Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits.

Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

Aggf1 Specifies Hemangioblasts at the Top of Regulatory Hierarchy via Npas4l and mTOR-S6K-Emp2-ERK Signaling.

BACKGROUND: Hemangioblasts are mesoderm-derived multipotent stem cells for differentiation of all hematopoietic and endothelial cells in the circulation system. However, the underlying molecular mechanism is poorly understood. METHODS: CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (type II CRISPR RNA-guided endonuclease) editing was used to develop aggf1-/- and emp2-/- knockout zebra fish. Whole-mount in situ hybridization and transgenic Tg(gata1-EGFP [enhanced green fluorescent protein]), Tg(mpx-EGFP), Tg(rag2-DsRed [discosoma sp. red fluorescent protein]), Tg(cd41-EGFP), Tg(kdrl-EGFP), and Tg(aggf1-/-;kdrl-EGFP) zebra fish were used to examine specification of hemangioblasts and hematopoietic stem and progenitor cells (HSPCs), hematopoiesis, and vascular development. Quantitative real-time polymerase chain reaction and Western blot analyses were used for expression analysis of genes and proteins. RESULTS: Knockout of aggf1 impaired specification of hemangioblasts and HSPCs, hematopoiesis, and vascular development in zebra fish. Expression of npas4l/cloche-the presumed earliest marker for hemangioblast specification-was significantly reduced in aggf1-/- embryos and increased by overexpression of aggf1 in embryos. Overexpression of npas4l rescued the impaired specification of hemangioblasts and HSPCs and development of hematopoiesis and intersegmental vessels in aggf1-/- embryos, placing aggf1 upstream of npas4l in hemangioblast specification. To identify the underlying molecular mechanism, we identified emp2 as a key aggf1 downstream gene. Similar to aggf1, emp2 knockout impaired the specification of hemangioblasts and HSPCs, hematopoiesis, and angiogenesis by increasing the phosphorylation of ERK1/2 (extracellular signal-regulated protein kinase 1/2). Mechanistic studies showed that aggf1 knockdown and knockout significantly decreased the phosphorylated levels of mTOR (mammalian target of rapamycin) and p70 S6K (ribosomal protein S6 kinase), resulting in reduced protein synthesis of Emp2 (epithelial membrane protein 2), whereas mTOR activator MHY1485 (4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine) rescued the impaired specification of hemangioblasts and HSPCs and development of hematopoiesis and intersegmental vessels and reduced Emp2 expression induced by aggf1 knockdown. CONCLUSIONS: These results indicate that aggf1 acts at the top of npas4l and becomes the earliest marker during specification of hemangioblasts. Our data identify a novel signaling axis of Aggf1 (angiogenic factor with G-patch and FHA domain 1)-mTOR-S6K-ERK1/2 for specification of hemangioblasts and HSPCs, primitive and definitive hematopoiesis, and vascular development. Our findings provide important insights into specification of hemangioblasts and HSPCs essential for the development of the circulation system.

Cholecystokinin-like peptide mediates satiety by inhibiting sugar attraction.

Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. Interestingly, we found that one of the two known SK receptors, CCKLR-17D3, is expressed by some of Gr64f-expressing neurons in the proboscis and proleg tarsi. Thus, we have identified SK as a neuropeptide signal in a neuronal circuitry that responds to food intake, and regulates feeding behavior by diminishing gustatory receptor gene expression and activity of sweet sensing GRNs. Our findings demonstrate one nutritional state-dependent pathway that modulates sweet perception and thereby feeding behavior, but our experiments cannot exclude further parallel pathways. Importantly, we show that the underlying mechanisms are conserved in the two distantly related insect species.

Cadmium/zinc stresses and plant cultivation influenced soil microflora: a pot experiment conducted in field.

It's of great challenge to address for heavy metal-contaminated soil. Once the farmland is contaminated with heavy metals, the microbial ecology of the plant rhizosphere will change, which in turn impacts crop productivity and quality. However, few studies have explored the effects of heavy metals on plant rhizosphere microbes in farmland and the role that plant cultivation plays in such a phytoremediation practice. In this study, the impacts of comfrey (Symphytum officinale L.) cultivation and the stresses of cadmium/zinc (Cd/Zn) on rhizosphere soil microflora were examined. Microbial DNA was collected from soils to evaluate the prevalence of bacteria and fungi communities in rhizosphere soils. High-throughput 16 S rRNA sequencing was used to determine the diversity of the bacterial and fungal communities. The results showed that growing comfrey on polluted soils reduced the levels of Cd and Zn from the vertical profile. Both the comfrey growth and Cd/Zn stresses affected the community of rhizosphere microorganisms (bacteria or fungi). Additionally, the analysis of PCoA and NMDS indicated that the cultivation of comfrey significantly changed the bacterial composition and structure of unpolluted soil. Comfrey cultivation in polluted and unpolluted soils did not result in much variance in the fungi's species composition, but the fungal compositions of the two-type soils were noticeably different. This work provided a better understanding of the impacts of Cd/Zn stresses and comfrey cultivation on rhizosphere microbial community, as well as new insight into phytoremediation of heavy metal-contaminated soils.

Comparison of craniomaxillofacial morphology in children with unilateral cleft lip and palate treated with/without presurgical nasoalveolar molding - a retrospective study with a mean age of 5 years.

OBJECTIVES: To three-dimensionally assess differences in craniomaxillofacial skeletal development in patients with operated unilateral cleft lip and palate (UCLP) treated with/without presurgical nasoalveolar molding (PNAM) with a mean age of 5 years. MATERIALS AND METHODS: Cone-beam CT radiographs of 30 patients with UCLP who had undergone PNAM and 34 patients with UCLP who did not receive PNAM were analyzed. The data were stored in DICOM file format and were imported into the Dolphin Imaging program for 3D image reconstruction and landmark identification. 33 landmarks, 17 linear and three angular variables representing craniofacial morphology were analyzed and compared by using the Mann-Whitney U tests. RESULTS: The vast majority of linear variables and 3D coordinates of landmark points reflecting craniofacial skeletal symmetry were not significantly different between the two groups. In terms of craniofacial skeletal development, the PNAM group had a significantly smaller anterior nasal spine offset in the midsagittal plane and a greater maxillary length compared to the non-PNAM group. CONCLUSIONS: Evaluations performed in early childhood showed that treatment with/without PNAM in the neonatal period was not a major factor influencing craniomaxillofacial hard tissue development in patients with UCLP; moreover, PNAM treatment showed significant correction of skeletal deviation at the base of the nose. CLINICAL RELEVANCE: Follow-up in early childhood has shown that PNAM treatment administered during the neonatal stage does not impede maxillary development and has benefits in correcting nasal floor deviation. It is a viable option for improving nasal deformity in children with unilateral cleft lip and palate.

Fully digital workflow of occlusal reconstruction treatment in a patient with congenital dentition defects.

OBJECTIVE: Occlusal reconstruction is a critical intervention for patients with dental hard tissue defects, temporomandibular joint (TMJ) disorders, and jaw position abnormalities. Clinical efficiency and outcomes of these procedures have improved with advances in digital technologies. This case report aims to illustrate a comprehensive digital workflow for occlusal reconstruction in a patient with congenital dentition defects, emphasizing the application of digital technologies to enhance treatment outcomes. CLINICAL CONSIDERATIONS: A 28-year-old woman with previously installed porcelain-fused-to-metal bridge restorations presented with a fractured prosthesis and TMJ symptoms. A multidisciplinary approach was adopted involving the use of digital facebow, intraoral scanners, digital smile design, and CAD/CAM technologies. The process included the extraction of defective restorations, temporary restorations to refine jaw position, and final permanent restorations. The digital workflow facilitated precise diagnostics and treatment, culminating in the successful installation of permanent restorations. Regular follow-ups at one- and three-months post-treatment confirmed stable occlusal function and high patient satisfaction. CONCLUSIONS: This case report showcases the potential of multiple digital technologies to streamline complex dental treatments and achieve high-quality results. CLINICAL SIGNIFICANCE: The integration of digital technologies in occlusal reconstruction treatments offers significant benefits in terms of precision, patient comfort, and esthetic outcomes.

The dynamic features and microbial mechanism of nitrogen transformation for hydrothermal aqueous phase as fertilizer in dryland soil.

Hydrothermal aqueous phase (HAP) contains abundant organics and nutrients, which have potential to partially replace chemical fertilizers for enhancing plant growth and soil quality. However, the underlying reasons for low available nitrogen (N) and high N loss in dryland soil remain unclear. A cultivation experiment was conducted using HAP or urea to supply 160 mg N kg-1 in dryland soil. The dynamic changes of soil organic matters (SOMs), pH, N forms, and N cycling genes were investigated. Results showed that SOMs from HAP stimulated urease activity and ureC, which enhanced ammonification in turn. The high-molecular-weight SOMs relatively increased during 5-30 d and then biodegraded during 30-90 d, which SUV254 changed from 0.51 to 1.47 to 0.29 L-1 m-1. This affected ureC that changed from 5.58 to 5.34 to 5.75 lg copies g-1. Relative to urea, addition HAP enhanced ON mineralization by 8.40 times during 30-90 d due to higher ureC. It decreased NO3-N by 65.35%-77.32% but increased AOB and AOA by 0.25 and 0.90 lg copies g-1 at 5 d and 90 d, respectively. It little affected nirK and increased nosZ by 0.41 lg copies g-1 at 90 d. It increased N loss by 4.59 times. The soil pH for HAP was higher than that for urea after 11 d. The comprehensive effects of high SOMs and pH, including ammonification enhancement and nitrification activity inhibition, were the primary causes of high N loss. The core idea for developing high-efficiency HAP fertilizer is to moderately inhibit ammonification and promote nitrification.

The Involvement of Ascorbic Acid in Cancer Treatment.

Vitamin C (VC), also known as ascorbic acid, plays a crucial role as a water-soluble nutrient within the human body, contributing to a variety of metabolic processes. Research findings suggest that increased doses of VC demonstrate potential anti-tumor capabilities. This review delves into the mechanisms of VC absorption and its implications for cancer management. Building upon these foundational insights, we explore modern delivery systems for VC, evaluating its use in diverse cancer treatment methods. These include starvation therapy, chemodynamic therapy (CDT), photothermal/photodynamic therapy (PTT/PDT), electrothermal therapy, immunotherapy, cellular reprogramming, chemotherapy, radiotherapy, and various combination therapies.

Bioinspired Environment-Adaptable and Ultrasensitive Multifunctional Electronic Skin for Human Healthcare and Robotic Sensations.

Multifunctional electronic skins (e-skins) that can sense various stimuli have demonstrated increasing potential in many fields. However, most e-skins are human-oriented that cannot work in hash environments such as high temperature, underwater, and corrosive chemicals, impairing their applications, especially in human-machine interfaces, intelligent machines, robotics, and so on. Inspired by the crack-shaped sensory organs of spiders, an environmentally robust and ultrasensitive multifunctional e-skin is developed. By developing a polyimide-based metal crack-localization strategy, the device has excellent environment adaptability since polyimide has high thermal stability and chemical durability. The localized cracked part serves as an ultrasensitive strain sensing unit, while the non-cracked serpentine part is solely responsible for temperature. Since the two units are made of the same material and process, the signals are decoupled easily. The proposed device is the first multifunctional e-skin that can be used in harsh environments, therefore is of great potential for both human and robot-oriented applications.

Implication of different frailty criteria in older people with atrial fibrillation: a prospective cohort study.

BACKGROUND: the prevalence of physical and multidimensional frailty and their prognostic impact on clinical outcomes in patients with atrial fibrillation (AF) is unclear. OBJECTIVE: to evaluated frailty in a cohort of patients with AF according to different criteria, and studied the prevalence and its prognostic impact on clinical outcomes. METHODS: in this multicenter prospective cohort, 197 inpatients ≥ 65 years old with AF were recruited from September 2018 to April 2019.We used Fried Frailty phenotype (Fried) to assess physical frailty, and comprehensive geriatric assessment-frailty index (CGA-FI) to assess multidimensional frailty. The primary outcome was a composite of all-cause mortality or rehospitalization. RESULTS: the prevalence of frailty was determined as 34.5% by Fried, 42.6% by CGA-FI. Malnutrition and ≥ 7 medications were independently associated with frailty. Kaplan-Meier survival curve showed that the presence of frailty by CGA-FI had significantly lower all-cause mortality or rehospitalization survival rate (log-rank P = 0.04) within 1 year. Multivariate Cox regression adjusted for age and sex showed that the frailty by CGA-FI was significantly associated with the risk of all-cause mortality or rehospitalization within 1 year (HR 1.79, 95% CI 1.10-2.90). However, those associations were absent with the physical frailty. After broader multivariate adjustment, those associations were no longer statistically significant for both types of frailty. CONCLUSIONS: in older people with AF, Multidimensional frailty is more significantly associated with a composite of all-cause mortality or rehospitalization within 1 year than physical frailty, but these association are attenuated after multivariate adjustment. CLINICAL TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018.

Effects of water-soluble chitosan on Hylotelephium spectabile and soybean growth, as well as Cd uptake and phytoextraction efficiency in a co-planting cultivation system.

Intercropping a Cd-accumulator with economically valuable crops is common in slightly or moderately Cd-polluted farmland soils. A field experiment was conducted to evaluate the effects of water-soluble chitosan (WSC) on the growth and Cd uptake of the Cd-accumulator Hylotelephium spectabile and soybean (Glycine max) during a co-cultivation in Cd-contaminated agricultural soil (WSC, 0 and 10 g·m-2). The results indicated that soybean yields were highest in response to the intercropping and WSC treatment. The results from the field trials generally showed that intercropping and WSC treatments significantly decreased Cd concentrations in inedible parts of soybean by 42.9-72.1% (except for stems), in the meantime, increased 95.8%-334.6% in shoot and root tissues of H. spectabile compared with the control (p < 0.05). The data revealed that Cd uptake was highest for H. spectabile during the intercropping and WSC treatment. The application of WSC in the intercropping system significantly increased the uptake of Cd by H. spectabile, but not by soybean. The findings of this study suggest that combining an intercropping system with a WSC treatment may be better for remediating Cd-contaminated soils than other methods involving the growth of a single hyperaccumulator.

This paper clearly focused on the accumulation and uptake of Cd in the system of intercropping of Cd-accumulator (Hylotelephium spectable) and soybean (Glycine max) grown in Cd-polluted farmland soils supplied with water-soluble chitosan (WSC) under field conditions. Some studies mainly focused on active agent to promote remediation efficiency of (hyper) accumulators. This study indicated that combining the intercropping system with WSC may be better for remediating Cd-contaminated soils than the methods involving a single hyperaccumulator.

Sludge biodrying coupled with photocatalysis improves the degradation of extracellular polymeric substances.

The efficiency of sludge dewatering is limited by extracellular polymeric substances (EPS) during biodrying. This study investigated the effect of photocatalysis-mediated EPS degradation on sludge dewatering performance during the sludge biodrying process. The photocatalysis of municipal sludge was first carried out to choose a cost-efficient catalyst. Then sludge biodrying tests were performed using TiO2-coated amendment (TCA) and uncoated amendment (TUCA) as the control. Municipal sludge photocatalysis results showed that using TiO2 could efficiently degrade carbohydrates and proteins in the EPS within 60 min. After 20-day biodrying, photocatalysis significantly promoted a reduction in the moisture content and EPS by 17.64% and 6.88%, respectively. The surface-enhanced Raman scattering (SERS) intensities of the C-C-O symmetric stretching vibration peak of D-lactose and the C-S stretching vibration peak of cysteine were significantly decreased by approximately 33.19% and 44.76%, respectively, indicating that photocatalysis indeed promoted the reduction of polysaccharides and cysteine in the EPS, especially after the thermophilic phase. The hydrophilic amino acid content decreased by 23.02%, verifying that photocatalysis could improve EPS hydrophobicity. Consequently, municipal sludge biodrying coupled with photocatalysis promotes sludge EPS degradation and enhances sludge dewaterability, improving the efficiency of sludge biodrying.

Discovery of a Novel Ubenimex Derivative as a First-in-Class Dual CD13/Proteasome Inhibitor for the Treatment of Cancer.

The CD13 inhibitor ubenimex is used as an adjuvant drug with chemotherapy for the treatment of cancer due to its function as an immunoenhancer, but it has limitations in its cytotoxic efficacy. The proteasome inhibitor ixazomib is a landmark drug in the treatment of multiple myeloma with a high anti-cancer activity. Herein, we conjugated the pharmacophore of ubenimex and the boric acid of ixazomib to obtain a dual CD13 and proteasome inhibitor 7 (BC-05). BC-05 exhibited potent inhibitory activity on both human CD13 (IC50 = 0.13 µM) and the 20S proteasome (IC50 = 1.39 µM). Although BC-05 displayed lower anti-proliferative activity than that of ixazomib in vitro, an advantage was established in the in vivo anti-cancer efficacy and prolongation of survival time, which may be due to its anti-metastatic and immune-stimulating activity. A pharmacokinetic study revealed that BC-05 is a potentially orally active agent with an F% value of 24.9%. Moreover, BC-05 showed more favorable safety profiles than those of ixazomib in preliminary toxicity studies. Overall, the results indicate that BC-05 is a promising drug candidate for the treatment of multiple myeloma.

A preliminary study to explain how Streptomyces pactum (Act12) works on phytoextraction: soil heavy metal extraction, seed germination, and plant growth.

Streptomyces pactum (Act12) can both promote plant growth and strengthen heavy metal mobilization. Nevertheless, the mechanisms of how Act12 works during the phytoextraction process are still unknown. The present work investigated whether the metabolites produced by Act12 could influence the seed germination and the growth of potherb mustard and explored its mobilizing effect on soil cadmium (Cd) and zinc (Zn). The results showed that the germination potential and rate of potherb mustard seed treated with Act12 fermentation broth were 1.0- and 0.32-folds higher than those of control, probably due to the interruption of seed dormant stage. We also found that Act12 inoculation not only promoted the dry biomass (6.82%) of potherb mustard, but also increased the leaf chlorophyll (11.8%) and soluble protein (0.35%) production. The boosted seed germination rate under Act12 treatment (up to 63.3%) indicated that Act12 enhanced the resistance of potherb mustard seeds to Cd and Zn and alleviated their physiological toxicity. The generated metabolites during the Act12 fermentation posed positive impact on the availability of soil Cd and Zn. These findings bring new insight into the Act12-assisted phytoextraction of Cd and Zn from contaminated soils.

Rhizobacteria helps to explain the enhanced efficiency of phytoextraction strengthened by Streptomyces pactum.

The ultimate purpose of phytoextraction is not only to remove heavy metals from soil but also to improve soil quality. Here, we evaluated how the joint effect of Streptomyces pactum (strain Act12) and inorganic (Hoagland's solution) and organic (humic acid and peat) nutrients affected the phytoextraction practice of cadmium (Cd) and zinc (Zn) by potherb mustard, and the microbial community composition within rhizosphere was also investigated. The results indicated that the nutrients exerted synergistically with Act12, all increasing the plant biomass and Cd/Zn uptakes. The inoculation of Act12 alone significantly increased dehydrogenase activity of rhizosphere soil (P < 0.05), while urease and alkaline phosphatase activities varied in different dosage of Act12. Combined application of microbial strain with nutrients increased enzymatic activities with the elevated dosage of Act12. 16S ribosomal RNA high-throughput sequencing analysis revealed that Act12 inoculation reduced the diversity of rhizosphere bacteria. The Act12 and nutrients did not change dominant phyla i.e., Proteobacteria, Bacteroidetes, Gemmatimonadetes, Actinobacteria and Acidobacteria, but their relative abundance differed among the treatments with: Peat > Act12 > Humic acid > Hoagland's solution. Comparatively, Sphingomonas replaced Thiobacillus as dominant genus after Act12 application. The increase in the Sphingomonas and Flavisolibacter abundances under Act12 and nutrients treatments gave rise to growth-promoting effect on plant. Our results revealed the important role for rhizosphere microbiota in mediating soil biochemical traits and plant growth, and our approach charted a path toward the development of Act12 combined with soil nutrients to enhance soil quality and phytoextraction efficiency in Cd/Zn-contaminated soils.

The endocytosis of nano-Pt into non-small cell lung cancer H1299 cells and intravital therapeutic effect in vivo.

Lung cancer remains the most common fatal malignant disease, and the 5-year survival rate of patients with metastasis is merely 6%. In this research, the platinum nanocluster (short for nano-Pt) was used for optical imaging without the help of other fluorescent probes and possess targeted antitumor activity as well as low systemic toxicity. The endocytic pathway and distribution of nano-Pt in non-small cell lung cancer NSCLC H1299 cells was explored by the means of quantitative and qualitative tests. Furthermore, the targeting capability and antitumor efficiency of nano-Pt was detected by intravital imaging experiment and antitumor experiment. The research implies that nano-Pt entered H1299 cells dominatingly through macropinocytosis and clathrin-dependent endocytosis pathway, and has significant antitumor efficiency, targeting properties and reliable safety for mouse tumor, indicating this nano-Pt has great potential for clinical diagnosis and therapy of NSCLC H1299 cells.

Decavanadate Doped Polyaniline for Aqueous Zinc Batteries.

Polyaniline (PANI) is a promising cathode material for aqueous rechargeable zinc batteries (ARZBs), mainly benefitting from its good electrical conductivity. The high conductivity of PANI requires high doping level, yet the introduced nonactive dopants (e.g., SO4 2- ) limit the gravimetric capacity of PANI (usually < 180 mAh g-1 ). Herein, an electro-active dopant (decavanadate anion, V10 O28 6- ) is employed to fabricate the PANI cathode (PANI-V10 O28 ) for ARZBs. The doped decavanadate anion with the sub-nanometer structure can fully expose the V-based active sites, exhibiting good electrochemical activity. Due to the steric hindrance effect as well as the strong interaction between decavanadate anions and PANI chains, the active dopants are trapped in the polymer chains, demonstrating good structural and electrochemical stability. PANI-V10 O28 achieves a record-high gravimetric capacity of 355 mAh g-1 at 0.1 A g-1 , which is significantly higher than other reported PANI cathodes. Experimental results suggest that the charge storage mechanism of PANI-V10 O28 includes reversible injection/extraction of Zn(H2 O)2 Cl4 2- ions in PANI, as well as the protonation/deprotonation of V10 O28 6- . This work enriches the doping chemistry of conducting polymer and pushes the development of organic cathodes for ARZBs to a new stage.

The novel indomethacin derivative CZ-212-3 exerts antitumor effects on castration-resistant prostate cancer by degrading androgen receptor and its variants.

Androgen receptor (AR) serves as a main therapeutic target for prostate cancer (PCa). However, resistance to anti-androgen therapy (SAT) inevitably occurs. Indomethacin is a nonsteroidal anti-inflammatory drug that exhibits activity against prostate cancer. Recently, we designed and synthesized a series of new indomethacin derivatives (CZ compounds) via Pd (II)-catalyzed synthesis of substituted N-benzoylindole. In this study, we evaluated the antitumor effect of these novel indomethacin derivatives in castration-resistant prostate cancer (CRPC). Upon employing CCK-8 cell viability assays and colony formation assays, we found that these derivatives had high efficacy against CRPC tumor growth in vitro. Among these derivatives, CZ-212-3 exhibited the most potent efficacy against CRPC cell survival and on apoptosis induction. Mechanistically, CZ-212-3 significantly suppressed the expression of AR target gene networks by degrading AR and its variants. Consistently, CZ-212-3 significantly inhibited tumor growth in CRPC cell line-based xenograft and PDX models in vivo. Taken together, the data show that the indomethacin derivative CZ-212-3 significantly inhibited CRPC tumor growth by degrading AR and its variants and could be a promising agent for CRPC therapy.

p-n Junction Based Direct-Current Triboelectric Nanogenerator by Conjunction of Tribovoltaic Effect and Photovoltaic Effect.

Triboelectric nanogenerators (TENGs) have attracted much interest in recent years, due to its effectiveness and low cost for converting high-entropy mechanical energy into electric power. The traditional TENGs generate an alternating current, which requires a rectifier to provide a direct-current (DC) power supply. Herein, a dynamic p-n junction based direct-current triboelectric nanogenerator (DTENG) is demonstrated. When a p-Si wafer is sliding on a n-GaN wafer, carriers are generated at the interface and a DC current is produced along the direction of the built-in electric field, which is called the tribovoltatic effect. Simultaneously, an UV light is illuminated on the p-n junction to enhance the output. The results indicate that the current increases 13 times and the voltage increases 4 times under UV light (365 nm, 28 mW/cm2) irradiation. This work demonstrates the coupling between the tribovoltaic effect and the photovoltaic effect in DTENG semiconductors, promoting further development for energy harvesting in mechanical energy and photon energy.

A review on deep learning MRI reconstruction without fully sampled k-space.

BACKGROUND: Magnetic resonance imaging (MRI) is an effective auxiliary diagnostic method in clinical medicine, but it has always suffered from the problem of long acquisition time. Compressed sensing and parallel imaging are two common techniques to accelerate MRI reconstruction. Recently, deep learning provides a new direction for MRI, while most of them require a large number of data pairs for training. However, there are many scenarios where fully sampled k-space data cannot be obtained, which will seriously hinder the application of supervised learning. Therefore, deep learning without fully sampled data is indispensable. MAIN TEXT: In this review, we first introduce the forward model of MRI as a classic inverse problem, and briefly discuss the connection of traditional iterative methods to deep learning. Next, we will explain how to train reconstruction network without fully sampled data from the perspective of obtaining prior information. CONCLUSION: Although the reviewed methods are used for MRI reconstruction, they can also be extended to other areas where ground-truth is not available. Furthermore, we may anticipate that the combination of traditional methods and deep learning will produce better reconstruction results.