Polygonum cuspidatum polysaccharide: A review of its extraction and purification, structure analysis, and biological activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum cuspidatum Sieb. et Zucc. is mainly distributed in Shanxi, Gansu, and Sichuan province of China. It is also found in Korea and Japan. Its dried roots and rhizomes are used as medicinal herbs and have been used to treat hyperglycemia and various inflammatory disorders. AIM OF THE REVIEW: This paper aims to provide an up-to-date review of the developments in the studies involving the extraction and purification, structure analysis, pharmacological effects, and potential applications of polysaccharides obtained from Polygonum cuspidatum. Additionally, the possible future research directions of this plant are discussed. MATERIALS AND METHODS: This article used "Polygonum cuspidatum polysaccharide (PCP)" and "Polygonum cuspidatum" as the keywords and gathered relevant data on Polygonum cuspidatum using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb. RESULTS: Excluding irrelevant and repetitive documents, 278 documents were finally included, of which 88 were in Chinese and 190 were in English. The CiteSpace software was used to visualize the trends and keywords in this research field. We concluded that the main extraction methods for Polygonum cuspidatum polysaccharide are water extraction and alcohol precipitation, microwave-assisted extraction, ultrasound-assisted extraction, and microjet extraction. High-performance liquid chromatography and column chromatography are also commonly used in the separation and purification of PCP. PCP has antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. This paper provides an updated and deeper understanding of PCP, serving as a theoretical foundation for the further optimization of polysaccharide structures and the development of PCP as a novel functional material for clinical application.

Spatial-temporal characteristics and driving factors' contribution and evolution of agricultural non-CO2 greenhouse gas emissions in China: 1995-2021.

Comprehending the spatial-temporal characteristics, contributions, and evolution of driving factors in agricultural non-CO2 greenhouse gas (GHG) emissions at a macro level is pivotal in pursuing temperature control objectives and achieving China's strategic goals related to carbon peak and carbon neutrality. This study employs the Intergovernmental Panel on Climate Change (IPCC) carbon emissions coefficient method to comprehensively evaluate agricultural non-CO2 GHG emissions at the provincial level. Subsequently, the contributions and spatial-temporal evolution of six driving factors derived from the Kaya identity were quantitatively explored using the Logarithmic Mean Divisia Index (LMDI) and Geographical and Temporal Weighted Regression (GTWR) methods. The results revealed that the distribution of agricultural non-CO2 GHG emissions is shifting from the central provinces to the northwest regions. Moreover, the dominant driving factors of agricultural non-CO2 GHG emissions were primarily economic factor (EDL) with positive impact (cumulative promotion is 2939.61 million metric tons (Mt)), alongside agricultural production efficiency factor (EI) with negative impact (cumulative reduction is 2208.98 Mt). Influence of EDL diminished in the eastern coastal regions but significantly impacted underdeveloped regions such as the northwest and southwest. In the eastern coastal regions, EI gradually became the absolute dominant driver, demonstrating a rapid reduction effect. Additionally, a declining birth rate and rural-to-urban population migration have significantly amplified the driving effects of the population factor (RP) at a national scale. These findings, in conjunction with the disparities in geographic and socioeconomic development among provinces, can serve as a guiding framework for the development of a region-specific roadmap aimed at reducing agricultural non-CO2 GHG emissions.

The effect of the mitochondria-targeted antioxidant Mito-tempo during sperm ultra-rapid freezing.

During the freeze-thaw process, human spermatozoa are susceptible to oxidative stress, which may cause cryodamage and reduce sperm quality. As a novel mitochondria-targeted antioxidant, Mito-tempo has been used for sperm cryopreservation. However, it is currently unknown what role it will play in the process of sperm ultra-rapid freezing. The purpose of this study was to investigate whether Mito-tempo can improve sperm quality during ultra-rapid freezing. In this study, samples with the addition of Mito-tempo (0, 5, 10, 20, and 40 µM) to sperm freezing medium were selected to evaluate the changes in sperm quality, antioxidant capacity and ultrastructure after ultra-rapid freezing. After ultra-rapid freezing, the quality and antioxidant function of the spermatozoa were significantly reduced and the spermatozoa ultrastructure was destroyed. The addition of 10 µM Mito-tempo significantly increased post thaw sperm motility, viability, plasma membrane integrity and mitochondrial membrane potential (P < 0.05). Moreover, the DNA fragmentation index (DFI), ROS levels and MDA content were reduced, and the antioxidant enzyme (CAT and SOD) activities were enhanced in the 10 µM Mito-tempo group (P < 0.05). Moreover, Mito-tempo protected sperm ultrastructure from damage. In conclusion, Mito-tempo improved the quality and antioxidant function of sperm after ultra-rapid freezing while reducing freezing-induced ultrastructural damage.

Relative quantitation of chiral thiol compounds labeled based on isotope novel mass spectrometry probes: Monitoring of the dynamic changes of chiral thiol compounds in human urine during normal, exercise, and rest recovery states.

Monitoring changes in the content of chiral thiol compounds in the human body is crucial for the early diagnosis of oxidative stress-related diseases and the exploration of their pathogenesis. To address this, we synthesized a novel isotope mass spectrometry (MS) probe, denoted as (R)-(5-(3-isothiocyanato (13C) pyrrolidin-1-yl)-5-oxopentyl) triphenylphosphonium (N13CS-OTPP), with triphenylphosphine as its parent structure. In this study, we established a new ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLCHRMS) relative quantitative method to monitor chiral thiol compounds in human urine under varying oxidative stress conditions. This method relies on the ratio of 12C/13C isotope-labeled peak areas. To assess the chiral separation efficiency of N13CS-OTPP, we employed three types of thiol compounds (D/L-GSH, D/L-Cys, and D/L-Hcy) and observed separation degrees (Rs) ranging from 1.82 to 1.89. We further validated the accuracy and feasibility of our relative quantitative methods using D/L-Cys-as a model compound. N12C/13CS-OTPP-Cys-exhibited excellent linearity (R2 = 0.9993-0.9994) across different molar ratios (D/L-Cys = 10:1, 4:1, 2:1, 1:1, 1:2, 1:4, 1:10) and achieved a low limit of detection (LOD) of 2.5 fmol. Additionally, we monitored the dynamic changes in urine D/L-Cys-and D/L-Hcy ratios in 12 healthy volunteers (six males and six females) under various oxidative stress states. We generated fitting curves and investigated the trends in chiral thiol compounds in vivo. This study introduces a novel method for the relative quantitative monitoring of chiral thiol compounds in different oxidative stress states within the human body. It also presents a new strategy for understanding the pathogenesis of related diseases resulting from the abnormal metabolism of thiol compounds.

Homodimeric peptide radiotracer [68Ga]Ga-NOTA-(TMVP1)2 for VEGFR-3 imaging of cervical cancer patients.

PURPOSE: Vascular endothelial growth factor receptor 3 (VEGFR-3) plays a critical role in tumor lymphangiogenesis and metastasis, holding promise as a promising therapeutic target for solid tumors. TMVP1 (LARGR) is a 5-amino acid peptide previously identified in our laboratory from bacterial peptide display system that specifically targets VEGFR-3. Radiolabeled TMVP1 can be used for non-invasive imaging of VEGFR-3 expressing tumors. Homodimeric peptides have better targeting ability than monomeric peptides, and it is worth exploring whether homodimers of TMVP1 ((TMVP1)2) can achieve better imaging effects. This study aimed to explore the peptide properties and tumor assessment value of [68Ga]Ga-labeled (TMVP1)2. METHODS: In this study, we developed a TMVP1 homodimer that was conjugated with 1,4,7-triazacyclononane-N, N', N″-triacetic acid (NOTA) via tetraethyleneglycol (PEG4) and triglyicine (Gly3) spacer, and labeled with 68Ga, to construct [68Ga]Ga-NOTA-(TMVP1)2. Binding of VEGFR-3 by TMVP1 and (TMVP1)2, respectively, was modeled by molecular docking. The affinity of [68Ga]Ga-NOTA-(TMVP1)2 for VEGFR-3 and its ability to bind to cells were evaluated. MicroPET imaging and biodistribution studies of [68Ga]Ga-NOTA-(TMVP1)2 were performed in subcutaneous C33A cervical cancer xenografts. Five healthy volunteers and eight patients with cervical cancer underwent whole-body PET/CT acquisition 30-45 min after intravenous injection of [68Ga]Ga-NOTA-(TMVP1)2. RESULTS: Both molecular docking and cellular experiments showed that homodimeric TMVP1 had a higher affinity for VEGFR-3 than monomeric TMVP1. [68Ga]Ga-NOTA-(TMVP1)2 was excreted mainly through the renal route and partly through the liver route. In mice bearing C33A xenografts, [68Ga]Ga-NOTA-(TMVP1)2 specifically localized in the tumor (2.32 ± 0.10% ID/g). Pretreatment of C33A xenograft mice with the unlabeled peptide NOTA-(TMVP1)2 reduced the enrichment of [68Ga]Ga-NOTA-(TMVP1)2 in tumors (0.58 ± 0.01% ID/g). [68Ga]Ga-NOTA-(TMVP1)2 proved to be safe in all healthy volunteers and recruited patients, with no side effects or allergies noted. In cervical cancer patients, a majority of the [18F]-FDG identified lesions (18/22, 81.8%) showed moderate to high signal intensity on [68Ga]Ga-NOTA-(TMVP1)2. SUVmax and SUVmean were 2.32 ± 0.77 and 1.61 ± 0.48, respectively. With normal muscle (gluteus maximus) as background, tumor-to-background ratios were 3.49 ± 1.32 and 3.95 ± 1.64 based on SUVmax and SUVmean, respectively. CONCLUSION: The favorable characterizations of [68Ga]Ga-NOTA-(TMVP1)2 such as convenient synthesis, high specific activity, and high tumor uptake enable the evaluation of VEGFR-3 in cervical cancer patients and warrant further clinical studies. TRIAL REGISTRATION: ChiCTR-DOD-17012458. Registered August 23, 2017 (retrospectively registered).

Integrated physical and mental management for China's elderly: insights from Long-gang District, Shenzhen.

China is in a period of rapid population aging. The total population of the elderly aged 60 and above in mainland China was 264 million in 2020, and is the country with the largest elderly population in the world, which is home to 1/5 of the world's older people. The urgency of actively coping with the aging population has never been greater, and China has raised it to the height of national strategy. To this end, China has issued several plans and projects on aging work. Many of them include multiple overlapping components. The management of physical illness and mental illness in the elderly is over-differentiated and segmented. However, it is common for older adults with complex health problems. The body and mind are inherently integrated and interact with each other, and should not be separated. There is an urgent need for integrated healthcare services for the physical and mental health of the elderly population. The national basic public health services play an important role in early detection and awareness of health problems for the elderly in community health services. This paper introduces the elderly health management services, one of the national basic public health projects, and the psychological care project for the elderly in Shenzhen, Guangdong Province, China. Taking Long-gang District's exploration of the joint management of physical and mental health of the elderly as an example, this review discusses the difficulties of the elderly health work, and the feasibility of integrating the elderly mental health and physical health in medical care. We outlook to build an integrated platform for physical and mental health of the elderly in China. Focus on the needs of older population, strengthen community health services, build a integrative team, fully publicize and improve health literacy of the elderly, link up and down and work together, improve coordination between providers of medical care and social services. It is of great significance to construct a strong public health system for the elderly and promote the realization of the grand goal of Healthy China.

Integrative Analysis of miRNA and circRNA Expression Profiles and Interaction Network in HSV-1-Infected Primary Corneal Epithelial Cells.

PURPOSE: Circular RNAs (circRNAs) are products of alternative splicing with roles as competitive endogenous RNAs or microRNA sponges, regulating gene expression and biological processes. However, the involvement of circRNAs in herpes simplex keratitis remains largely unexplored. METHODS: This study examines circRNA and miRNA expression profiles in primary human corneal epithelial cells infected with HSV-1, compared to uninfected controls, using microarray analysis. Bioinformatic analysis predicted the potential function of the dysregulated circRNAs and microRNA response elements (MREs) in these circRNAs, forming an interaction network between dysregulated circRNAs and miRNAs. RESULTS: A total of 332 circRNAs and 16 miRNAs were upregulated, while 80 circRNAs and six miRNAs were downregulated (fold change ≥2.0 and p < 0.05). Gene ontology (GO) and KEGG pathway analyses were performed on parental genes of dysregulated circRNAs to uncover potential functions in HSV-1 infection. Notably, miR-181b-5p, miR-338-3p, miR-635, and miR-222-3p emerged as pivotal miRNAs interacting with multiple dysregulated circRNAs. CONCLUSIONS: This comprehensive study offers insights into differentially expressed circRNAs and miRNAs during HSV-1 infection in corneal epithelial cells, shedding light on circRNA-miRNA interactions' potential role in herpes simplex keratitis pathogenesis.

Effect of Sonic hedgehog gene-modified bone marrow mesenchymal stem cells on graft-induced retinal gliosis and retinal ganglion cells survival in diabetic mice.

AIM: To investigate the effects of Sonic hedgehog (Shh) gene-modified bone marrow mesenchymal stem cells (MSCs) on graft-induced retinal gliosis and retinal ganglion cells (RGCs) survival in diabetic mice. METHODS: Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs (MSC-Shh). Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs (MSC-Gfp; control) were administered in diabetic mice. After 4wk, the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography, and markers of gliosis were examined by immunofluorescence and Western blotting. The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence. The mechanisms underlying the effects of MSC-Shh was investigated. RESULTS: A significant reduction of proliferative vitreoretinopathy (PVR) was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp. Significant downregulation of glial fibrillary acidic protein (GFAP) was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp. The extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (AKT) and phosphatidylin-ositol-3-kinase (PI3K) pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) levels were significantly increased in the host retina, and RGCs loss was significantly prevented after MSC-Shh administration. CONCLUSION: MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice. The ERK1/2, AKT and PI3K pathways are involved in this process. MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.

Causal effect of age first had sexual intercourse and lifetime number of sexual partners on cervical cancer.

Objective: In this study, we aimed to investigate whether age first had sexual intercourse (AFSI) and lifetime number of sexual partners (LNSP) have a direct causal effect on cervical cancer by Mendelian randomization (MR) analysis. Methods: Four approaches were used for MR Analysis, including MR-Egger, weighted method, weighted median, and inverse variance weighted (IVW). MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) as well as MR-Egger regression analysis were conducted to detect whether there was pleiotropy between IVs and outcome, and the outlier SNPs can be detected by MR-PRESSO. The presence or absence of heterogeneity among IVs was suggested according to Cochran's Q statistic. Leave-one-out sensitivity analysis was performed to identify and remove SNPs which could independently change the results. We corrected the results using Bonferroni correction. Results: From the results of IVW, AFSI had a negative effect on cervical cancer (OR = 0.996, 95 % CI: 0.995, 0.998 P = 1.70E-07), which still persisted after Bonferroni correction. However, no causal effect of LNSP on cervical cancer was found according to the IVW results (OR = 1.003, 95 % CI: 1.000, 1.007, P = 0.071). From the results of MR-PRESSO and MR-Egger, no SNP with horizontal pleiotropy between cervical cancer was detected and no SNP was identified as an outlier SNP. Cochran's Q statistic suggested that no heterogeneity existed among IVs of AFSI and LNSP. According to Leave-one-out analysis, the results of MR did not change after excluding any single IV. Conclusion: This MR study reveals that early AFSI has a causal effect on cervical cancer.

Simultaneous analysis of natural and artificial sweeteners in sugar-free drinks and urine samples by column-switching UHPLC-charged aerosol detection method.

Sweeteners are considered an alternative to high-calorie foods or drinks and have been widely used globally. However, the simultaneous separation and detection of high-polarity natural and artificial sweeteners are challenging owing to their broad-spectrum physical and chemical properties. Herein, we developed a column-switching UHPLCCAD method and used it for detecting and quantitating 12 sweeteners, including natural sweeteners (erythritol, mannitol, xylitol, sorbitol and stevioside) and artificial sweeteners (acesulfame potassium, saccharin sodium salt, sodium cyclamate, sucralose, aspartame, alitame and neotame). The LOD and LOQ were 0.932-6.25 µg/mL and 3.10-20.83 µg/mL, respectively, and the method demonstrated excellent linearity (R² ≥ 0.9990), good precision (intraday and interday precision was 0.59-6.88 %), and high recovery (average recoveries were 85.16-108.64 %). This method was applied to determine the sweeteners in 15 sugar-free drinks purchased from the local Chinese supermarkets. What's more, natural sweetener erythritol and artificial sweetener acesulfame potassium were suspected over addition in sugar-free drinks. Meanwhile the method was applied to the sweeteners in various sugar-free drinks and the dynamic monitoring of transit and excretion in vivo after drinking. Those prove that the method can be used to the detection of sugar free drinks and quality control of the sweeteners. The study highlights the potential of UHPLC-charged aerosol detection technology in detection of multiple components in food industry.

A comparison of psychiatric symptoms between mental health professionals with and without post-infection sequelae of COVID-19.

Post-infection sequelae of COVID-19 (PISC) have raised public health concerns. However, it is not clear whether infected mental health professionals (MHPs) with PISC have experienced more psychiatric symptoms than MHPs without PISC do. This study examined differences in the prevalence of self-reported depression, anxiety, insomnia and suicidality as well as the network structures of these symptoms between these two groups. Participants completed questionnaire measures of psychiatric symptoms and demographics. Expected influence was used to measure centrality of symptoms and network comparison tests were adopted to compare differences in the two network models. The sample comprised 2,596 participants without PISC and 2,573 matched participants with PISC. MHPs with PISC had comparatively higher symptom levels related to depression (55.2% vs. 23.5 %), anxiety (32.0% vs. 14.9 %), insomnia (43.3% vs. 17.3 %), and suicidality (9.6% vs. 5.3 %). PHQ4 ("Fatigue"), PHQ6 ("Guilt"), and GAD2 ("Uncontrollable Worrying") were the most central symptoms in the "without PISC" network model. Conversely, GAD3 ("Worry too much"), GAD5 ("Restlessness"), and GAD4 ("Trouble relaxing") were more central in the "with PISC" network model. In sum, MHPs with PISC experienced comparatively more psychiatric symptoms and related disturbances. Network results provide foundations for the expectation that MHPs with PISC may benefit from interventions that address anxiety-related symptoms, while those without PISC may benefit from interventions targeting depression-related symptoms.

Unusually High-Spin Fe12C12- Metallo-Carbohedrene Clusters.

Ferromagnets constructed from nanometals of atomic precision are important for innovative advances in information storage, energy conversion, and spintronic microdevices. Considerable success has been achieved in designing molecular magnets, which, however, are challenging in preparation and may suffer from drawbacks on the incompatibility of high stability and strong ferromagnetism. Utilizing a state-of-the-art self-developed mass spectrometer and a homemade laser vaporization source, we have achieved a highly efficient preparation of pure iron clusters, and here, we report the finding of a strongly ferromagnetic metal-carbon cluster, Fe12C12-, simply by reacting the Fen- clusters with acetylene in proper conditions. The unique stability of this ferromagnetic Fe12C12- cluster is rooted in a plumb-bob structure pertaining to Jahn-Teller distortion. We classify Fe12C12- as a new member of metallo-carbohedrenes and elucidate its structural stability mechanism as well as its soft-landing deposition and magnetization measurements, providing promise for the exploration of potential applications.

Ecological drought monitoring of Inner Mongolia vegetation growing season based on kernel temperature vegetation drought index (kTVDI).

Ecological drought monitoring is important for regional status assessment and protection of water resources. In this study, we constructed a new ecological drought index, the kernel temperature vegetation drought index (kTVDI), by using the kernel normalized vegetation index (kNDVI) to improve the temperature vegetation drought index (TVDI) in Inner Mongolia. We further analyzed the spatial and temporal distribution of ecological drought in Inner Mongolia during 2000-2022 and the future trend of ecological drought by using segmented linear regression model, Theil-Sen median, Mann-Kendall test, and Hurst index. The results showed that kTVDI performed better in monitoring ecological drought than TVDI. From 2000 to 2022, kTVDI showed a decreasing trend in the growing season in Inner Mongolia, but the change was not significant, and a sudden change occurred in 2016, and the wetting trend after the sudden change was more obvious. During the study period, ecological drought in 23.6% of the areas of Inner Mongolia showed an aggravating trend, and ecological drought was alleviated in 46.5% of the area. In the future, ecological drought would be exacerbated in the eastern part but alleviated in the central and western parts of Inner Mongolia.

Cross-Platform Application of DNA Methylation Age Estimation Model in Eastern Chinese Han Population.

OBJECTIVES: To evaluate the forensic application value of an age estimation model based on DNA methylation in eastern Chinese Han population, and to provide a theoretical basis for exploring age estimation models suitable for different detection platforms. METHODS: According to the 6 age-related methylation sites in the published blood DNA methylation age estimation models of Chinese Han population, the DNA methylation level of 48 samples was detected by pyrosequencing and next-generation sequencing (NGS). After submitting DNA methylation levels to the age estimation model, the DNA methylation ages were predicted and compared with their real ages. RESULTS: The 6 DNA methylation sites in both detection techniques were age-related, with an R2 of 0.85 and a median absolute deviation (MAD) of 4.81 years when using pyrosequencing；with an R2 of 0.84 and MAD of 4.41 years when using NGS. CONCLUSIONS: The blood DNA methylation age estimation model can be used under pyrosequencing and multi-purpose regional methylation enrichment sequencing technology based on NGS and it can accurately estimate the age.

Anion Photoelectron Spectroscopy and Theoretical Studies of Ge3n+1O (n = 1-3) Clusters with the C3v Symmetric Ge3 Structural Unit.

We investigate Ge3n+1O-/0 (n = 1-3) clusters using anion photoelectron spectroscopy and theoretical calculations. The results show that the lowest energy structure of Ge4O- is a bent Cs symmetric trigonal bipyramidal structure, while Ge4O has a C3v symmetric trigonal bipyramidal structure. Ge7O- has two coexisting low-lying isomers, the first one can be viewed as a Ge2O unit interacting with a Ge5 trigonal bipyramid, the second one can be regarded as an O atom interacting with a Ge7 pentagonal bipyramid; whereas Ge7O has a C3v symmetric structure with a Ge atom and an O atom capping a Ge6 trigonal antiprism from the bottom and top, respectively. The structures of Ge10O- and Ge10O can be obtained by adding an O atom to different binding sites of a C3v symmetric Ge10. Chemical bonding analyses of Ge3n+1O (n = 1-3) reveal that the O atom interacts with its neighboring three Ge atoms forming one 4c-2e σ bond and two 4c-2e π bonds in the top Ge3O trigonal pyramid, while the terminal Ge atom forms one 4c-2e σ bond in the bottom Ge4 trigonal pyramid. The large HOMO-LUMO gaps of Ge3n+1O (n = 1-3) indicate that they have good stabilities. Ab initio molecular dynamics simulations suggest that both Ge7O and Ge10O are dynamically stable in general at 300 and 500 K. The current work suggests that the C3v symmetric Ge3 units and the insertion growth pattern may be viable for constructing 1D germanium oxide nanostructures with the chemical formula of Ge3n+1O.

Diarylpentanoids and phenylpropanoids from the roots of Anthriscus sylvestris (L.) Hoffm.

Three pairs of undescribed diarylpentanoid enantiomers (1-3) and five undescribed phenylpropanoids (4-8), along with seven known compounds, were isolated from the roots of Anthriscus sylvestris. The structures of compounds (1-8) were determined by analysis of their 1D and 2D NMR spectra, HRESIMS, and electronic circular dichroism. In addition, the inhibitory activities against hypoxia-stimulated pulmonary arterial smooth muscle cells abnormal proliferation were evaluated by MTT assay. The mRNA expression levels of Bcl-2, BAX, Caspase3, and IL-6 were detected by quantitative real-time PCR. The results showed that compounds (-)-1, (+)-1, (-)-2, (+)-3, 4, 8-10, 14, and 15 inhibited the abnormal proliferation of PASMCs by regulating the levels of apoptosis and inflammatory factors.

Structures and Properties of Planar Ge3O3 Cluster and Its Buckled Honeycomb Two-Dimensional Nanostructure.

The discovery of graphene and its excellent properties inspired the search for more two-dimensional (2D) materials. Understanding the structures and properties of the smallest repeating units as well as crystal 2D materials is helpful for designing 2D materials. As germanium tends to form three-dimensional structures, the preparation of germanium-based 2D nanomaterials is still a challenge. Herein, we report a Ge3O3 cluster with the potential to construct a germanium oxide 2D nanostructure. We conduct a combined anion photoelectron spectroscopy and theoretical study on Ge3O3-/0. The structure of Ge3O3- is a Cs symmetric nonplanar six-membered ring, while that of Ge3O3 is a D3h symmetric planar six-membered ring. Chemical bonding analyses reveal that Ge3O3 exhibits π aromaticity. First-principle results suggest that a buckled honeycomb 2D nanostructure with a wide band gap of 3.14 eV may be produced based on Ge3O3, which is promising in optoelectronic applications especially in blue, violet, and ultraviolet regions.

Structural Evolution and Electronic Properties of V2Sin-/0 (n = 7-14) Clusters: Anion Photoelectron Spectroscopy and Theoretical Calculations.

A systematic study of the structures and electronic properties of V2-doped silicon clusters, V2Sin-/0 (n = 7-14), was carried out by anion photoelectron spectroscopic experiments combined with theoretical calculations. According to the experimental spectra of V2Sin- (n = 7-14) clusters, the V2Si12- cluster has the highest vertical detachment energy (VDE) of 3.66 eV, while V2Si7- and V2Si14- clusters have lower VDEs of 2.81 and 2.84 eV, respectively. The most stable structure searches find that two V atoms in the V2Sin- clusters with size n = 7 and 8 are located at the surface, while V2Sin- clusters with n ≥ 9 prefer cage-like structures. Based on the analysis of the structural evolution of V2Sin- (n = 9-14) clusters, it can be clearly seen how the antihexagonal prism with one V encapsulated in the cage is gradually built from n = 9 to 12 and further developed from n = 12 to 14 with the extra silicon atoms located at the surface of the Si12 cage. The molecular orbital and the atoms in molecule analysis of the V2Sin- (n = 7-14) anions demonstrate that the strong V-V bond and the delocalized interaction between the V2 moiety and the Sin ligand play a significant role in stabilizing the cluster structures. A strong linear correlation has been found between the Wiberg bond order of the V-V bond and the electron density at the V-V bond critical points.

Salviamilthone A-O, diterpenoid quinones from Salvia miltiorrhiza.

Fifteen undescribed diterpenoid quinones salviamilthone A-O (1-15), together with three known diterpenoid quinones (16-18), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthone J (10), salviamone (18) (10 µM) significantly increased cell viability and decreased the expression of IL-1ß in lipopolysaccharide-induced BEAS-2B cells. These data provide the molecular justification for the usage of Salvia miltiorrhiza in treating acute lung injury.

Small Leucine-Rich Proteoglycan PODNL1 Identified as a Potential Tumor Matrix-Mediated Biomarker for Prognosis and Immunotherapy in a Pan-Cancer Setting.

The podocan-like protein 1 (PODNL1), an important member of the small leucine-rich proteoglycans (SLRP) family, is a crucial component of the tumor microenvironment (TME). But its prognostic values and the role in the TME have not been systematically estimated in a pan-cancer setting. Targeting PODNL1, a systematic exploration into the TCGA datasets, reconciling with the analyses of single-cell transcriptomes and immunotherapeutic cohorts in cancers, and validation by tissue microarray-based multiplex immunofluorescence staining was performed. PODNL1 was significantly correlated with the poor prognosis and immunotherapeutic responses in various cancers. In-depth demonstration of molecular mechanisms indicated that PODNL1 expressions were notably positively correlated with cancer-associated fibroblast (CAF) infiltration levels in 33 types of cancers. It also positively correlated with the pan-fibroblast TGF-ß response signature score, and the hallmarks including TGF-ß, TNF-α, inflammatory response, apical junction, epithelial-mesenchymal transition and hedgehog in pan-cancer. Furthermore, high PODNL1 expressions were positively related with the regulation of tumor-promoting TGF-ß signaling through downregulating SMAD2/3:4 heterotrimer regulations transcription and up-regulating the pathway restricted SMAD protein phosphorylation. Single-cell transcriptome analyses and immunofluorescence validations indicated that PODNL1 was predominantly expressed in the cancer cells and CAFs in various cancers. Additionally, the heterogeneity of cancer genotype-phenotype cross-talking was also observed associated with PODNL1. Our systematic study indicates that PODNL1 plays an important role in the complex regulation network of tumor progression, and lays a foundation for further exploration to develop PODNL1 as a valuable matrix-mediated biomarker for cancer immunotherapy and prognosis in a pan-cancer setting.