Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

[Effect of Xuming Decoction in Records of Proved Prescriptions, Ancient a nd Modern on cerebral ischemic injury and angiogenesis in rat model of acute cerebral infarction].

This paper aims to explore the effect of Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern on cerebral ischemic injury and angiogenesis in the rat model of acute cerebral infarction. SD rats were randomized into 6 groups: sham group, model group, low-, medium-, and high-dose(5.13, 10.26, and 20.52 g·kg~(-1), respectively) Xuming Decoction groups, and butylphthalide(0.06 g·kg~(-1)) group. After the successful establishment of the rat model by middle cerebral artery occlusion(MCAO), rats in the sham and model groups were administrated with distilled water and those in other groups with corresponding drugs for 7 consecutive days. After the neurological function was scored, all the rats were sacrificed, and the brain tissue samples were collected. The degree of cerebral ischemic injury was assessed by the neurological deficit score and staining with 2,3,5-triphenyltetrazolium chloride. Hematoxylin-eosin staining was performed to observe the pathological changes in the brain. Transmission electron microscopy was employed to observe the ultrastructures of neurons and microvascular endothelial cells(ECs) on the ischemic side of the brain tissue. Immunofluorescence assay was employed to detect the expression of von Willebrand factor(vWF) and hematopoietic progenitor cell antigen CD34(CD34) in the ischemic brain tissue. Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of Runt-related transcription factor 1(RUNX1), vascular endothelial growth factor(VEGF), angiopoietin-1(Ang-1), angiopoietin-2(Ang-2), and VEGF receptor 2(VEGFR2) in the ischemic brain tissue. The results showed that compared with the sham group, the model group showed increased neurological deficit score and cerebral infarction area(P<0.01), pathological changes, and damaged ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Furthermore, the modeling up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.05 or P<0.01). Compared with the model group, high-dose Xuming Decoction and butylphthalide decreased the neurological deficit score and cerebral infarction area(P<0.01) and alleviated the pathological changes and damage of the ultrastructure of neurons and microvascular ECs in the ischemic brain tissue. Moreover, they up-regulated the mRNA levels of RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01) and the protein levels of vWF, CD34, RUNX1, VEGF, Ang-1, Ang-2, and VEGFR2(P<0.01). The results suggest that Xuming Decoction in the Records of Proved Prescriptions, Ancient and Modern can promote the angiogenesis and collateral circulation establishment to alleviate neurological dysfunction of the ischemic brain tissue in MCAO rats by regulating the RUNX1/VEGF pathway.

High-throughput sequencing-based analysis of the composition and diversity of the endophyte community in roots of Stellera chamaejasme.

Stellera chamaejasme (S. chamaejasme) is an important medicinal plant with heat-clearing, detoxifying, swelling and anti-inflammatory effects. At the same time, it is also one of the iconic plants of natural grassland degradation in northwest China, playing a key role in the invasion process. Plant endophytes live in healthy plant tissues and can synthesize substances needed for plant growth, induce disease resistance in host plants, and enhance plant resistance to environmental stress. Therefore, studying the root endophytes of S. chamaejasme is of great significance for mining beneficial microbial resources and biological prevention and control of S. chamaejasme. This study used Illumina MiSeq high-throughput sequencing technology to analyze the composition and diversity of endophytes in the roots of S. chamaejasme in different alpine grasslands (BGC, NMC and XGYZ) in Tibet. Research results show that the main phylum of endophytic fungi in the roots of S. chamaejasme in different regions is Ascomycota, and the main phyla of endophytic bacteria are Actinobacteria, Proteobacteria and Firmicutes (Bacteroidota). Overall, the endophyte diversity of the NMC samples was significantly higher than that of the other two sample sites. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) results showed significant differences in the composition of endophytic bacterial and fungal communities among BGC, NMC and XGYZ samples. Co-occurrence network analysis of endophytes showed that there were positive correlations between fungi and some negative correlations between bacteria, and the co-occurrence network of bacteria was more complex than that of fungi. In short, this study provides a vital reference for further exploring and utilizing the endophyte resources of S. chamaejasme and an in-depth understanding of the ecological functions of S. chamaejasme endophytes.

Contribution of irreversible non-180° domain to performance for multiphase coexisted potassium sodium niobate ceramics.

Despite the dominance of lead-based piezoelectric materials with ultrahigh electric-field-induced strain in actuating applications, seeking eco-friendly substitutes with an equivalent performance remains an urgent demand. Here, a strategy of regulating the irreversible non-180° domain via phase engineering is introduced to optimize the available strain (the difference between the maximum strain and the remnant strain in a unipolar strain curve) in the lead-free potassium-sodium niobate-based piezoelectric ceramics. In situ synchrotron X-ray diffraction and Rayleigh analysis reveal the contribution of the non-180° domain to available strain in the tetragonal-orthorhombic-rhombohedral phase boundary. The reducing orthorhombic phase and increasing rhombohedral/tetragonal phase accompanied by the reduced irreversible non-180° domain are obtained with increasing doping of Sb5+, resulting in an enlarged available strain due to the significantly lowered remnant strain. This optimization is mainly attributed to the reduced irreversible non-180° domain wall motion and the increased lattice distortion, which are beneficial to decrease extrinsic contribution and enhance intrinsic contribution. The mesoscopic structure of miniaturized nanosized domain with facilitated domain switching also contributes to the enhancement of available strain due to the improved random field and decreased energy barrier. The study will shed light on the design of lead-free high-performance piezoelectric ceramics for actuator applications.

SPARC Stabilizes ApoE to Induce Cholesterol-Dependent Invasion and Sorafenib Resistance in Hepatocellular Carcinoma.

Dysregulation of cholesterol homeostasis is implicated in the development and progression of hepatocellular carcinoma (HCC) that is characterized by intrahepatic and early extrahepatic metastases. A better understanding of the underlying mechanisms regulating cholesterol metabolism in HCC could help identify strategies to circumvent the aggressive phenotype. Here, we found that high expression of intracellular SPARC (secreted protein acidic and rich in cysteine) was significantly associated with elevated cholesterol levels and an enhanced invasive phenotype in HCC. SPARC potentiated cholesterol accumulation in HCC cells during tumor progression by stabilizing the ApoE protein. Mechanistically, SPARC competitively bound to ApoE, impairing its interaction with the E3 ligase tripartite motif containing 21 (TRIM21) and preventing its ubiquitylation and subsequent degradation. ApoE accumulation led to cholesterol enrichment in HCC cells, stimulating PI3K-AKT signaling and inducing epithelial-mesenchymal transition (EMT). Importantly, sorafenib-resistant HCC cells were characterized by increased expression of intracellular SPARC, elevated cholesterol levels, and enhanced invasive capacity. Inhibiting SPARC expression or reducing cholesterol levels enhanced the sensitivity of HCC cells to sorafenib treatment. Together, these findings unveil interplay between SPARC and cholesterol homeostasis. Targeting SPARC-triggered cholesterol-dependent oncogenic signaling is a potential therapeutic strategy for advanced HCC. SIGNIFICANCE: Intracellular SPARC boosts cholesterol availability to fuel invasion and drug resistance in hepatocellular carcinoma, providing a rational approach to improve the treatment of advanced liver cancer.

Textured Potassium Sodium Niobate Lead-Free Ceramics with High d33 and Qm for Meeting High-Power Applications.

Potassium sodium niobate (KNN) lead-free piezoceramics have garnered significant attention for their environmentally friendly attributes, desired piezoelectric activity (d33), and high Curie temperature (Tc). However, the limited applicability of most KNN systems in high-power apparatus, including ultrasonic motors, transformers, and resonators, persists due to the inherent low mechanical quality factor (Qm). Herein, we proposed an innovative strategy for achieving high Qm accompanied by desirable d33 via synergistic chemical doping and texturing in KNN piezoceramics. Comprehensive electrical measurements along with quantitative structural characterization at multilength scales reveal that the excellent electromechanical properties (kp = 0.58, d33 ∼ 134 pC·N-1, Qm = 582, and Tc ∼ 415 °C) originate from the high <001> texturing degree, nanodomain, as well as acceptor hardening. Our findings provide an insight and guidance for achieving high-power performance in lead-free KNN-based piezoceramics, which were expected to be used in advanced transducer technology.

High-Throughput Screening of pH-Dependent ß-sheet Self-Assembling Peptide.

pH-dependent peptide biomaterials hold tremendous potential for cell delivery and tissue engineering. However, identification of responsive self-assembling sequences with specified secondary structure remains a challenge. In this work, An experimental procedure based on the one-bead one-compound (OBOC) combinatorial library is developed to rapidly screen self-assembling ß-sheet peptides at neutral aqueous solution (pH 7.5) and disassemble at weak acidic condition (pH 6.5). Using the hydrophobic fluorescent molecule thioflavin T (ThT) as a probe, resin beads displaying self-assembling peptides show fluorescence under pH 7.5 due to the insertion of ThT into the hydrophobic domain, and are further cultured in pH 6.5 solution. The beads with extinguished fluorescence are selected. Three heptapeptides are identified that can self-assemble into nanofibers or nanoparticles at pH 7.5 and disassemble at pH 6.5. P1 (LVEFRHY) shows a rapid acid response and morphology transformation with pH modulation. Changes in the charges of histidine and hydrophobic phenyl motif of phenylalanine may play important roles in the formation of pH-responsive ß-sheet nanofiber. This high-throughput screening method provides an efficient way to identify pH-dependent ß-sheet self-assembling peptide and gain insights into structural design of such nanomaterials.

Covalent drugs based on small molecules and peptides for disease theranostics.

Biomacromolecules, such as proteins, nucleic acids and polysaccharides, are widely distributed in the human body, and some of them have been recognized as the targets of drugs for disease theranostics. Drugs typically act on targets in two ways: non-covalent bond and covalent bond. Non-covalent bond-based drugs have some disadvantages, such as structural instability and environmental sensitivity. Covalent interactions between drugs and targets have a longer action time, higher affinity and controllability than non-covalent interactions of conventional drugs. With the development of artificial intelligence, covalent drugs have received more attention and have been developed rapidly in pharmaceutical research in recent years. From the perspective of covalent drugs, this review summarizes the design methods and the effects of covalent drugs. Finally, we discuss the application of covalent peptide drugs and expect to provide a new reference for cancer treatment.

Adventitious root culture of Lessertia frutescens for the production of triterpenoid saponins and polysaccharides.

Lessertia frutescens is a perennial shrub of commercial importance in South Africa, but the scarcity of plant resources has limited current product production. In this study, to provide an alternative approach for obtaining L. frutescens material, adventitious roots (ARs) were induced from sterilized seedlings and cultured in a suspension culture system. During this process, selection tests were conducted to find a suitable auxin and its concentration for AR induction and a suitable basal medium for AR growth and metabolite accumulation; a kinetic study was then performed to constructure kinetic models. The results showed that compared to other auxins and concentrations, indole-3-butyric acid at 3 mg/L was suitable for increasing the number and length of ARs during AR induction. In AR suspension culture, Schenk and Hildebrandt (SH) was better than other basal media, and the maximum AR fresh (86.9 g/L) or dry weight (5.5 g/L), total triterpenoid saponin (92.6 mg/g DW), and polysaccharide (114.7 mg/g DW) contents were determined in the 1.5×SH medium. In addition, AR biomass and metabolite contents reached the maximum on day 42. The kinetic models for AR growth and triterpenoid and polysaccharide production were constructed, providing the basis for further optimization of culture conditions and large-scale culture.

Bioorthogonal Engineered Virus-Like Nanoparticles for Efficient Gene Therapy.

Gene therapy offers potentially transformative strategies for major human diseases. However, one of the key challenges in gene therapy is developing an effective strategy that could deliver genes into the specific tissue. Here, we report a novel virus-like nanoparticle, the bioorthgonal engineered virus-like recombinant biosome (reBiosome), for efficient gene therapies of cancer and inflammatory diseases. The mutant virus-like biosome (mBiosome) is first prepared by site-specific codon mutation for displaying 4-azido-L-phenylalanine on vesicular stomatitis virus glycoprotein of eBiosome at a rational site, and the reBiosome is then prepared by clicking weak acid-responsive hydrophilic polymer onto the mBiosome via bioorthogonal chemistry. The results show that the reBiosome exhibits reduced virus-like immunogenicity, prolonged blood circulation time and enhanced gene delivery efficiency to weakly acidic foci (like tumor and arthritic tissue). Furthermore, reBiosome demonstrates robust therapeutic efficacy in breast cancer and arthritis by delivering gene editing and silencing systems, respectively. In conclusion, this study develops a universal, safe and efficient platform for gene therapies for cancer and inflammatory diseases.

A facile spray-pressing synthesis approach for reusable photothermal masks.

Certain types of face masks are highly efficient in protecting humans from bacterial and viral pathogens, and growing concerns with high safety, low cost, and wide market suitability have accelerated the replacement of reusable face masks with disposable ones during the last decades. However, wearing these masks creates countless problems associated with personnel comfort as well as more significant issues related to the cost of fabrication, the generation of medical waste, and environmental contaminants. In this work, we present a facile spray-pressing technique for the production of P-masks with a potential scale-up prospect by adding a graphene layer on one side of meltblown fabric and a functional layer on the other side. In principle, this technique could be easily integrated into the present automatic mask production process and the masks have self-cleaning and/or self-sterilizing properties when it is exposed to solar or simulated solar irradiation.

Entangling of Peptide Nanofibers Reduces the Invasiveness of SARS-CoV-2.

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.

[CiteSpace knowledge map of gut microbiota research involving traditional Chinese medicine in recent twenty years].

We employed bibliometrics to comprehensively study the hotspots and frontiers of gut microbiota research involving traditional Chinese medicine(TCM), aiming to provide new ideas for the subsequent research in this field. The studies of gut microbiota with TCM published from January 1, 2002 to December 31, 2021 were retrieved from CNKI, Wanfang, VIP and Web of Science(WoS). After data screening and cleaning, CiteSpace 5.8.R3 was used to visualize and analyze the authors, journals, and keywords. A total of 1 119 Chinese articles and 815 English articles were included in the study. The period of 2019-2021 witnessed the surge in the number of articles published in this field, being the peak research period. TAN Zhou-jin and DUAN Jin-ao were the authors publishing the most articles in Chinese and English, respectively. The two authors ranked top in both Chinese and English articles, playing a central role in this research field. The top five Chinese and English journals in this field had a large influence in the international research field. High-frequency keywords and keyword clustering showed that the research hotspots in this field were concentrated in four areas: trial and clinical research on the regulation of gut microbiota in disease treatment by TCM, metabolic transformation of Chinese medicines by gut microbiota, and the effect of TCM added to feed on the gut microbiota and growth performance of animals. The study of gut microbiota structure in patients with different TCM syndromes, as well as that of TCM combined with probiotics/flora transplantation in the treatment of diseases, can provide new ideas for clinical diagnosis and traditional drug treatment of diseases and has great research space and research value in the future.

Advances in Cancer Nanovaccines: Harnessing Nanotechnology for Broadening Cancer Immune Response.

Many advances have been made recently in the field of cancer immunotherapy, particularly with the development of treatments such as immune checkpoint inhibitors and adoptive cellular immunotherapy. The efficacy of immunotherapy is limited, however, owing to high levels of tumor heterogeneity and the immunosuppressive environments of advanced malignant tumors. Therefore, therapeutic anticancer vaccines have gradually become powerful tools for inducing valid antitumor immune responses and regulating the immune microenvironment. Tumor vaccines loaded in nanocarriers have become an indispensable delivery platform for tumor treatment because of their enhanced stability, targeting capability, and high level of safety. Through a unique design, cancer nanovaccines activate innate immunity and tumor-specific immunity simultaneously. For example, the design of cancer vaccines can incorporate strategies such as enhancing the stability and targeting of tumor antigens, combining effective adjuvants, cytokines, and immune microenvironment regulators, and promoting the maturation and cross-presentation of antigen-presenting cells (APCs). In this review, we discuss the design and preparation of nanovaccines for remodeling tumor antigen immunogenicity and regulating the immunosuppressive microenvironment.

1T-MoS2 Enriched Hierarchical MoS2 /MoO3 Produced by Phase Transformation for Efficient Hydrogen Evolution Reaction.

In recent years, transition metal sulfides have been widely studied in the context of their use as electrocatalysts. The electrocatalytic propensity of the classical semiconductor MoS2 , which exists in the 1T and 2H phase structures, has attracted extensive attention. Therefore, the synthesis of highly active and stable MoS2 -based catalysts has become the goal of many research efforts. We recently developed a method that can be utilized to prepare the MoS2 /MoO3 heterojunction in a phase-controlled manner. 1T-MoS2 phase enriched MoS2 /MoO3 heterojunction can be generated using a simple hydrothermal and acid treatment sequence and that the heterojunction has a unique three-dimensional structure, large active surface area, and therefore achieve a low overpotential and high catalytic current density, as well as long-term stability for the hydrogen evolution reaction.

Identifying the Interfacial Polarization in Non-stoichiometric Lead-Free Perovskites by Defect Engineering.

Recent advances in perovskite ferroelectrics have fostered a host of exciting sensors and actuators. Defect engineering provides critical control of the performance of ferroelectric materials, especially lead-free ones. However, it remains a challenge to quantitatively study the concentration of defects due to the complexity of measurement techniques. Here, a feasible approach to analyzing the A-site defect and electron in alkali metal niobate is demonstrated. The theoretical relationships among defect concentration, conductivity, and oxygen partial pressure can be established based on the defect chemistry equilibria. The type and concentration of defects are reflected through the conductivity variation with oxygen partial pressure. As a result, the variation of defect concentration gives rise to defect-driven interfacial polarization, which further leads to distinct properties of the ceramics. e.g., abnormal dielectric behavior. Furthermore, this study also suggests a strategy to manipulate defects and charges in perovskite oxides for performance optimization.

Posttraumatic growth in children aged 8-18 years with malignancies in China.

OBJECTIVE: To establish a nomogram prediction model for posttraumatic growth (PTG) in children aged 8-18 years with malignancies in China and to convenient intuitively judge psychological tendencies. METHODS: We recruited 358 children aged 8-18 years with malignancies in China as the study participants. Data from 250 cases collected from June 2019 to November 2019 were used as the model group, data from 108 cases collected from December 2019 to January 2020 were used as the validation group. Logistic regression was used to analyze the influencing factors of PTG in the model group. A prediction model was then established using a nomogram. The centrality measurement index(C-index) and receiver operating characteristic curves (ROC) were used to verify the model. RESULTS: Among the 250 children in the model group, 65 children with malignancies had PTG, with an occurrence of 26%. The model showed that the child's age, diagnosis, coping style and self-efficacy level and the educational level of the caregiver were core predictors of PTG (P < 0.05). The ROC of the model was 0.837, the best cutoff value was 0.566. The C-indexes of the internal and external validation were 0.837 (95% CI: 0786 ~ 0.886) and 0.813 (95% CI: 0732 ~ 0.894), respectively. CONCLUSIONS: The prediction model of PTG in children aged 8-18 years with malignancies in China has good discrimination and consistency and can accurately predict PTG. It can be used to clinically assess the psychological status of children in the future.

CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription.

Epigenetic alterations have been functionally linked to ovarian cancer development and occurrence. The CXXC zinc finger protein 1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. However, its role in ovarian cancer cells is unknown. Here, we show that CFP1 protein is highly expressed in human ovarian cancer tissues. Loss of CFP1 inhibited the growth of human ovarian cancer cells, promoted apoptosis, and increased senescence. CFP1 knockdown resulted in reduced levels of SETD1 (a CFP1 partner) and histone H3 trimethylation at the fourth lysine residue (H3K4me3). RNA-sequencing revealed that deletion of CFP1 resulted in mRNA reduction of bone marrow stromal cell antigen 2 (BST2). Bioinformatics analysis and chromatin immunoprecipitation showed that CFP1 binds to the promoter of BST2 and regulates its transcription directly. Overexpression of BST2 rescued the growth inhibitory effect of CFP1 loss. Furthermore, depletion of cullin-RING ubiquitin ligases 4 (CRL4) components ROC1 or CUL4A had significantly inhibited the expression of CFP1 and BST2 similar to MLN4924 treatment that blocked cullin neddylation and inactivated CRL4s. In conclusion, CFP1 promotes ovarian cancer cell proliferation and apoptosis by regulating the transcription of BST2, and the expression of CFP1 was affected by CRL4 ubiquitin ligase complex.

Metabolomic Analysis Uncovers Lipid and Amino Acid Metabolism Disturbance During the Development of Ascites in Alcoholic Liver Disease.

Ascites is one of the most common complications of cirrhosis, and there is a dearth of knowledge about ascites-related pathologic metabolism. In this study, 122 alcoholic liver disease (ALD) patients, including 49 cases without ascites, 18 cases with mild-ascites, and 55 cases with large-ascites (1) were established according to the International Ascites Club (2), and untargeted metabolomics coupled with pattern recognition approaches were performed to profile and extract metabolite signatures. A total of 553 metabolites were uniquely discovered in patients with ascites, of which 136 metabolites had been annotated in the human metabolome database. Principal component analysis (PCA) analysis was used to further identify 21 ascites-related fingerprints. The eigenmetabolite calculated by reducing the dimensions of the 21 metabolites could be used to effectively identify those ALD patients with or without ascites. The eigenmetabolite showed a decreasing trend during ascites production and accumulation and was negatively related to the disease progress. These metabolic fingerprints mainly belong to the metabolites in lipid metabolism and the amino acid pathway. The results imply that lipid and amino acid metabolism disturbance may play a critical role in the development of ascites in ALD patients and could be a potent prognosis marker.