50 <20 µM.

Experimental Study of Electroosmosis in Rock Cores Based on the Dual Pressure Sensor Method.

Electroosmotic experiments obtain the electroosmotic pressure coefficient of a rock sample by measuring the excitation voltage at both ends of the sample and the pressure difference caused by the excitation voltage. The electroosmotic pressure is very weak and buried in the background noise, which is the most difficult signal to measure in the dynamic-electric coupling experiment, so it is necessary to improve its signal-to-noise ratio. In this paper, for the low signal-to-noise ratio of electroosmotic pressure, the dual pressure sensor method is proposed, i.e., two pressure sensors of the same type are used to measure electroosmotic pressure. Two different data extraction methods, Fast Fourier Transform and Locked Amplification, are utilized to compare the dual pressure sensor method of this paper with the existing single pressure sensor method. The relationship between the electroosmotic pressure coefficient and the excitation frequency, mineralization, permeability, and porosity is analyzed and discussed.