Two new sesterterpenoids from Atractylodes japonica Koidz. ex Kitam.

Two new sesterterpenoids, atractylodes japonica terpenoid acid I (1) and atractylodes japonica terpenoid aldehyde I (2), were isolated from the rhizomes of Atractylodes japonica Koidz. ex Kitam together with ten known compounds (3-12). Their structures were elucidated on the basis of comprehensive spectroscopic analysis (1D/2D NMR, HRESIMS and IR). In addition, all of these isolated compounds were evaluated for their cytotoxic activities against human gastric cancer cell MGC-803 and human hepatocellular cancer cell HepG-2. Most of them exhibited moderate to weak inhibitory effects with IC50 values in the range of 25.15-88.85 µM except for 9-12.

Peptide targeting improves the delivery and therapeutic index of glucocorticoids to treat rheumatoid arthritis.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by excessive inflammation in the joints. Glucocorticoid drugs are used clinically to manage RA symptoms, while their dosage and duration need to be tightly controlled due to severe adverse effects. Using dexamethasone (DEX) as a model drug, we explored here whether peptide-guided delivery could increase the safety and therapeutic index of glucocorticoids for RA treatment. Using multiple murine RA models such as collagen-induced arthritis (CIA), we found that CRV, a macrophage-targeting peptide, can selectively home to the inflammatory synovium of RA joints upon intravenous injection. The expression of the CRV receptor, retinoid X receptor beta (RXRB), was also elevated in the inflammatory synovium, likely being the basis of CRV targeting. CRV-conjugated DEX increased the accumulation of DEX in the inflamed synovium but not in healthy organs of CIA mice. Therefore, CRV-DEX demonstrated a stronger efficacy to suppress synovial inflammation and alleviate cartilage/bone destruction. Meanwhile, CRV conjugation reduced immune-related adverse effects of DEX even after a long-term use. Last, we found that RXRB expression was significantly elevated in human patient samples, demonstrating the potential of clinical translation. Taken together, we provide a novel, peptide-targeted strategy to improve the therapeutic efficacy and safety of glucocorticoids for RA treatment.

Seasonal changes of prokaryotic microbial community structure in Zhangjiayan Reservoir and its response to environmental factors.

As a typical sub-deep reservoir in the upper reaches of the Yangtze River in the southwest region, Zhangjiayan Reservoir is also an important source of drinking water. Exploring the role of microorganisms in the material cycle of water bodies is of great significance for preventing the exacerbation of eutrophication in the reservoir. In this study, water samples from the overlying water of five points in the reservoir were collected four times in spring (April), summer (July), autumn (November), and winter (January) of 2022-2023 using a gas-tight water sampler. Physicochemical factors were measured, and the microbial community structure was analyzed by high-throughput MiSeq sequencing of the V3-V4 hypervariable region of 16S rRNA gene in order to explore the relationship between physicochemical factors and microbial community structure and the dominant microbial populations that affect eutrophication of the reservoir. The following results were obtained through analysis. Among the 20 overlying water samples from Zhangjiayan Reservoir, a total of 66 phyla, 202 classes, 499 orders, 835 families, 1716 genera, and 27,904 ASVs of the bacterial domain were detected. The phyla Proteobacteria and Actinobacteria were dominant in the microbial community of the overlying water in Zhangjiayan Reservoir. At the genus level, hgcI_clade and Actinobacteria had the highest abundance and was the dominant population. The microbial community in the water of Zhangjiayan Reservoir has a high level of diversity. The diversity index ranked by numerical order was winter > autumn > summer > spring. Significant differences were found in the composition and structure of the microbial community between the spring/summer and autumn/winter seasons (p < 0.05). Total phosphorus, dissolved total phosphorus, soluble reactive phosphorus, and dissolved oxygen have a significant impact on the composition and structure of the microbial community (p < 0.01). The bacterial community in the overlying water of Zhangjiayan Reservoir showed a mainly positive correlation. Sphingomonas, Brevundimonas, and Blastomonas were the central populations of the bacterial community in the overlying water of Zhangjiayan Reservoir. This study indicates that environmental factors, such as phosphorus and other nutrients, have a significant impact on the formation of the microbial community structure in different seasons. Sphingomonas, Brevundimonas, and Blastomonas are key populations that may have a significant impact on eutrophication in Zhangjiayan Reservoir.

Eight-month intensive meditation-based intervention improves refractory hallucinations and delusions and quality of life in male inpatients with schizophrenia: a randomized controlled trial.

AIM: This study investigated the impact of an 8-month daily-guided intensive meditation-based intervention (iMI) on persistent hallucinations/delusions and health-related quality of life (QoL) in male inpatients with schizophrenia with treatment-refractory hallucinations and delusions (TRHDs). METHODS: A randomized controlled trial assigned 64 male inpatients with schizophrenia and TRHD equally to an 8-month iMI plus general rehabilitation program (GRP) or GRP alone. Assessments were conducted at baseline and the third and eighth months using the Positive and Negative Syndrome Scale (PANSS), 36-Item Short Form-36 (SF-36), and Five Facet Mindfulness Questionnaire (FFMQ). Primary outcomes measured PANSS reduction rates for total score, positive symptoms, and hallucinations/delusions items. Secondary outcomes assessed PANSS, SF-36, and FFMQ scores for psychotic symptoms, health-related QoL, and mindfulness skills, respectively. RESULTS: In the primary outcome, iMI significantly improved the reduction rates of PANSS total score, positive symptoms, and hallucination/delusion items compared with GRP at both the third and eighth months. Treatment response rates (≥25% reduction) for these measures significantly increased in the iMI group at the eighth month. Concerning secondary outcomes, iMI significantly reduced PANSS total score and hallucination/delusion items, while increasing scores in physical activity and mindfulness skills at both the third and eighth months compared with GRP. These effects were more pronounced with an 8-month intervention compared with a 3-month intervention. CONCLUSIONS: An iMI benefits patients with TRHDs by reducing persistent hallucinations/delusions and enhancing health-related QoL. Longer iMI duration yields superior treatment outcomes.

Protective Mechanisms of Juncus effusus and Carbonized Juncus effusus against D-Galactosamine-Induced Acute Liver Injury in Mice.

This study investigated the hepatoprotective effects of Juncus effusus (J. effusus) and Carbonized J. effusus against liver injury caused by D-galactosamine (D-GalN) in mice. J. effusus and Carbonized J. effusus were administered by gavage once daily starting seven days before the D-GalN treatment. The results of the study indicated that J. effusus and Carbonized J. effusus suppressed the D-GalN-induced generation of serum alanine transaminase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) was observed. The values of superoxide dismutase (SOD) exhibited an increase. In addition, J. effusus and Carbonized J. effusus promoted the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1) as well as the mRNA expression of Nrf2, HO-1, NQO-1 and Glutamate cysteine ligase catalytic subunit (GCLC). The compressed Carbonized J. effusus demonstrated the optimum impact. These results suggest that J. effusus and Carbonized J. effusus protect against D-GalN-induced acute liver injury through the activation of the Nrf2 pathway.

Fingerprint analysis of dang-gui-Si-Ni decoction and its anticoagulant activity in vivo-in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Dang-Gui-Si-Ni (DGSN) decoction is a classic prescription in the clinical practice of traditional Chinese Medicine (TCM). DGSN decoction is often used to relieve symptoms of cold coagulation and blood stasis recorded by Treatise on Febrile Diseases (Shang Han Lun) and treat Raynaud's disease, dysmenorrhea, arthritis, migraine in TCM clinic. Accumulated evidences have suggested that this diseases are related to microcirculation disturbance. However, the anticoagulant activity and underlying mechanisms of DGSN decoction responsible for the therapeutic not well understood. AIM OF THE STUDY: The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas. MATERIALS AND METHODS: The chemical components of DGSN decoction were analyzed by HPLC and its fingerprint similarity were evaluated by "Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software (2012 Edition)". The anticoagulant activity of DGSN decoction was assessed by measuring four coagulation factors (PT, TT, APTT, FIB) in vitro. Zebrafish thrombosis model induced by punatinib was established to evaluate the activity of improving microvascular hemodynamics in vivo. Quantitative real-time polymerase chain reaction (q-PCR) were adopted to compare the changes in the RNA expression levels of coagulation factor II (FII), VII (FVII), IX (FIX) and X (FX) in zebrafish thrombosis model. RESULTS: The fingerprint similarity evaluation method of DGSN decoction was established. The results showed that 18 samples had higher similarity (S1-S18 > 0.878). Pharmacodynamic results showed that DGSN decoction could extend PT, TT and APTT, and reduce FIB content in vitro. Meanwhile, it markedly enhanced the cardiac output and blood flow velocity at low dosage (500 µg mL-1) in vivo. q-PCR data demonstrated that DGSN decoction (500 µg mL-1) could downregulate the RNA expression of FII, FVII, FIX and FX. Interestingly, there were a bidirectional regulation of FII, FIX and FX in a certain concentration range. In general, DGSN decoction can significantly improve hemodynamics and downregulate coagulation factors, and the results were consistent both in vitro - in vivo. CONCLUSION: The fingerprint study provide a new perspective for improving the quality control of DGSN decoction. DGSN decoction possess anticoagulant activity by regulating multiple coagulation factors simultaneously. Thus, it has the potential to develop into the novel raw material of anticoagulant drugs.

Short-Term Effects of Combining Moxibustion Therapy and Gua sha on Post-Multiple Cerebral Infarction Rehabilitation.

Objective: This study aimed to assess the impact of combined moxibustion therapy and Gua sha on enhancing functional independence, reducing fall risk, and alleviating pain in patients undergoing post-rehabilitation for multiple cerebral infarctions. Methods: In a prospective clinical trial, 67 patients diagnosed with multiple cerebral infarctions (age range: 40 to 93 years) were enrolled. Baseline health characteristics included a median hospital stay of 10 days, prevalent medical conditions such as hypertension (64.18%), and various comorbidities like spondylosis (17.91%) and heart disease (14.93%). Patients received moxibustion treatment daily for 20-30 minutes on specific acupoints of the upper and lower extremities. Additionally, Gua sha therapy targeting the the head, back, chest, abdomen, and selected acupoints was administered twice a week with an interval of 3 to 4 days. Assessments included Barthel Index (BI) for functional independence, Morse Fall Scale (MFS) for fall risk, and Visual Analogue Scale (VAS) for pain intensity before and after the intervention. Results: After one week of rehabilitation, significant improvements were observed in the patient's functional independence, as indicated by a median BI score of 100 (IQR: 95-100), compared to the pre-rehabilitation median score of 95 (IQR: 90-100). The MFS score also showed a significant decrease after rehabilitation, with a median score of 35 (IQR: 35-45) compared to the pre-rehabilitation median score of 45 (IQR: 35-45). Additionally, pain intensity significantly decreased, with a median VAS score of 0 (range: 0-2) after rehabilitation, compared to the pre-rehabilitation median score of 0 (range: 0-3). Conclusion: Combined moxibustion therapy and Gua sha demonstrated positive effects on functional independence, fall risk reduction, and pain alleviation in post-rehabilitation for multiple cerebral infarctions. These findings suggest the potential of moxibustion and Gua sha as complementary interventions in stroke rehabilitation. The observed improvements in functional independence, fall risk, and pain underscore the potential benefits of these therapies for patients with multiple cerebral infarctions. Further exploration could delve into long-term effects, larger-scale trials, and mechanistic studies to elucidate the underlying pathways of efficacy.

Inhibition of p38 MAPK/NF-κB p65 signaling pathway activity by rare ginsenosides ameliorates cyclophosphamide-induced premature ovarian failure and KGN cell injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Mey., one of the most used herbs in the world, shows effective treatment in reproductive injury. Recent studies have proven that the processed product, red ginseng, which is more active than ginseng itself. Therefore, it is speculated that its main functional component, rare ginsenosides (heat-transformed saponin, HTS), may be effective in treating premature ovarian failure (POF), but its efficacy has not yet been experimentally confirmed. AIM OF THE STUDY: To evaluate whether HTS could attenuate cyclophosphamide-induced inflammation and oxidative damage in POF model rats and the human granulosa-like KGN cell line and protect granulosa cell proliferation. MATERIAL AND METHODS: HTS were isolated from ginsenosides and high performance liquid chromatography (HPLC) analysis was used to analyze the HTS components. Cyclophosphamide (CP) was used to establish a POF rat model and KGN cell injury model. Reactive oxygen species (ROS) and antioxidant enzyme production was determined using specific assays, while inflammatory cytokine secretion was measured by enzyme-linked immunosorbent assay (ELISA). The proliferative function of granulosa cells was assessed using high-content screening and immunohistochemistry to determine the Ki67 protein level. Protein expression in ovarian tissues and KGN cells was analyzed by Western blotting, quantitative real-time PCR (qRT-PCR) was used to determine the transcriptional changes in ovarian tissues and KGN cells. RESULTS: In CP-treated POF model rats, HTS significantly decreased malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels, increased glutathione oxidase (GSH) levels, and upregulated Ki67 expression in ovarian granulosa cells. In addition, HTS significantly increased cell survival and Ki67 expression levels in CP-treated cells, and superoxide dismutase (SOD) levels were significantly increased. HTS significantly downregulated IL-6, TNF-α, and interleukin-1ß (IL-1ß) mRNA expression and significantly inhibited nuclear factor kappa-B p65 (NF-κB p65) and p38 mitogen activated protein kinase (p38 MAPK) phosphorylation in POF model rats and KGN cells. Moreover, NF-κB p65 and p38 MAPK levels were significantly increased in ovarian granulosa cells. p65 and p38 protein and gene expression was significantly downregulated. CONCLUSION: HTS ameliorated CP-induced POF and human granulosa cell injury, possibly by inhibiting inflammation and oxidative damage mediated by the p38 MAPK/NF-κB p65 signaling pathway.

Quantifying carotid stiffness in chronic kidney disease using ultrafast ultrasound imaging.

Background: The mortality and disability of chronic kidney disease (CKD) are highly linked to the incidence of atherosclerotic cardiovascular events. Numerous clinical biochemical indicators of renal function often only increase in advanced stages of CKD, driving an urgent need for reliable indicators of atherosclerosis in early CKD. Ultrafast pulse wave velocity (ufPWV) can evaluate the stiffness of the straight carotid in vivo and quantitatively reflect the degree of early atherosclerosis. However, the use of ufPWV in CKD has not yet been reported. In this study, we aimed to explore the association between carotid stiffness, quantified using ufPWV, and renal function in CKD patients. Methods: This cross-sectional study enrolled a total of 582 participants between March 2017 and May 2022 in the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Among those, 205 individuals without a history of CKD and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were included as controls. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) expert group of the American Kidney Foundation staging for CKD, 44 stages 1 and 2 CKD patients were included in the early CKD group, whereas 49 stages 3, 4, and 5 CKD patients were included in the advanced CKD group. Clinical and serum parameters, ultrasonic characteristics including carotid intima-media thickness (cIMT), and pulse wave velocity at the beginning of systole (PWV-BS) and pulse wave velocity at the end of systole (PWV-ES) of systole were analyzed. One-way analysis of variance (ANOVA) and least significant difference (LSD) tests were performed to compare cIMT, PWV-BS, and PWV-ES among subgroups in pairs. Pearson's correlation analysis, scatter plots, and subgroups correlation analysis were used to determine the relationships among ultrasound characteristics (cIMT, PWV-BS, PWV-ES), and major cardiovascular risk factors. Results: PWV-BS and PWV-ES for the early and advanced CKD groups were significantly higher than those for controls (all P<0.05). PWV-ES had the greatest correlation with age (r=0.474, P<0.001). PWV-ES had the greatest increase with age in the early CKD group (r=0.698, P<0.001). Conclusions: ufPWV can be used for the quantitative evaluation of carotid stiffness in CKD patients. PWV-ES may be more advantageous in the assessment of carotid atherosclerosis in early CKD patients.

Polydopamine nanoplatform with near infrared light and pH dual stimuli-responsive for chemo-photothermal cancer therapy.

Photothermal agent accompanying with thermally responsive materials, displays well controlled drug release property, which is well-received as an outstanding design strategy for simultaneous photothermal/chemotherapy in cancer. Cyanine dye, as the prestigious photothermal agent has shown great potential due to its preeminent near-infrared absorbance and excellent thermal conversion efficiency. However, their inherent defect such as inferior photothermal stability, high leakage risk and poor therapy efficacy limit their further application in cancer therapy. Hence, a facile and universal strategy to make up these deficiencies is developed. Chemotherapeutic drug DOX and cyanine dye were loaded into polydopamine (PDA) nanoparticles. The PDA encapsulation dramatically improved the photothermal stability of cyanine dye. Attributed by the PDA structure feature, the thermo-sensitive small molecule glyamine (Gla) is introduced into the PDA surface to lessen leakage. The Gla can form a dense encapsulation layer on the dopamine surface through hydrogen bond. This newly fabricated Cyanine/DOX@PDA-Gla nanopaltform is characterized with NIR light/pH dual-responsive property, high NIR photothermal conversion performance and fluorescence guided chemo-photothermal therapy.

Antibacterial and antioxidant activities of a novel biosynthesized selenium nanoparticles using Rosa roxburghii extract and chitosan: Preparation, characterization, properties, and mechanisms.

Developing efficient and safe antibacterial agents to inhibit pathogens including Physalospora piricola and Staphylococcus aureus is of great importance. Herein, a novel compound composed of Rosa roxburghii procyanidin, chitosan and selenium nanoparticle (RC-SeNP) was bio-synthesized, with the average diameter and zeta potential being 84.56 nm and -25.60 mV, respectively. The inhibition diameter of the RC-SeNP against P. piricola and S. aureus reached 18.67 mm and 13.13 mm, and the maximum scavenging activity against DPPH and ABTS reached 96.02% and 98.92%, respectively. Moreover, the RC-SeNP completely inhibited the propagation P. piricola and S. aureus on actual apples, suggesting excellent in vivo antimicrobial capacity. The transcriptome analysis and electron microscope observation indicated that the antibacterial activity would be attributed to adhering to and crack the cell walls as well as damage the cytomembrane and nucleus. Moreover, the RC-SeNP effectively maintained the vitamin C, total acid, and water contents of red bayberry, demonstrating potential application for fruit preservation. At last, the RC-SeNP showed no cell toxicity and trace selenium residual dose (0.03 mg/kg on apple, 0.12 mg/kg on red bayberry). This study would enlighten future development on novel nano-bioantibacterial agents for sustainable agriculture.

Amphiphilic polymeric nanodrug integrated with superparamagnetic iron oxide nanoparticles for synergistic antibacterial and antitumor therapy of colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies that can be influenced by Fusobacterium nucleatum (Fn), a bacterium that promotes tumor development and chemoresistance, resulting in limited therapeutic efficacy. Traditional antibiotics cannot effectively eliminate Fn at tumor site due to issues like biofilm formation, while chemotherapy alone fails to suppress tumor progression. Therefore, the development of new methods to eliminate Fn and promote antitumor efficacy is of great significance for improving the outcome of CRC treatment. Herein, we developed a nanodrug (OPPL) that integrates oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) and an amphiphilic polymer (PPL) to deliver the platinum prodrug and antimicrobial lauric acid (LA) for enhancing the treatment of CRC. We demonstrated that OPPL can synergistically enhance antibacterial and biofilm disruption activities against Fn along with the antimicrobial LA by producing reactive oxygen species (ROS) through its peroxidase-like activity. Furthermore, the OPPL nanodrug can increase intracellular ROS, promote lipid peroxides and deplete glutathione, leading to ferroptosis. By combining chemotherapy and induced ferroptosis, the OPPL nanodrug exhibited high cytotoxicity against CRC cells. In vivo studies showed that the OPPL nanodrug could enhance tumor accumulation, enable magnetic resonance imaging, suppresse tumor growth, and inhibit growth of intratumor Fn. These results suggest that OPPL is an effective and promising candidate for the treatment of Fn-infected CRC. STATEMENT OF SIGNIFICANCE: The enrichment of Fusobacterium nucleatum (Fn) in colorectal cancer is reported to exacerbate tumor malignancy and is particularly responsible for chemoresistance. To this respect, we strategically elaborated multifaceted therapeutics, namely OPPL nanodrug, combining oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) with a polymer containing a platinum prodrug and antimicrobial lauric acid. The O-SPION components exert distinctive peroxidase-like activity, capable of stimulating Fenton reactions selectively in the tumor microenvironment, consequently accounting for the progressive production of reactive oxygen species. Hence, O-SPIONs have been demonstrated to not only supplement the antimicrobial activities of lauric acid in overcoming Fn-induced chemoresistance but also stimulate potent tumor ferroptosis. Our proposed dual antimicrobial and chemotherapeutic nanodrug provides an appreciable strategy for managing challenging Fn-infected colorectal cancer.

Discovery of new triterpenoids from Leptopus clarkei and their antiproliferative activity on cancer cells.

Two new triterpenoids (1-2), along with six known analogues (3-8) were obtained from the dried whole plant of Leptopus clarkei. Compound 1 is a 3,4-seco-lupane-type triterpenoid, and compound 2 is a phenylpropanoid-conjugated pentacyclic triterpenoid possessing trans-p-coumaroyl unit attached to oleanane-type skeleton. This is the first report on chemical investigation of the L. clarkei, and the triterpenoid derivatives were found in this plant for the first time. The structures of the new compounds were unequivocally elucidated by HRESIMS and 1D/2D NMR data. Additionally, the isolated compounds were evaluated for theircytotoxicities against four cancer cell lines including HepG2, MCF-7, A549 and HeLa. Notably, compound 2 exhibited the most significant antiproliferative activity with IC50 less than 20 µM for four cancer lines.

First Report of Colletotrichum siamense Causing Anthracnose on Syzygium grijsii in China.

Syzygium grijsii is an evergreen shrub belonging to the family Myrtaceae, and widely cultivated in southern China as an ornamental medicinal plant. In May 2022, anthracnose symptoms were observed on leaves of S. grijsii planted in a nursery (N22°55'46″, E108°22'11″) in Nanning, Guangxi Province, China. More than 30% of leaves were infected. Initially, irregular brown spots (1 to 2 mm in diameter) formed on the leaves, with a slight depression in the center, then expanded into large, dark-brown lesions. In severe infections, lesions coalesced and covered the entire leaf, causing wilt and fall off the plant. To identify the pathogen, 30 diseased leaves were collected from five plants. Leaf tissues (5 × 5 mm) were cut from the infected margins, surface sterilized (75% ethanol 10 s, 2% NaClO 5 min, rinsed three times with sterile water), then placed on potato dextrose agar (PDA), and incubated at 28℃ in darkness. After 5 days, 16 fungal isolates with similar morphology were obtained from 30 plated tissues. Colonies on PDA were abundant with grayish-white fluffy mycelia, and yellowish-white on the back. Conidia were one-celled, hyaline, smooth-walled, cylindrical with narrowing at the center, blunt at the ends, and ranged from 11.35 to 22.14 × 4.88 to 7.67 µm (n=100). Morphological characteristics of the isolates were similar to the descriptions of Colletotrichum sp. (Prihastuti et al. 2009). Five representative isolates (Cs34, Cs31, Cs32, Cs33 and Cs35), which were preserved in the Guangxi Key Laboratory of Biology for Crop Diseases and Insect Pests, were selected for molecular identification. The ITS (Nos. OQ618199, OR539576 to OR539579), TUB2 (Nos. OQ630972, OR545076 to OR545079), ACT (Nos. OQ685919, OR545060 to OR545063), CHS-1 (Nos. OQ685917, OR545068 to OR545071), GAPDH (Nos. OQ685916, OR545072 to OR545075), and CAL (Nos. OQ685918, OR545064 to OR545067) sequences showed >99% identity to those of Colletotrichum siamense ex-type culture ICPM 18578 (Nos. JX010171, JX009924, JX009714 and JX009518) and strain C1315.2 (Nos. JX009865 and JX010404) in GenBank. Multigene phylogenetic analyses (ITS, TUB, ACT, CHS-1, GAPDH, and CAL) using the Maximum likelihood method indicated that the 5 isolates were clustered with C. siamense. To perform pathogenicity tests, three one-year-old healthy S. grijsii plants were inoculated with conidial suspension (1 × 106 conidia/ml) of isolate Cs34 by brushing gently with a soft paintbrush, each plant was inoculated with 3 leaves. The same number of plants were inoculated with sterile water as control, and pathogenicity tests were performed three times. All plants were kept in an artificial climatic box at 28℃, with a 90% humidity and a 12 h light/dark cycle. Similar symptoms to those of the field were observed on all inoculated leaves after 5 days, whereas controls remained symptomless. Reisolated fungi from the diseased leaves were confirmed to be C. siamense by morphology and molecular characterization, confirming Koch's postulates. C. siamense has been reported causing anthracnose on Crinum asiaticum (Khoo et al. 2022) in Malaysia, and Erythrina crista-galli in China (Li et al. 2021). To our knowledge, this is the first report of C. siamense causing anthracnose on S. grijsii in China. The results of pathogen identification provide crucial information for control strategies of the disease.

[Research progress in quality control of Bufonis Venenum in preparations].

Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.

[Chemical composition and antioxidant activity of different parts of Prunella vulgaris by UPLC-Q-TOF-MS/MS and UPLC].

Prunellae Spica is the dried spica of Prunella vulgaris belonging to Labiatae and it is widely used in pharmaceutical and general health fields. As a traditional Chinese medicine cultivated on a large scale, it produces a large amount of non-medicinal parts, which are discarded because they are not effectively used. To analyze the chemical constituents in the different samples from spica, seed, stem, and leaf of P. vulgaris, and explore the application value and development prospect of these parts, this study used ultrahigh performance liquid chromatography-tandem quadrupoles time of flight mass spectrometry(UPLC-Q-TOF-MS/MS) to detect chemical constituents in different parts of P. vulgaris. As a result, 117 compounds were detected. Among them, 87 compounds were identified, including 32 phenolic acids, 8 flavonoids, and 45 triterpenoid saponins. Some new triterpenoid saponins containing the sugar chain with 4-6 sugar units were found. Further, multivariate statistical analysis was conducted on BPI chromatographic peaks of multiple batches of different parts, and the results showed that spica had the most abundant chemical constituents, including salviaflaside and linolenic acid highly contained in the seed and phenolic acids, flavonoids, and triterpenoid saponins in the stem and leaf. In general, the constituents in the spica were composed of those in the seed, stem, and leaf. UPLC was used to determine the content of 6 phenolic acids(danshensu, protocatechuic acid, protocatechuic aldehyde, caffeic acid, salviaflaside, and rosmarinic acid) in different parts. The content of other phenolic acids in the seed was generally lower than that in the spica except that of salviaflaside. The content of salviaflaside in the spica was higher than that in the stem and leaf, but the content of other phenolic acids in the spica was not significantly different from that in the stem. The content of protocatechuic aldehyde and caffeic acid in the spica was lower than that in the leaf. DPPH free radical scavenging method was used to detect the antioxidant activity of four parts, and there was no significant difference in the antioxidant activity between the spica and the stem and leaf, but that was significantly higher than the seed. Moreover, the antioxidant activity of these parts was correlated with the content of total phenolic acids. Based on the above findings, the stem and leaf of P. vulgaris have potential application value. Considering the traditional medication rule, it is feasible to use the whole plant as a medicine. Alternatively, salviaflaside, occurring in the seed, can be used as a marker compound for the quality evaluation of Prunellae Spica, if only using spica as the medicinal part of P. vulgaris, as described in the Chinese Pharmacopoeia(2020 edition).

[New steroidal saponins from aerial parts of Paris polyphylla var. chinensis].

The shortage of Paridis Rhizoma promotes comprehensive utilization and development research of waste aerial parts of the original plant. The chemical compositions of the aerial parts of Paris polyphylla var. chinensis were clarified based on the ultrahigh performance liquid chromatography tandem quadrupoles time of flight mass spectrometry(UPLC-QTOF-MS/MS) in the previous investigation, and a series of flavonoids and steroidal saponins were isolated. The present study continued the isolation and structure identification of the new potential compounds discovered based on UPLC-QTOF-MS/MS. By using silica gel, ODS, flash rapid preparation, and other column chromatography techniques, combined with prepared high performance liquid chromatography, five compounds were isolated from the 75% ethanol extract of the aerial parts of P. polyphylla var. chinensis, and their structures were identified by spectral data combined with chemical transformations, respectively, as(23S,25R)-23,27-dihydroxy-diosgenin-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→3)]-ß-D-glucopyranoside(1),(25R)-26-O-ß-D-glucopyranosyl-furost-5-en-3ß,22α,26-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranoside(2),(25R)-27-O-ß-D-glucopyranosyl-5-en-3ß,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranoside(3),(25R)-27-O-ß-D-glucopyranosyl-5-en-3ß,27-dihydroxyspirost-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→3)]-ß-D-glucopyranoside(4), and aculeatiside A(5). Among them, compounds 1-4 were new ones, and compound 5 was isolated from P. polyphylla var. chinensis for the first time.

[Discovery, isolation and structural identification of alkaloid glycosides in six traditional Chinese medicine such as Coptis chinensis].

Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-ß-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-ß-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.

The Effects of Vitamin D on Markers of Glucose and Obesity in Postmenopausal Women: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: The effect of vitamin D effect on glucose markers and obesity in postmenopausal women remains controversial. The current literature contains little information on vitamin D dosage and duration for optimal efficacy in postmenopausal women. This meta-analysis was undertaken to assess the impact of vitamin D on glucose markers and obesity in postmenopausal women. METHODS: A number of databases were used dated up to January 5, 2023, with no language restrictions (PubMed/MEDLINE, Web of Science, EMBASE, and Scopus). Treatment response from baseline was estimated from the mean within-group analysis, and SDs were used to calculate the treatment response. FINDINGS: Nine eligible articles with 12 comparisons qualified for the final quantitative analysis. An overall decrease was noted in fasting blood glucose (weighted mean difference [WMD], -3.56 mg/dL; 95% CI, -5.49 to -1.64; P < 0.001), homeostatic model assessment for insulin resistance (WMD, -1.168 mm; 95% CI, -2.001 to -0.33; P = 0.006), insulin (WMD, -2.26 units; 95% CI, -4.35 to -0.18; P = 0.033), and glycosylated hemoglobin (WMD, -0.41%; 95% CI, -0.54 to -0.29; P < 0.001) after vitamin D administration in postmenopausal women. In subgroup analyses, a notable decrease in fasting blood glucose was detected when the intervention course was ˃6 months and dosage ≤1000 IU/d (WMD, -3.48 mg/dL). The present study showed that vitamin D was not associated with body mass index, body weight, or waist circumference in postmenopausal women. IMPLICATIONS: Vitamin D is beneficial for glucose markers but not obesity in postmenopausal women. An individualized dosage regimen of vitamin D should be followed depending on the clinical outcome target of postmenopausal women.

Saccharomyces boulardii protects against murine experimental colitis by reshaping the gut microbiome and its metabolic profile.

Introduction: Saccharomyces boulardii (S. boulardii) has shown clinical beneficial effect in inflammatory bowel diseases recently. However, the underlying mechanisms remain incompletely understood. The aim of present study was to tested whether S. boulardii targets gut microbiota to protect against the development of experimental colitis in mice. Methods: Female C57BL/6 mice were gavaged with S. boulardii for 3 weeks before being challenged with dextran sulphate sodium to induce ulcerative colitis. Bodyweight, diarrhea severity, intestinal permeability, colonic histopathology, colonic inflammatory status, and epithelial cell death of mice were examined. The fecal microbiota and its metabolomic profiles were detected by 16S rDNA sequencing and UPLC-MS, respectively. Results and Discussion: Supplementation with S. boulardii significantly prevented weight loss and colon shortening, lowered colonic inflammation, ameliorated epithelial injury, and enhanced the intestinal barrier integrity in colitis mice. By inhibiting the abundance of pathogenic bacteria and increasing the probiotics abundance, S. boulardii improved the microbial diversity and restored the microbiota dysbiosis. Moreover, it also modulated microbial metabolome and altered the relative contents of metabolites involving amino acids, lipids, energy and vitamin metabolisms. These yeast-driven shifts in gut flora and metabolites are were associated with each other and with the inflammation profile in colitis. Collectively, S. boulardii exerts protective effects on colitis in mice by reshaping gut microbiome and its metabolic profile, indicating it as a promising therapeutic avenue.