The Arabidopsis Rab protein RABC1 affects stomatal development by regulating lipid droplet dynamics.

Lipid droplets (LDs) are evolutionarily conserved organelles that serve as hubs of cellular lipid and energy metabolism in virtually all organisms. Mobilization of LDs is important in light-induced stomatal opening. However, whether and how LDs are involved in stomatal development remains unknown. We show here that Arabidopsis thaliana LIPID DROPLETS AND STOMATA 1 (LDS1)/RABC1 (At1g43890) encodes a member of the Rab GTPase family that is involved in regulating LD dynamics and stomatal morphogenesis. The expression of RABC1 is coordinated with the different phases of stomatal development. RABC1 targets to the surface of LDs in response to oleic acid application in a RABC1GEF1-dependent manner. RABC1 physically interacts with SEIPIN2/3, two orthologues of mammalian seipin, which function in the formation of LDs. Disruption of RABC1, RABC1GEF1, or SEIPIN2/3 resulted in aberrantly large LDs, severe defects in guard cell vacuole morphology, and stomatal function. In conclusion, these findings reveal an aspect of LD function and uncover a role for lipid metabolism in stomatal development in plants.

Design and experiment of high-field asymmetric waveform ion mobility spectrometry chip based on an integrated temperature control printed circuit board structure.

RATIONALE: During the detection of volatile organic compounds (VOC) using high-field asymmetric waveform ion mobility spectrometry (FAIMS), the ambient temperature significantly impacts the accuracy of planar FAIMS. To mitigate the influence of ambient temperature on detection accuracy and enhance resolution, a FAIMS system based on the inner impedance characteristics of a printed circuit board (PCB) was designed for temperature control. METHODS: This study, conducted under standard atmospheric pressure, aimed to assess the signal stability of a planar FAIMS instrument with and without temperature control, and the effect of temperature change on the detection ability of acetone, ethanol, and their mixture was studied using PCB self-heating. RESULTS: Experimental results demonstrated that the base noise in FAIMS with temperature control was 0.2 pA, whereas that in FAIMS without temperature control was 1.8 pA. Notably, with increasing temperature, the detection ability of FAIMS changes accordingly. The optimal relative detection ability of acetone was observed when the electrode plate was heated to 45°C under an electric field of 15 kV/cm. CONCLUSIONS: This study provides a novel approach to improve the resolving power of FAIMS systems and their signal-to-noise ratio. The utilization of a PCB-based temperature control proved effective in stabilizing FAIMS signal characteristics and optimizing detection capabilities, particularly for VOCs such as acetone. These findings have significant implications for improving the accuracy and resolving power of FAIMS systems in VOC detection applications.

Biological Interactions Mediate Soil Functions by Altering Rare Microbial Communities.

Soil microbes, the main driving force of terrestrial biogeochemical cycles, facilitate soil organic matter turnover. However, the influence of the soil fauna on microbial communities remains poorly understood. We investigated soil microbiota dynamics by introducing competition and predation among fauna into two soil ecosystems with different fertilization histories. The interactions significantly affected rare microbial communities including bacteria and fungi. Predation enhanced the abundance of C/N cycle-related genes. Rare microbial communities are important drivers of soil functional gene enrichment. Key rare microbial taxa, including SM1A02, Gammaproteobacteria, and HSB_OF53-F07, were identified. Metabolomics analysis suggested that increased functional gene abundance may be due to specific microbial metabolic activity mediated by soil fauna interactions. Predation had a stronger effect on rare microbes, functional genes, and microbial metabolism compared to competition. Long-term organic fertilizer application increased the soil resistance to animal interactions. These findings provide a comprehensive understanding of microbial community dynamics under soil biological interactions, emphasizing the roles of competition and predation among soil fauna in terrestrial ecosystems.

[Consistency evaluation of multidimensional quality attributes of Atractylodis Macrocephalae Rhizoma by fusion of multi-source information].

The quality control of Chinese medicinal decoction pieces is one of the key tasks in the traditional Chinese medicine industry. In this study, multi-source information fusion was employed to fuse the data from near-infrared spectroscopy, electronic tongues, and other tests and establish an overall quality consistency evaluation method for Atractylodis Macrocephalae Rhizoma, which provided methodological support for the overall quality evaluation of Atractylodis Macrocephalae Rhizoma. The near-infrared spectroscopy information was measured in both static and dynamic states for 23 batches of Atractylodis Macrocephalae Rhizoma samples from different sources, and the electronic tongue sensory information, moisture content, and leachate content were measured. The overall quality of Atractylodis Macrocephalae Rhizoma was evaluated by multi-source information fusion. The results showed that the near-infrared spectroscopy information of 16122103, 801000509, 801000352, 701003656, HX21L01, and 160956 was different from that of other batches of Atractylodis Macrocephalae Rhizoma powder in the static state, and 701003298, 16122103, 701003656, 701003107, 801000229, and 18090404 were the different batches in the dynamic state. The moisture content showed no significant difference between batches. The leachate content in the batch 801000509 was different from that in other batches. The electronic tongue sensory information of 150721004, 151237, 160703004, HX21M01, HX21K04, HX21K01, and 601003516 was different from that of other batches. Furthermore, data layer fusion was employed to analyze the overall quality of Atractylodis Macrocephalae Rhizoma. Four batches, 150721004, HX21M01, HX21K04, and HX21K01, showed the parameters exceeding the 95% control limits and differed from the other samples in terms of the overall quality. This study integrated the information of moisture, near-infrared spectroscopy, and other sources to evaluate the quality consistency among 23 batches of Atractylodis Macrocephalae Rhizoma samples, which provides a reference for the quality consistency evaluation of Chinese medicinal decoction pieces.

Deflecting and routing nematicons via orientation programmable liquid crystal array.

By designing a liquid crystal cell with comb electrode structure, the alignment modulation of nematic liquid crystal in the cell can be realized after the electric field is applied. In different orientation regions, the incident laser beam can deflect at different angles. At the same time, by changing the incident angle of the laser beam, the reflection modulation of the laser beam on the interface of the liquid crystal molecular orientation change can be realized. Based on the above discussion, we then demonstrate the modulation of liquid crystal molecular orientation arrays on nematicon pairs. In different orientation regions of liquid crystal molecules, nematicon pairs can exhibit various combinations of deflections, and these deflection angles are modulable under external fields. Deflection and modulation of nematicon pairs have potential applications in optical routing and optical communication.

Strong bacterial stochasticity and fast fungal turnover in Taihu Lake sediments, China.

Understanding the assembly and turnover of microbial communities is crucial for gaining insights into the diversity and functioning of lake ecosystems, a fundamental and central issue in microbial ecology. The ecosystem of Taihu Lake has been significantly jeopardized due to urbanization and industrialization. In this study, we examined the diversity, assembly, and turnover of bacterial and fungal communities in Taihu Lake sediment. The results revealed strong bacterial stochasticity and fast fungal turnover in the sediment. Significant heterogeneity was observed among all sediment samples in terms of environmental factors, especially ORP, TOC, and TN, as well as microbial community composition and alpha diversity. For instance, the fungal richness index exhibited an approximate 3-fold variation. Among the environmental factors, TOC, TN, and pH had a more pronounced influence on the bacterial community composition compared to the fungal community composition. Interestingly, species replacement played a dominant role in microbial beta diversity, with fungi exhibiting a stronger pattern. In contrast, stochastic processes governed the community assembly of both bacteria and fungi, but were more pronounced for bacteria (R2 = 0.7 vs. 0.5). These findings deepen the understanding of microbial assembly and turnover in sediments under environmental stress and provide essential insights for maintaining the multifunctionality of lake ecosystems.

New Pyrroline Isolated from Antarctic Krill-Derived Actinomycetes Nocardiopsis sp. LX-1 Combining with Molecular Networking.

Antarctic krill (Euphausia superba) of the Euphausiidae family comprise one of the largest biomasses in the world and play a key role in the Antarctic marine ecosystem. However, the study of E. superba-derived microbes and their secondary metabolites has been limited. Chemical investigation of the secondary metabolites of the actinomycetes Nocardiopsis sp. LX-1 (in the family of Nocardiopsaceae), isolated from E. superba, combined with molecular networking, led to the identification of 16 compounds a-p (purple nodes in the molecular network) and the isolation of one new pyrroline, nocarpyrroline A (1), along with 11 known compounds 2-12. The structure of the new compound 1 was elucidated by extensive spectroscopic investigation. Compound 2 exhibited broad-spectrum antibacterial activities against A. hydrophila, D. chrysanthemi, C. terrigena, X. citri pv. malvacearum and antifungal activity against C. albicans in a conventional broth dilution assay. The positive control was ciprofloxacin with the MIC values of <0.024 µM, 0.39 µM, 0.39 µM, 0.39 µM, and 0.20 µM, respectively. Compound 1 and compounds 7, 10, and 11 displayed antifungal activities against F. fujikuroi and D. citri, respectively, in modified agar diffusion test. Prochloraz was used as positive control and showed the inhibition zone radius of 17 mm and 15 mm against F. fujikuroi and D. citri, respectively. All the annotated compounds a-p by molecular networking were first discovered from the genus Nocardiopsis. Nocarpyrroline A (1) features an unprecedented 4,5-dihydro-pyrrole-2-carbonitrile substructure, and it is the first pyrroline isolated from the genus Nocardiopsis. This study further demonstrated the guiding significance of molecular networking in the research of microbial secondary metabolites.

Printed Directional Bending Sensor with High Sensitivity and Low Hysteresis for Human Motion Detection and Soft Robotic Perception.

We present a high-performance flexible bending strain sensor for directional motion detection of human hands and soft robotic grippers. The sensor was fabricated using a printable porous conductive composite composed of polydimethylsiloxane (PDMS) and carbon black (CB). The utilization of a deep eutectic solvent (DES) in the ink formulation induced a phase segregation between the CB and PDMS and led to a porous structure inside the printed films after being vapored. This simple and spontaneously formed conductive architecture provided superior directional bend-sensing characteristics compared to conventional random composites. The resulting flexible bending sensors displayed high bidirectional sensitivity (gauge factor of 45.6 under compressive bending and 35.2 under tensile bending), negligible hysteresis, good linearity (>0.99), and excellent bending durability (over 10,000 cycles). The multifunctional applications of these sensors, including human motion detection, object-shape monitoring, and robotic perceptions, are demonstrated as a proof-of-concept.

Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts.

BACKGROUND: Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients. METHODS: The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket. RESULTS: Patients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib. CONCLUSION: Our findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs.

Study on detection of CNVs using human whole genome bisulfite sequencing data.

It has been reported that the aberrant DNA methylation may result in copy number variations (CNVs), and the CNVs may alter the levels of DNA methylation. Whole genome bisulfite sequencing (WGBS) is able to generate the sequencing data of DNAs, and shows the potential ability to detect CNVs. However, the evaluations and performances on the detections of CNVs using WGBS data is still unclear. In this study, five software with different strategies for CNV detections, e.g., BreakDancer, cn.mops, CNVnator, DELLY and Pindel, were selected to explore and benchmark the performances of CNV detections with WGBS data. Based on the real (2.62 billion reads) and simulated (12.35 billion reads) WGBS data of humans, we calculated the number, precision, recall, relative ability, memory usage, and running time of CNV detections by 150 times, and tried to figure out the optimal strategy for CNV detections with WGBS data. Based on the real WGBS data, Pindel detected the most deletions and duplications, CNVnator detected the deletions with the highest precision, cn.mops detected the duplications with the highest precision, Pindel detected the deletions with the highest recall, and cn.mops detected the duplications with the highest recall. Based on the simulated WGBS data, BreakDancer detected the most deletions, and cn.mops detected the most duplications. The CNVnator showed the highest precision and recall for both deletions and duplications. In real and simulated WGBS data, the ability of CNVnator to detect CNVs was likely to overtake that in the whole genome sequencing data. Additionally, DELLY and BreakDancer displayed the lowest peak of memory usage and the lest CPU runtime, while CNVnator expressed the highest peak of memory usage and the most CPU runtime. Taken together, CNVnator and cn.mops showed the excellent performances of CNV detections with WGBS data. These results suggested that it was feasible to detect CNVs using WGBS data, and provided the useful information to further investigate both CNVs and DNA methylation using WGBS data alone.

[Knowledge graph analysis of pyroptosis research in traditional Chinese medicine based on VOSviewer and CiteSpace].

To explore the research hotspots and frontier directions of pyroptosis in the field of traditional Chinese medicine(TCM), the authors searched CNKI and Web of Science for literature related to pyroptosis in TCM, screened literature according to the search strategy and inclusion criteria, and analyzed the publication trend of the included literature. VOSviewer was used to draw author cooperation and keyword co-occurrence network diagrams, and CiteSpace was employed for keyword clustering, emergence, and timeline view. Finally, 507 Chinese literature and 464 English literature were included, and it was found that the number of Chinese and English literature was increasing rapidly year by year. The co-occurrence of the authors showed that in terms of Chinese literature, there was a representative research team composed of DU Guan-hua, WANG Shou-bao and FANG Lian-hua, and for English literature, the representative research team was composed of XIAO Xiao-he, BAI Zhao-fang and XU Guang. The network visualization of Chinese and English keywords revealed that inflammation, apoptosis, oxidative stress, autophagy, organ damage, fibrosis, atherosclerosis, and ischemia-reperfusion injury were the primary research diseases and pathological processes in TCM; berberine, resveratrol, puerarin, na-ringenin, astragaloside Ⅳ, and baicalin were the representative active ingredients; NLRP3/caspase-1/GSDMD, TLR4/NF-κB/NLRP3, and p38/MAPK signaling pathways were the main research pathways. Keyword clustering, emergence, and timeline analysis indicated that the pyroptosis research in TCM focused on the mechanism of TCM monomers and compounds intervening in diseases and pathological processes. Pyroptosis is a research hotspot in the area of TCM, and the current discussion mainly focuses on the mechanism of the therapeutic effect of TCM.

Broad Impacts of Coronavirus Disease 2019 (COVID-19) Pandemic on Acute Respiratory Infections in China: An Observational Study.

BACKGROUND: To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs). METHODS: Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years. RESULTS: Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17.2% for RSV to -87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020-January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. CONCLUSIONS: Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

Effects of Trophic Level and Land Use on the Variation of Animal Antibiotic Resistome in the Soil Food Web.

In recent years, it has been increasingly recognized that soil animals are hidden reservoirs of antibiotic resistance genes (ARGs) and play a vital role in spreading ARGs in soil ecosystems. However, little is known about the variation of ARGs among different animals in the soil food web and effects of trophic levels and land uses on them. We characterized the antibiotic resistomes of 495 soil animal samples collected from six regions across China, including two different land uses. A total of 265 ARGs were detected in all animal samples, and relative abundances of ARGs in animals were significantly higher than in soils. In addition, significant differences in ARGs were observed among different animal groups. Twelve common ARGs were identified among all animal groups, accounting for 17.4% of total ARGs abundance. A positive and significant correlation was found between δ15N values (trophic level) and total ARGs abundance in animals. The relative abundance of ARGs in the soil food web from arable land was higher than forest land. Changes in soil antibiotics may indirectly affect animal resistome by altering soil ARGs. This study suggests that the risk of ARGs spreading through the food web is greater in arable than in forest ecosystems.

Decline of onset-to-diagnosis interval and its impacts on clinical outcome of COVID-19 in China: a nation-wide observational study.

BACKGROUND: To quantitatively assess the impact of the onset-to-diagnosis interval (ODI) on severity and death for coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study was conducted based on the data on COVID-19 cases of China over the age of 40 years reported through China's National Notifiable Infectious Disease Surveillance System from February 5, 2020 to October 8, 2020. The impacts of ODI on severe rate (SR) and case fatality rate (CFR) were evaluated at individual and population levels, which was further disaggregated by sex, age and geographic origin. RESULTS: As the rapid decline of ODI from around 40 days in early January to < 3 days in early March, both CFR and SR of COVID-19 largely dropped below 5% in China. After adjusting for age, sex, and region, an effect of ODI on SR was observed with the highest OR of 2.95 (95% CI 2.37‒3.66) at Day 10-11 and attributable fraction (AF) of 29.1% (95% CI 22.2‒36.1%) at Day 8-9. However, little effect of ODI on CFR was observed. Moreover, discrepancy of effect magnitude was found, showing a greater effect from ODI on SR among patients of male sex, younger age, and those cases in Wuhan. CONCLUSION: The ODI was significantly associated with the severity of COVID-19, highlighting the importance of timely diagnosis, especially for patients who were confirmed to gain increased benefit from early diagnosis to some extent.

Fatty acid-binding protein 7 triggers α-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress.

We previously show that fatty acid-binding protein 3 (FABP3) triggers α-synuclein (Syn) accumulation and induces dopamine neuronal cell death in Parkinson disease mouse model. But the role of fatty acid-binding protein 7 (FABP7) in the brain remains unclear. In this study we investigated whether FABP7 was involved in synucleinopathies. We showed that FABP7 was co-localized and formed a complex with Syn in Syn-transfected U251 human glioblastoma cells, and treatment with arachidonic acid (100 M) significantly promoted FABP7-induced Syn aggregation, which was associated with cell death. We demonstrated that synthetic FABP7 ligand 6 displayed a high affinity against FABP7 with Kd value of 209 nM assessed in 8-anilinonaphthalene-1-sulfonic acid (ANS) assay; ligand 6 improved U251 cell survival via disrupting the FABP7-Syn interaction. We showed that activation of phospholipase A2 (PLA2) by psychosine (10 M) triggered oligomerization of endogenous Syn and FABP7, and induced cell death in both KG-1C human oligodendroglia cells and oligodendrocyte precursor cells (OPCs). FABP7 ligand 6 (1 M) significantly decreased Syn oligomerization and aggregation thereby prevented KG-1C and OPC cell death. This study demonstrates that FABP7 triggers α-synuclein oligomerization through oxidative stress, while FABP7 ligand 6 can inhibit FABP7-induced Syn oligomerization and aggregation, thereby rescuing glial cells and oligodendrocytes from cell death.

Genus Nocardiopsis: A Prolific Producer of Natural Products.

Actinomycetes are currently one of the major sources of bioactive secondary metabolites used for medicine development. Accumulating evidence has shown that Nocardiopsis, a key class of actinomycetes, has the ability to produce novel bioactive natural products. This review covers the sources, distribution, bioactivities, biosynthesis, and structural characteristics of compounds isolated from Nocardiopsis in the period between March 2018 and 2021. Our results reveal that 67% of Nocardiopsis-derived natural products are reported for the first time, and 73% of them are isolated from marine Nocardiopsis. The chemical structures of the Nocardiopsis-derived compounds have diverse skeletons, concentrating on the categories of polyketides, peptides, terphenyls, and alkaloids. Almost 50% of the natural products isolated from Nocardiopsis have been discovered to display various bioactivities. These results fully demonstrate the great potential of the genus Nocardiopsis to produce novel bioactive secondary metabolites that may serve as a structural foundation for the development of novel drugs.

ß-Caryophyllene Acts as a Ferroptosis Inhibitor to Ameliorate Experimental Colitis.

Macrophage infiltration is one of the main pathological features of ulcerative colitis (UC) and ferroptosis is a type of nonapoptotic cell death, connecting oxidative stress and inflammation. However, whether ferroptosis occurs in the colon macrophages of UC mice and whether targeting macrophage ferroptosis is an effective approach for UC treatment remain unclear. The present study revealed that macrophage lipid peroxidation was observed in the colon of UC mice. Subsequently, we screened several main components of essential oil from Artemisia argyi and found that ß-caryophyllene (BCP) had a good inhibitory effect on macrophage lipid peroxidation. Additionally, ferroptotic macrophages were found to increase the mRNA expression of tumor necrosis factor alpha (Tnf-α) and prostaglandin-endoperoxide synthase 2 (Ptgs2), while BCP can reverse the effects of inflammation activated by ferroptosis. Further molecular mechanism studies revealed that BCP activated the type 2 cannabinoid receptor (CB2R) to inhibit macrophage ferroptosis and its induced inflammatory response both in vivo and in vitro. Taken together, BCP potentially ameliorated experimental colitis inflammation by inhibiting macrophage ferroptosis. These results revealed that macrophage ferroptosis is a potential therapeutic target for UC and identified a novel mechanism of BCP in ameliorating experimental colitis.

[Mechanism and experimental verification of "Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus" combination in treatment of acute gouty arthritis based on network pharmacology].

Based on network pharmacology, the mechanism of Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus(PL) combination against acute gouty arthritis(AGA) was explored and preliminarily verified by animal experiment. The chemical components and corresponding targets of PL were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The active components with oral bioavailability(OB)≥30% and drug-likeness(DL)≥0.18 were screened based on literature, and the related protein targets were collected. Then the protein targets were standardized with the help of UniProt database. The AGA-related targets were searched from GeneCards, NCBI, and DrugBank. The common targets of the disease and the medicinals were yielded by FunRich V3, and the protein-protein interaction(PPI) network was constructed to screen the key targets, followed by Gene Ontology(GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the key targets. Afterwards, some of the key targets were verified by sodium urate crystal-induced AGA mouse model. A total of 25 active components and 287 targets of PL, 811 targets of AGA, and 88 common targets were screened out. PPI network analysis showed that tumor necrosis factor(TNF), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) may be the core targets of PL in the treatment of AGA. The key targets were mainly involved in 566 GO terms(P<0.05), including multiple biological processes such as inflammatory response and immune response. Moreover, they were related to 116 KEGG pathways and these pathways were involved in inflammation and immunity, mainly including NOD-like receptor signaling pathway and TNF signaling pathway. Animal experiment confirmed that PL can alleviate ankle swelling, improve abnormal gait, and down-regulate the protein expression of TNF-α, IL-6, and IL-1ß in AGA mice, indicating that PL can treat AGA through TNF-α, IL-6, and IL-1ß and the feasibility of network pharmacology to predict drug targets. This study preliminarily discussed the key targets and biological signaling pathways involved in the treatment of AGA with PL combination, which reflected the multi-pathway and multi-target action characteristics of Chinese medicine. Moreover, this study laid a scientific basis for research on the treatment of AGA with PL combination, as well as the mechanism of action.

[Evidence mapping of clinical research on 20 Chinese patent medicines for hypertension].

In this study, evidence mapping was employed to sort out and summarise the evidence from clinical studies of Chinese patent medicines for hypertension and to understand the evidence distribution in related studies. Chinese patent medicines for hypertension were searched from Medicine Catalogue for National Basic Medical Insurance, Employment Injury Insurance, and Maternity Insu-rance(2021) and Chinese Pharmacopoeia(2020). Relevant articles(published from January 1, 2016 to February 14, 2022) were retrieved from Cochrane Library, PubMed, Web of Science, CNKI, Wanfang, VIP, and SinoMed. Then, the evidence distribution was analysed based on description, tables, and bubble charts. A total of 31 Chinese patent medicines were identified and 20 were finally included, involving 111 articles. The basic information of the 20 Chinese patent medicines, the number of related articles, the hypertension staging and traditional Chinese medicine(TCM) syndrome types of the subjects, sample size, interventions, and outcome indicators were compared. The results showed Chinese patent medicines with the function of pacifying liver and eliminating wind were frequently studied, and most of them were single-center, small-sample, short-period randomized controlled trials. They failed to highlight the key and advantages of TCM. A wide variety of outcome indicators were involved, and in addition to blood pressure, surrogate outcome indicators and composite outcome indicators were emphasized. However, health economic indicators, quality of life, and damage to target organs such as blood vessels and heart, were rarely used.

Differential responses of bone to angiotensin II and angiotensin(1-7): beneficial effects of ANG(1-7) on bone with exposure to high glucose.

Osteoporosis, diabetes, and hypertension are common concurrent chronic disorders. This study aimed to explore the respective effects of angiotensin II (ANG II) and angiotensin(1-7) [ANG(1-7)], active peptides in the renin-angiotensin system, on osteoblasts and osteoclasts under high-glucose level, as well as to investigate the osteo-preservative effects of ANG II type 1 receptor (AT1R) blocker and ANG(1-7) in diabetic spontaneously hypertensive rats (SHR). ANG II and ANG(1-7), respectively, decreased and increased the formation of calcified nodules and alkaline phosphatase activity in MC3T3-E1 cells under high-glucose level, and respectively stimulated and inhibited the number of matured osteoclasts and pit resorptive area in RANKL-induced bone marrow macrophages. Olmesartan and Mas receptor antagonist A779 could abolish those effects. ANG II and ANG(1-7), respectively, downregulated and upregulated the expressions of osteogenesis factors in MC3T3-E1 cells. ANG II promoted the expressions of cathepsin K and MMP9 in RAW 264.7 cells, whereas ANG(1-7) repressed these osteoclastogenesis factors. ANG II rapidly increased the phosphorylation of Akt and p38 in RAW 264.7 cells, whereas ANG(1-7) markedly reduced the phosphorylation of p38 and ERK under high-glucose condition. After treatments of diabetic SHR with valsartan and ANG(1-7), a significant increase in trabecular bone area, bone mineral density, and mechanical strength was only found in the ANG(1-7)-treated group. Treatment with ANG(1-7) significantly suppressed the increase in renin expression and ANG II content in the bone of SHR. Taken together, ANG II/AT1R and ANG(1-7)/Mas distinctly regulated the differentiation and functions of osteoblasts and osteoclasts upon exposure to high-glucose condition. ANG(1-7) could protect SHR from diabetes-induced osteoporosis.