CD133 ligand-enhanced etoposide-liposome complex for targeted killing of lung cancer cells.

Lung cancer has a high incidence rate and a low cure rate, hence the urgent need for effective treatment methods. Current lung cancer drugs have several drawbacks, including low specificity, poor targeting, drug resistance, and irreversible damage to normal tissues. Therefore, there is a need to develop a safe and effective new drug that can target and kill tumor cells. In this study, we combined nanotechnology and biotechnology to develop a CD133 ligand-modified etoposide-liposome complex (Lipo@ETP-CD133) for targeted therapy of lung cancer. The CD133 ligand targeted lung cancer stem cells, causing the composite material to aggregate at the tumor site, where high levels of ETP liposomes could exert a strong tumor-killing effect. Our research results demonstrated that this nano-drug had efficient targeting and tumor-killing effects, indicating its potential for clinical application.

Differential diagnosis of Crohn's disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning.

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Leveraging new methods for comprehensive characterization of mitochondrial DNA in esophageal squamous cell carcinoma.

BACKGROUND: Mitochondria play essential roles in tumorigenesis; however, little is known about the contribution of mitochondrial DNA (mtDNA) to esophageal squamous cell carcinoma (ESCC). Whole-genome sequencing (WGS) is by far the most efficient technology to fully characterize the molecular features of mtDNA; however, due to the high redundancy and heterogeneity of mtDNA in regular WGS data, methods for mtDNA analysis are far from satisfactory. METHODS: Here, we developed a likelihood-based method dMTLV to identify low-heteroplasmic mtDNA variants. In addition, we described fNUMT, which can simultaneously detect non-reference nuclear sequences of mitochondrial origin (non-ref NUMTs) and their derived artifacts. Using these new methods, we explored the contribution of mtDNA to ESCC utilizing the multi-omics data of 663 paired tumor-normal samples. RESULTS: dMTLV outperformed the existing methods in sensitivity without sacrificing specificity. The verification using Nanopore long-read sequencing data showed that fNUMT has superior specificity and more accurate breakpoint identification than the current methods. Leveraging the new method, we identified a significant association between the ESCC overall survival and the ratio of mtDNA copy number of paired tumor-normal samples, which could be potentially explained by the differential expression of genes enriched in pathways related to metabolism, DNA damage repair, and cell cycle checkpoint. Additionally, we observed that the expression of CBWD1 was downregulated by the non-ref NUMTs inserted into its intron region, which might provide precursor conditions for the tumor cells to adapt to a hypoxic environment. Moreover, we identified a strong positive relationship between the number of mtDNA truncating mutations and the contribution of signatures linked to tumorigenesis and treatment response. CONCLUSIONS: Our new frameworks promote the characterization of mtDNA features, which enables the elucidation of the landscapes and roles of mtDNA in ESCC essential for extending the current understanding of ESCC etiology. dMTLV and fNUMT are freely available from https://github.com/sunnyzxh/dMTLV and https://github.com/sunnyzxh/fNUMT , respectively.

Linoelaidic acid gavage has more severe consequences on triglycerides accumulation, inflammation and intestinal microbiota in mice than elaidic acid.

This work aims to study the effects of oral gavage (0.2 mg/g body weight) of elaidic acid (C18:1-9 t, EA) and linoelaidic acid (C18:2-9 t,12 t, LEA) on lipid metabolism, inflammation and gut homeostasis of mice. Results showed that both EA and LEA gavage significantly increased LDL-c, TC and oxidative stress levels in the liver and serum and may stimulate liver inflammation via NF-κB and MAPK signaling pathway. Compared with EA, LEA gavage significantly promoted TAG accumulation and inflammatory signaling. Serum lipidomics revealed that LEA intake significantly increased the concentration of ∼50 TAGs, while EA gavage primarily caused significant decreases in several SMs. 16S rRNA demonstrated that LEA ingestion markedly changed fecal microbiota by enriching Lactobacillus (phylum Firmicutes), however, EA treatment did not affect it. Overall, LEA gavage has more severe consequences on TAG accumulation, inflammation and microbial structure than EA, highlighting that the number of trans double bonds affects these processes.

Pararorine A, isoindolinone alkaloid from the endophytic fungus Paramyrothecium roridum and its anti-tumor activity.

Pararorine A, a new isoindolinone alkaloid was isolated from Paramyrothecium roridum, an endophytic fungus from the medicinal plant Gynochthodes officinalis (F.C. How) Razafim. & B. Bremer. The structure of this compound was elucidated by extensive spectroscopic (UV, IR, MS, and NMR) analyses. In addition, the antitumor activity of pararorine A was evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that pararorine A exhibited potent antitumor activities with the IC50 values ranging from 1.69 to 8.95 µM. Moreover, the tumor cell inhibitory activity of pararorine A was evidenced by promoting cytochrome C release and cell cycle arrest as well as the induction of apoptosis by the up-regulation of the protein expressions of JNK and Bax through PARP-cleavage and caspase 3-cleavage.

Irpexols A-C, xanthone derivatives from the endophyte fungus Irpex laceratus A878.

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses includingultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly­oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC50 values ranging from 24.83 to 45.46 µM, while the IC50 values of the positive control adriamycin was ranging from 1.11 to 1.44 µM.

Salvia miltiorrhiza ameliorates endometritis in dairy cows by relieving inflammation, energy deficiency and blood stasis.

Introduction: According to traditional Chinese veterinary medicine, endometritis is caused by a combination of Qi deficiency, blood stasis, and external evil invasion. Salvia miltiorrhiza is a traditional Chinese medicine that counteracts blood stasis and has additional demonstrated effects in boosting energy and restraining inflammation. Salvia miltiorrhiza has been employed in many traditional Chinese prescriptions that have proven effective in healing clinical dairy cow endometritis. Methods: the in vivo effect of Salvia miltiorrhiza in treating endometritis was evaluated in dairy cows. In addition, bovine endometrial epithelium cell inflammation and rat blood stasis models were employed to demonstrate the crosstalk between energy, blood circulation and inflammation. Network analysis, western blotting, qRT-PCR and ELISA were performed to investigate the molecular mechanism of Salvia miltiorrhiza in endometritis treatment. Results: The results demonstrate that treatment with Salvia miltiorrhiza relieves uterine inflammation, increases blood ATP concentrations, and prolongs blood clotting times. Four of the six Salvia miltiorrhiza main components (SMMCs) (tanshinone IIA, cryptotanshinone, salvianolic acid A and salvianolic acid B) were effective in reversing decreased ATP and increased IL-1ß, IL-6, and IL-8 levels in an in vitro endometritis model, indicating their abilities to ameliorate the negative energy balance and external evil invasion effects of endometritis. Furthermore, in a blood stasis rat model, inflammatory responses were induced in the absence of external infection; and all six SMMCs inhibited thrombin-induced platelet aggregation. Network analysis of SMMC targets predicted that Salvia miltiorrhiza may mediate anti-inflammation via the Toll-like receptor signaling pathway; anti-aggregation via the Platelet activation pathway; and energy balance via the Thermogenesis and AMPK signaling pathways. Multiple molecular targets within these pathways were verified to be inhibited by SMMCs, including P38/ERK-AP1, a key molecular signal that may mediate the crosstalk between inflammation, energy deficiency and blood stasis. Conclusion: These results provide mechanistic understanding of the therapeutic effect of Salvia miltiorrhiza for endometritis achieved through Qi deficiency, blood stasis, and external evil invasion.

Li Promoting Long Afterglow Organic Light-Emitting Transistor for Memory Optocoupler Module.

The artificial brain is conceived as advanced intelligence technology, capable to emulate in-memory processes occurring in the human brain by integrating synaptic devices. Within this context, improving the functionality of synaptic transistors to increase information processing density in neuromorphic chips is a major challenge in this field. In this article, Li-ion migration promoting long afterglow organic light-emitting transistors, which display exceptional postsynaptic brightness of 7000 cd m-2 under low operational voltages of 10 V is presented. The postsynaptic current of 0.1 mA operating as a built-in threshold switch is implemented as a firing point in these devices. The setting-condition-triggered long afterglow is employed to drive the photoisomerization process of photochromic molecules that mimic neurotransmitter transfer in the human brain for realizing a key memory rule, that is, the transition from long-term memory to permanent memory. The combination of setting-condition-triggered long afterglow with photodiode amplifiers is also processed to emulate the human responding action after the setting-training process. Overall, the successful integration in neuromorphic computing comprising stimulus judgment, photon emission, transition, and encoding,  to emulate the complicated decision tree of the human brain is demonstrated.

TfR1 mediated iron metabolism dysfunction as a potential therapeutic target for osteoarthritis.

OBJECTIVE: Transferrin receptor-1 (TfR1) plays important roles in controlling cellular iron levels, but its role in OA pathology is unknown. Herein we aim to investigate the role of TfR1 in OA progression and its underlying mechanisms. METHODS: TfR1 expression in cartilage during OA development were examined both in vivo and in vitro. Then IL-1ß was used to induce chondrocytes degeneration in vitro and TfR1 siRNA was used for observing the effect of TfR1 in modulating iron homeostasis, mitochondrial function and degrading enzymes expression. Also the inhibitor of TfR1 was exploited to analyze the protective effect of TfR1 inhibition in vivo. RESULTS: TfR1 is elevated in OA cartilage and contributes to OA inflammation condition. Excess iron not only results in oxidative stress damage and sensitizes chondrocytes to ferroptosis, but also triggers c-GAS/STING-mediated inflammation by promoting mitochondrial destruction and the release of mtDNA. Silencing TfR1 using TfR1 siRNA not only reduced iron content in chondrocytes and inhibited oxidative stress, but also facilitated the mitophagy process and suppressed mtDNA/cGAS/STING-mediated inflammation. Importantly, we also found that Ferstatin II, a novel and selective TfR1 inhibitor, could substantially suppress TfR1 activity both in vivo and in vitro and ameliorated cartilage degeneration. CONCLUSION: Our work demonstrates that TfR1 mediated iron influx plays important roles in chondrocytes degeneration and OA pathogenesis, suggesting that maintaining iron homeostasis through the targeting of TfR1 may represent a novel therapeutic strategy for the treatment of OA.

Correlation analysis and clinical significance of changes in upper thoracic vertebra tilt and clavicle angle pre- and post-operation.

The imbalance of the lateral shoulder is reflected by the clavicle angle (CA) in radiology. It remains unclear how to achieve postoperative lateral shoulder balance (LSB) after spinal deformity correction surgery. A retrospective analysis was conducted on AIS patients who underwent surgery by the same spine surgeon at our hospital from 2016 to 2020. A total of 110 patients with spinal deformity were included in the study to verify the correlation between the T1-T5 tilt angle and CA before and after surgery, as well as the relation-ship between the change in T1-T5 tilt angle before and after surgery and the change in CA before and after surgery. By comparing the correlation coefficients, it was found that there may not be a direct relationship between the pre- and postoperative tilt angles of T1-5 and CA, but their changes were closely related to the changes in CA. The change in T1 tilt angle after orthopaedic surgery was significantly correlated with the change in CA, with a correlation coefficient of 0.976, indicating a close relationship between T1 and the clavicle. As the vertebrae moved down, the correlation gradually decreased. In summary, this study suggests that there is a close relationship between T1-T5 and the clavicle and that the change in T1 tilt angle after spinal scoliosis correction surgery is significantly correlated with CA, which decreases as the vertebra moves down.

The role of fat content in coconut milk: Stability and digestive properties.

The fat in coconut milk contributes to unique flavour, while increasing fat content affects stability of the coconut milk. In this study, coconut water and fat were separated, recombined, and homogenized to obtain coconut milk with different fat contents (0-20 %). Emulsifying properties, stability, and digestibility of coconut milk with different fat contents were comprehensively evaluated. The results showed that as the fat content increased from 0 to 20 %, the droplet size increased from 2.18 to 4.70 µm and the viscosity showed an increasing trend. During storage and freeze-thaw, coconut milk with 5 % and 10 % fat content showed excellent stability. In addition, coconut milk with 10 % fat content had superior fat digestibility, which was related to high affinity of pancrelipase. In short, this study revealed that fat content below 10 % can withstand environmental factors such as storage, lipid oxidation, and freeze-thaw, which can be accurately developed as coconut milk products.

Bovine serum albumin-liposome stabilized high oil-phase emulsion: Effect of liposome ratio on interface properties and stability.

This study aimed to solve the issue of poor lipophilicity of natural bovine serum albumin (BSA) by combining with liposomes (Lips) to stabilize high oil-phase emulsions (HOPEs). The interaction between BSA and Lips was mainly driven by hydrophobic forces, followed by hydrogen bonding. The secondary structure and tertiary structure of BSA were characterized and indicated that the addition of Lips promoted the structural expansion of BSA exposing the hydrophobic groups inside. Interfacial adsorption behaviours were assessed through dynamic interfacial tension, three-phase contact angle, and quartz crystal microbalance with dissipation. These results indicated that BSA-Lips crosslinking improved wettability, promoting adsorption and rearrangement at the oil-water interface, thereby resulting in a dense interfacial layer. The emulsifying efficacy of BSA-stabilized HOPEs also displayed a distinct Lips dependency. Varying the BSA-to-Lips ratio transformed their consistency from flowing to semi-solid, reinforcing the gel network. Under optimal conditions (BSA: Lips = 1:1), the droplet size of BSA-Lips stabilized HOPEs reached a minimum with a highly uniform distribution. Moreover, a 1:1 BSA to Lips ensured outstanding storage, thermal, and centrifugal stability for the HOPEs. This work provides valuable references for the interaction between protein and Lips, guiding the development of highly stable HOPEs stabilizers.

The effect of Bletilla striata polysaccharide on the physical and healing properties of curdlan-based hydrogel for wound healing.

Bletilla striata polysaccharide (BSP) was added to curdlan to form a blend hydrogel through a simple heating-cooling procedure to improve the hydrophilicity and healing efficacy of curdlan-based hydrogel used in wound healing. We explored the interplay between BSP and curdlan, studied how BSP concentration affects the physical properties and microstructures of hydrogels, and examined the biocompatibility and healing properties of the blend hydrogel. It was proved that the hydrogel framework was primarily formed by ordered arranged curdlan molecules, with BSP uniformly dispersed and intertwined with curdlan through hydrogen bonding. This effectively improved its hydrophilicity and strengthened the microstructure. Curdlan was found to be compatible with BSP. The blend hydrogel B3Cd3 (containing 1.5% BSP and 1.5% curdlan, w/v) was identified as the optimal formulation based on its higher water adsorption, water retention, thermal stability and interconnected microstructure, and was thus selected for further research. In vitro experiments revealed the highest cell viability of L929 in B3Cd3 extracts compared to those extracts of single-component curdlan hydrogel (Cd). In vivo, animal studies indicated that the B3Cd3 accelerated wound healing compared to the control group by improving re-epithelialization and blood vessel regeneration. On Days 3 and 11, the therapeutic benefits of B3Cd3 exceeded those of the Cd group, and no significant differences were observed in wound healing rates between the B and B3Cd3 groups from Day 7. The study proves that BSP enhances the physical and healing properties, as well as cell proliferation, of the curdlan-based hydrogel. The blend hydrogel B3Cd3, with its exceptional properties, holds potential for future application as a material for non-infected wound healing.

Effect of miR-17 on Polygonum Cillinerve polysaccharide against transmissible gastroenteritis virus.

Transmissible gastroenteritis virus (TGEV) could cause diarrhea, vomiting, dehydration and even death in piglets, miRNA played an important role in the interaction between virus and cell. The study aimed to investigate the impact of miR-17 on the polysaccharide of Polygonum Cillinerve (PCP) in combating TGEV. miR-17 was screened and transfection validation was performed by Real-time PCR. The function of miR-17 on PK15 cells infected with TGEV and treated with PCP was investigated by DCFH-DA loading probe, JC-1 staining and Hoechst fluorescence staining. Furthermore, the effect of miR-17 on PCP inhibiting TGEV replication and apoptosis signaling pathways during PCP against TGEV infection was measured through Real-time PCR and Western blot. The results showed that miR-17 mimic and inhibitor could be transferred into PK15 cells and the expression of miR-17 significantly increased and decreased respectively compared with miR-17 mimic and inhibitor (P < 0.05). A total 250 µg/mL of PCP could inhibit cells apoptosis after transfection with miR-17. PCP (250 µg/mL and 125 µg/mL) significantly inhibited the decrease in mitochondrial membrane potential induced by TGEV after transfection with miR-17 (P < 0.05). After transfection of miR-17 mimic, PCP at concentrations of 250 µg/mL and 125 µg/mL significantly promoted the mRNA expression of P53, cyt C and caspase 9 (P < 0.05). Compared with the control group, the replication of TGEV gRNA and gene N was significantly inhibited by PCP at concentrations of 250 µg/mL and 125 µg/mL after transfection of both miR-17 mimic and inhibitor (P < 0.05). PCP at 62.5 µg/mL significantly inhibited the replication of gene S following transfection with miR-17 inhibitor (P < 0.05). These results suggested that PCP could inhibit the replication of TGEV and apoptosis induced by TGEV by regulating miR-17.

Sequence variations in GATA4 and CITED2 gene among patients with cardiac septation defects from Xinjiang, China.

Studies have shown that genetic factors play an important role in CHD's development. The mutations in GATA4 and CITED2 genes result in the failure of the heart to develop normally, thereby leading to septal defects. The present study investigated the underlying molecular aetiology of patients with cardiac septation defects from Xinjiang. We investigated variants of the GATA4 and CITED2 gene coding regions in 172 patients with cardiac septation defects by sequencing. Healthy controls (n = 200) were included. Three heterozygous variations (p.V380M, p.P394T, and p.P407Q) of the GATA4 gene were identified in three patients. p.V380M was discovered in a patient with atrial septal defect. p.P394T was noted in a patient with atrial septal defect. p.V380M and p.P407Q of the GATA4 gene were detected in one patient with ventricular septal defect. A novel homozygous variation (p. Sl92G) of the CITED2 gene was found in one patient with ventricular septal defect. Other patients and healthy individuals were normal. The limited prevalence of genetic variations observed in individuals with cardiac septal defects from Xinjiang provides evidence in favour of the hypothesis that CHD is a polygenic hereditary disorder. It is plausible that mutations in the GATA4 and CITED2 genes could potentially underlie the occurrence of idiopathic CHD in affected patients.

Structural characteristics and stability analysis of coconut oil body and its application for loading ß-carotene.

In this work, we investigated structural characteristics and stability analysis of the coconut oil body (COB) and its application for loading ß-carotene (ß-CA). The COB contained neutral lipids (81.1 ± 2.1 %), membrane proteins (0.6 ± 0.0 %), and moistures (18.3 ± 3.2 %), in which the molecular weights of membrane proteins ranged from 12 kDa to 40 kDa, as analyzed by the SDS-PAGE. The COB exhibited a small droplet diameter (5.1 ± 0.3 µm) with a monomodal diameter distribution, as reflected by the dynamic light scattering. The COB showed stable states at alkaline pH values (pH 8-10) and instability against ionic strengths (50-200 mmol/L) and thermal treatment (30-90℃) after analyzing the instability indexes. COB-based emulsions were favorable for the loading and retention of ß-CA, as reflected by free fatty acids release rates and bioaccessibility in the simulated gastrointestinal digestion. This study will contribute to using the coconut oil bodies for loading bioactive nutraceuticals to enhance their bioaccessibility.

Polygonum cillinerve polysaccharide inhibits transmissible gastroenteritis virus by regulating microRNA-181.

Transmissible gastroenteritis virus (TGEV) is an important pathogen capable of altering the expression profile of cellular miRNA. In this study, the potential of Polygonum cillinerve polysaccharide (PCP) to treat TGEV-infected piglets was evaluated through in vivo experiments. High-throughput sequencing technology was employed to identify 9 up-regulated and 17 down-regulated miRNAs during PCP-mediated inhibition of TGEV infection in PK15 cells. Additionally, miR-181 was found to be associated with target genes of key proteins in the apoptosis pathway. PK15 cells were treated with various concentrations of PCP following transfection with miR-181 mimic or inhibitor. Real-time PCR assessed the impact on TGEV replication, while electron microscopy (TEM) and Hoechst fluorescence staining evaluated cellular functionality. Western blot analysis was utilized to assess the expression of key signaling factors-cytochrome C (cyt C), caspase 9, and P53-in the apoptotic signaling pathway. The results showed that compared with the control group, 250 µg/mL PCP significantly inhibited TGEV gRNA replication and gene N expression (P < 0.01). Microscopic examination revealed uniform cell morphology and fewer floating cells in PCP-treated groups (250 and 125 µg/mL). TEM analysis showed no typical virus structure in the 250 µg/mL PCP group, and apoptosis staining indicated a significant reduction in apoptotic cells at this concentration. Furthermore, PCP may inhibit TGEV-induced apoptosis via the Caspase-dependent mitochondrial pathway following miR-181 transfection. These findings provide a theoretical basis for further exploration into the mechanism of PCP's anti-TGEV properties.

On the genetic basis of tail-loss evolution in humans and apes.

The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes'1-3, with a proposed role in contributing to human bipedalism4-6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene7-9-pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans10. Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.

Effect of different acupuncture sequences of Huiyangjiuzhen acupoints on blood glucose and hemorheology in the anesthetized rabbits.

Background and objective: Hemorheology and blood glucose are commonly used to estimate the risks of thrombosis and stress hyperglycemia after anaesthesia. The sequence of acupoint stimulation might influence the therapeutic effects of acupuncture. In the current study, we aimed at investigating the effect of different acupuncture sequences of "Huiyangjiuzhen" acupoints on the blood glucose and hemorheology in anesthetized rabbits. Methods: Twenty-five rabbits were randomly divided into five groups, including the control group (CG), the positive-sequence group (PSG), the reverse-sequence group (RSG), the disorder-sequence group (DSG), and the random group (RG). Except for the CG and RG, the rabbits in other groups were acupunctured with different sequences of "Huiyangjiuzhen"acupoints when the rabbits were anesthetized. The acupoints in rabbits of the RG were chosen randomly. The levels of blood glucose and hemorheology indexes before and after anaesthesia was detected. Results: In the PSG, Hηb 200/s, Mηb 30/s, Hηr 200/s, ERI, hematocrit and plasma viscosity levels were decreased, and the blood glucose level was not changed. In the DSG, the levels of Mηb 30/s and hematocrit were decreased, and the blood glucose was increased. In the CG, RSG and RG, no hemorheology indexes were changed and the blood glucose was increased. Conclusion: "Huiyangjiuzhen" acupuncture could decrease the risks of post-operative thrombosis and stress hyperglycemia in anesthetized rabbits. This effectiveness depends on both acupuncture and acupuncture sequence at the "Huiyangjiuzhen" acupoints.

Expanding the Chemical Diversity of Grisechelins via Heterologous Expression.

Thiazole scaffold-based small molecules exhibit a range of biological activities and play important roles in drug discovery. Based on bioinformatics analysis, a putative biosynthetic gene cluster (BGC) for thiazole-containing compounds was identified from Streptomyces sp. SCSIO 40020. Heterologous expression of this BGC led to the production of eight new thiazole-containing compounds, grisechelins E, F, and I-N (1, 2, 5-10), and two quinoline derivatives, grisechelins G and H (3 and 4). The structures of 1-10, including their absolute configurations, were elucidated by HRESIMS, NMR spectroscopic data, ECD calculations, and single-crystal X-ray diffraction analysis. Grisechelin F (2) is a unique derivative, distinguished by the presence of a salicylic acid moiety. The biosynthetic pathway for 2 was proposed based on bioinformatics analysis and in vivo gene knockout experiments. Grisechelin E (1) displayed moderate antimycobacterial activity against Mycobacterium tuberculosis H37Ra (MIC of 8 µg mL-1).