[Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative].

The protection, development, and utilization of medicinal plant resources are important cornerstones of maintaining human health. However, due to factors such as the reduction of high-quality land resources, deterioration of ecological environments, and excessive and disorderly resource development, medicinal plant resources are becoming scarce, and some of them are insufficiently supplied. With the proposal of "the Belt and Road" Initiative, the cooperation between China and "the Belt and Road" partners(the countries and regions involved in "the Belt and Road" Initiative)is increasingly close, which provides a new opportunity for carrying out trade of medicinal plant resources and alleviating the problem of imbalance and relative inadequacy of medicinal plant resources in countries. This study first determined the distribution and species information of plant resources in countries and regions involved in "the Belt and Road" Initiative by investigating the database of plant distribution and that of medicinal plant resources. Then, according to the published data from the International Union for Conservation of Nature(IUCN) and the Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), this study identified the rare and endangered medicinal plants and the medicinal plants under trade control in countries and regions involved in "the Belt and Road" Initiative and finally sorted out the list of potential medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative that can be used by China. This data resource can not only be used for the overall protection of important endangered species but also scientifically guide the development and utilization of medicinal resources, providing guidance and a theoretical basis for the sustainable development of medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative.

Human UDP-glucuronosyltransferase 1As catalyze aristolochic acid D O-glucuronidation to form a lesser nephrotoxic glucuronide.

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochic acids (AAs) are naturally occurring nitro phenanthrene carboxylic acids primarily found in plants of the Aristolochiaceae family. Aristolochic acid D (AAD) is a major constituent in the roots and rhizomes of the Chinese herb Xixin (the roots and rhizomes of Asarum heterotropoides F. Schmidt), which is a key material for preparing a suite of marketed Chinese medicines. Structurally, AAD is nearly identical to the nephrotoxic aristolochic acid I (AAI), with an additional phenolic group at the C-6 site. Although the nephrotoxicity and metabolic pathways of AAI have been well-investigated, the metabolic pathway(s) of AAD in humans and the influence of AAD metabolism on its nephrotoxicity has not been investigated yet. AIM OF THE STUDY: To identify the major metabolites of AAD in human tissues and to characterize AAD O-glucuronidation kinetics in different enzyme sources, as well as to explore the influence of AAD O-glucuronidation on its nephrotoxicity. MATERIALS AND METHODS: The O-glucuronide of AAD was biosynthesized and its chemical structure was fully characterized by both 1H-NMR and 13C-NMR. Reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses were conducted to assess the crucial enzymes involved in AAD O-glucuronidation in humans. Docking simulations were performed to mimic the catalytic conformations of AAD in human UDP-glucuronosyltransferases (UGTs), while the predicted binding energies and distances between the deprotonated C-6 phenolic group of AAD and the glucuronyl moiety of UDPGA in each tested human UGT isoenzyme were measured. The mitochondrial membrane potentials (MMP) and reactive oxygen species (ROS) levels in HK-2 cells treated with either AAI, or AAD, or AAD O-glucuronide were tested, to elucidate the impact of O-glucuronidation on the nephrotoxicity of AAD. RESULTS: AAD could be rapidly metabolized in human liver and intestinal microsomes (HLM and HIM, respectively) to form a mono-glucuronide, which was purified and fully characterized as AAD-6-O-ß-D-glucuronide (AADG) by NMR. UGT1A1 was the predominant enzyme responsible for AAD-6-O-glucuronidation, while UGT1A9 contributed to a lesser extent. AAD-6-O-glucuronidation in HLM, HIM, UGT1A1 and UGT1A9 followed Michaelis-Menten kinetics, with the Km values of 4.27 µM, 9.05 µM, 3.87 µM, and 7.00 µM, respectively. Docking simulations suggested that AAD was accessible to the catalytic cavity of UGT1A1 or UGT1A9 and formed catalytic conformations. Further investigations showed that both AAI and AAD could trigger the elevated intracellular ROS levels and induce mitochondrial dysfunction and in HK-2 cells, but AADG was hardly to trigger ROS accumulation and mitochondrial dysfunction. CONCLUSION: Collectively, UGT1A-catalyzed AAD 6-O-glucuronidation represents a crucial detoxification pathway of this naturally occurring AAI analogs in humans, which is very different from that of AAI.

Determination of the total antioxidant capacity of the Chinese tea based on a novel "peroxidase/zirconium phosphonate"composite electrochemical sensor.

In this work, a novel zirconium phosphonate (ZrPR1R2) was prepared by decorating both the aminoethoxy- group (R1) and the carboxypropyl- group (R2) on the zirconium phosphate layers in order to manipulate further the immobilization of the peroxidase (POD), and an antioxidant biosensor with higher sensitivity was constructed by dropping the POD/ZrPR1R2 composite onto the glassy carbon electrode surface. The activity of the POD/ZrPR1R2 composite was detected by Uv-vis spectra. The direct electrochemical behavior, the electrocatalytic response to dissolved oxygen and hydrogen peroxide, as well as the ability to detect total antioxidant capacity in tea sample were investigated by the methods of cyclic voltammetry. The results indicated that the immobilization of POD in ZrPR1R2 nanosheets matrix enhanced the enzymatic activity, and achieved the fast and direct electron transfer between POD and glassy carbon electrode. Moreover, the POD/ZrPR1R2 composite modified electrode show the electrocatalytic response to hydrogen peroxide in the linear range of 8.8×10-8 to 8.8×10-7 mol L-1, with the detection limit of 3.3×10-8 mol L-1. Attributing to the sensitive response to dissolved oxygen, the total antioxidant capacity can be detected directly in the real tea water by this POD/ZrPR1R2 composite modified electrode.

Long-term survival in patients with PMP: a single-institutional retrospective study from China.

BACKGROUND: As the standard treatment for pseudomyxoma peritonei (PMP), cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) can significantly prolong the survival of PMP patients, and some patients can even achieve long-term survival (LTS) or clinical cure. The purpose of this study was to analyze the clinicopathological and treatment features of PMP patients with LTS and to explore the survival benefit factors of PMP patients. METHODS: The clinicopathological and prognostic data of PMP patients who received CRS + HIPEC at our center from December 2004 to May 2023 were retrospectively analyzed. PMP patients were divided into LTS group (≥ 10 years) and short-term survival (STS) group (< 5 years) according to the length of natural history. Univariate and multivariate analyses were performed to explore the beneficial factors of PMP patients with LTS. RESULTS: A total of 609 patients with PMP received CRS + HIPEC treatment at our center. Two-hundred one patients with PMP were included in the study after screening, including 39 patients (19.4%) in the LTS group and 162 patients (80.6%) in the STS group. In STS group and LTS group, median overall survival based on natural history was 29.2 (2.4-59.9) vs. 138.9 (120.3-416.7) months. Univariate analysis revealed 8 factors (P < 0.05) with statistically significant differences between the two groups: gender, chemotherapy history, previous surgical score, Karnofsky Performance Status score, pathological diagnosis, lymphatic metastasis, peritoneal cancer index, and completeness of cytoreduction (CC). Multivariate analysis identified only two factors independently associated with LTS of PMP patients: CC and pathological diagnosis. CONCLUSION: Complete CRS and pathological features are two key factors affecting LTS in PMP patients.

Effect of hyperthermia on intestinal microecology, immune function, and progression-free survival in patients with advanced unresectable lung adenocarcinoma.

This study aims to investigate the effects of hyperthermia on intestinal microecology, immune function, and progression-free survival of patients with advanced unresectable lung adenocarcinoma. A total of twenty patients with lung adenocarcinoma in the study group received the advanced standard first-line treatment protocol, which included pemetrexed + cisplatin combined with sintilimab immunotherapy and hyperthermia. Additionally, twenty patients with lung adenocarcinoma in the control group received the advanced standard first-line treatment protocol, which included pemetrexed + cisplatin combined with sintilimab immunotherapy. The T-lymphocyte subpopulation and CD4/CD8 cell ratio of each sample were detected using flow cytometry. The intestinal flora was evaluated using 16S rRNA gene sequencing. The study observed the changes in the abundance, distribution, composition, and structure of fecal gut microorganisms before and after the treatment in both groups of patients. Significant differences were observed in the intestinal flora between the two groups. The patients in the study group showed improved immunity after treatment, whereas there was no significant change in the immunity of the control group before and after treatment. However, the difference in progression-free survival between the two groups was not statistically significant. Hyperthermia has a significant impact on improving the microecology of intestinal flora and the immunity of patients, but it does not have a significant effect on prolonging the progression-free survival of patients.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

[Effects of catgut embedding and PGLA embedding at "Zusanli" (ST 36) on skin mast cells, substance P and histamine in healthy rats].

OBJECTIVE: To observe the effects of catgut embedding and polyglycolic acid/poly-lactic acid (PGLA) embedding at "Zusanli" (ST 36) on the activation of local skin mast cells (MC), and expression of substance P (SP) and histamine (HA), and to explore the mechanism of the temporal stimulation effect of acupoint catgut embedding and provide a foundation for further research on the initiation mechanism of acupoint catgut embedding. METHODS: One hundred and sixty male SPF-grade SD rats were randomly divided into a blank group (10 rats), a sham-embedding group (50 rats), a catgut group (50 rats), and a PGLA group (50 rats). Each intervention group was further randomly divided into five subgroups according to the time points after intervention: 8 hours, 3 days, 7 days, 14 days, and 21 days, with 10 rats in each subgroup. One-time sham-embedding, catgut embedding and PGLA embedding was given at left "Zusanli" (ST 36) in each intervention group, respectively. The skin and subcutaneous connective tissue of the left "Zusanli" (ST 36) were collected at the corresponding time points after intervention, except for the blank group (only one day before intervention). Toluidine blue staining was used to detect MC count and degranulation, and immunohistochemical staining was used to detect the expression of SP and HA positive cells. RESULTS: There was no significant difference in MC count between the subgroups of each intervention group and the blank group (P>0.05). There was no significant difference in MC count between the subgroups of the catgut group and the PGLA group (P>0.05). The MC count in the 8-hour subgroup of PGLA group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the MC count in the 21-day subgroup of PGLA group was lower than that in the 21-day subgroup of catgut group (P<0.05). Compared with the blank group, the degranulation rates of MC were increased in the 8-hour and 3-day subgroups of sham-embedding group, 8-hour, 3-day, and 7-day subgroups of catgut group, and 8-hour, 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.01, P<0.05, P<0.001). There was no significant difference in the degranulation rate of MC between the subgroups of the catgut group and the PGLA group (P>0.05), and no significant difference in the degranulation rate of MC between the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of SP positive cells was increased in the 8-hour subgroup of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.001, P<0.05). The expression of SP positive cells in the 7-day subgroup of catgut group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.001). The expression of SP positive cells in the 7-day subgroup of PGLA group was higher than that in the 3-day subgroup of PGLA group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.01). There was no significant difference in the expression of SP positive cells between the subgroups of the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of HA positive cells was increased in the 8-hour, 3-day subgroups of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 8-hour, 3-day, 7-day, 14-day, and 21-day subgroups of PGLA group (P<0.001, P<0.01, P<0.05). The expression of HA positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.05), while the expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 8-hour subgroup of PGLA group (P<0.05), and the expression of HA positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.05). The expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 3-day subgroup of catgut group (P<0.05). CONCLUSION: Catgut and PGLA embedding at "Zusanli" (ST 36) in healthy rats could induce changes in local skin MC, SP, and HA, which may be one of the mechanisms of the temporal stimulation effect after acupoint embedding. There are certain differences between different suture materials. A moderate inflammatory response in the acupoint area, mediated by MC and involving SP and HA, may be one of the initiating factors for the effect of acupoint catgut embedding.

[Effect of catgut implantation on macrophage CD68, tumor necrosis factor-α and interleukin-1ß in "Zusanli" (ST 36) region of rats].

OBJECTIVE: To observe the expression of local macrophages and related cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) after catgut implantation in "Zusanli"(ST 36) in rats, so as to explore its underlying mechanisms in inducing therapeutic effect. METHODS: A total of 110 male SD rats were randomly divided into blank control group (n=10), catgut embedding (CE) group (n=50), and sham CE group (n=50). The CE and sham CE groups were randomly divided into 8 h, 3 d, 7 d, 14 d and 21 d subgroups after the intervention (n=10 in each time point group). Rats of the CE group were uniformly subjected into catgut embedding at ST36 once, and those of the sham CE group received embedding needle puncture at ST36 without catgut retention, and the blank control group was only grasped and fixed without other treatments. Tissues from the ST36 area in each group were collected at the corresponding time points, and the expression of CD68 in macrophages in the acupoint area was detected by immunofluorescence, the contents of TNF-α and IL-1ß in the acupoint area were detected by ELISA. RESULTS: Following catgut embedment at ST36, the contents of TNF-α and IL-1ß, and macrophage CD68 expression level began to increase at 8 h, peaked at 3 d, and then gradually decreased at 7, 14, and 21 d, being still higher in the CE group than in the blank control group at 21 d (P<0.05). Compared with the blank control group, the contents of TNF-α and IL-1ß, and macrophage CD68 expression were significantly increased at 8 h, and 3, 7, 14 and 21 d in the CE group (P<0.05). Following sham CE at ST36, the content of TNF-α at 8 h and 3 d, IL-1ß at 8 h and 3, 7 and 14 d, and expression of CD68 at 8 h were significantly increased in comparison with the blank control group (P<0.05). Comparison between the CE and sham CE groups showed that the contents of IL-1ß at 3, 7, 14 and 21 d, and contents of TNF-α，CD68 expression at 8 h, and 3, 7, 14 and 21 d were significantly higher in the CE group than in the sham CE group (P<0.05). CONCLUSION: Catgut embedding at ST36 can induce an increase levels of inflammatory cytokines TNF-α, IL-1ß and macrophage CD68 in the local microenvironment in rats, which may contribute to its functions in initiating therapeutic effect.

Establishment of a Bayesian network model to predict the survival of malignant peritoneal mesothelioma patients after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

OBJECTIVES: To establish a Bayesian network (BN) model to predict the survival of patients with malignant peritoneal mesothelioma (MPM) treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: The clinicopathological data of 154 MPM patients treated with CRS + HIPEC at our hospital from April 2015 to November 2022 were retrospectively analyzed. They were randomly divided into two groups in a 7:3 ratio. Survival analysis was conducted on the training set and a BN model was established. The accuracy of the model was validated using a confusion matrix of the testing set. The receiver operating characteristic (ROC) curve and area under the curve were used to evaluate the overall performance of the BN model. RESULTS: Survival analysis of 107 patients (69.5%) in the training set found ten factors affecting patient prognosis: age, Karnofsky performance score, surgical history, ascites volume, peritoneal cancer index, organ resections, red blood cell transfusion, pathological types, lymphatic metastasis, and Ki-67 index (all p < 0.05). The BN model was successfully established after the above factors were included, and the BN model structure was adjusted according to previous research and clinical experience. The results of confusion matrix obtained by internal validation of 47 cases in the testing set showed that the accuracy of BN model was 72.7%, and the area under ROC was 0.74. CONCLUSIONS: The BN model was established successfully with good overall performance and can be used as a clinical decision reference.

[Monoterpenoids from Paeoniae Radix Rubra based on UPLC-Q-TOF-MS].

The ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to conduct the qualitative analysis of the monoterpene chemical components from Paeoniae Radix Rubra. Gradient elution was performed on C_(18) HD(2.1 mm×100 mm, 2.5 µm) column with a mobile phase of 0.1% formic acid(A) and acetonitrile(B). The flow rate was 0.4 mL·min~(-1) and the column temperature was 30 ℃. MS analysis was conducted in both positive and negative ionization modes using electrospray ionization(ESI) source. Qualitative Analysis 10.0 was used for data processing. The identification of chemical components was realized by the combination of standard compounds, fragmentation patterns, and mass spectra data reported in the literature. Forty-one monoterpenoids in Paeoniae Radix Rubra extract were identified. Among them, 8 compounds were reported in Paeoniae Radix Rubra for the first time and 1 was presumed to be the new compound 5″-O-methyl-galloylpaeoniflorin or its positional isomer. The method in this study realizes the rapid identification of monoterpenoids from Paeoniae Radix Rubra and provides a material and scientific basis for quality control and further study on the pharmaceutical effect of Paeoniae Radix Rubra.

RHO OF PLANT proteins are essential for pollen germination in Arabidopsis.

Pollen germination is a process of polarity establishment, through which a single and unique growth axis is established. Although most of the intracellular activities associated with pollen germination are controlled by RHO OF PLANTs (ROPs) and increased ROP activation accompanies pollen germination, a critical role of ROPs in this process has not yet been demonstrated. Here, by genomic editing of all 4 Arabidopsis (Arabidopsis thaliana) ROPs that are preferentially expressed in pollen, we showed that ROPs are essential for polarity establishment during pollen germination. We further identified and characterized 2 ROP effectors in pollen germination (REGs) through genome-wide interactor screening, boundary of ROP domain (BDR) members BDR8 and BDR9, whose functional loss also resulted in no pollen germination. BDR8 and BDR9 were distributed in the cytosol and the vegetative nucleus of mature pollen grains but redistributed to the plasma membrane (PM) of the germination site and to the apical PM of growing pollen tubes. We demonstrated that the PM redistribution of BDR8 and BDR9 during pollen germination relies on ROPs but not vice versa. Furthermore, enhanced expression of BDR8 partially restored germination of rop1 pollen but had no effects on that of the quadruple rop pollen, supporting their genetic epistasis. Results presented here demonstrate an ROP signaling route essential for pollen germination, which supports evolutionarily conserved roles of Rho GTPases in polarity establishment.

Preparation and identification of isoquinoline alkaloids with ATP citrate lyase inhibitory activity from Dactylicapnos scandens.

Three new isoquinoline alkaloids including a morphine derivative (1), two aporphine alkaloids (2-3), together with five known alkaloids (4-8) were obtained from the extract of Dactylicapnos scandens (D.Don) Hutch. (D. scandens). Their structures and absolute configurations were elucidated by extensive spectroscopic data analysis including HRESIMS, NMR and electronic circular dichroism (ECD) and ECD calculation. Compounds 1-8 were evaluated for ATP Citrate Lyase (ACLY) inhibitory activity through an enzymatic assay. Among them, 2 and 3 showed the high ACLY inhibitory activity with an IC50 value of 10.48 ± 1.59 and 10.89 ± 4.89 µM.

Humulus lupulus L. extract and its active constituent xanthohumol attenuate oxidative stress and nerve injury induced by iron overload via activating AKT/GSK3ß and Nrf2/NQO1 pathways.

Hops, the dried female clusters from Humulus lupulus L., have traditionally been used as folk medicines for treating insomnia, neuralgia, and menopausal disorders. However, its pharmacological action on iron overload induced nerve damage has not been investigated. This study aims to evaluate the protective effects of hops extract (HLE) and its active constituent xanthohumol (XAN) on nerve injury induced by iron overload in vivo and in vitro, and to explore its underlying mechanism. The results showed that HLE and XAN significantly improved the memory impairment of iron overload mice, mainly manifested as shortened latency time, increased crossing platform times and spontaneous alternation ratio, and increased the expression of related proteins. Additionally, HLE and XAN significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and remarkably decreased malondialdehyde (MDA) level in hippocampus. Also, HLE and XAN apparently reduced reactive oxygen species (ROS) content of PC12 cells induced by iron dextran (ID), and improved the oxidative stress level. Moreover, HLE and XAN significantly upregulated the expression of nuclear factor E2-related factor (Nrf2), NAD(P)H quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), SOD, phosphorylated AKT (p-AKT), and phosphorylated GSK3ß (p-GSK3ß) both in hippocampus and PC12 cells. These findings demonstrated the protective effect of HLE and XAN against iron-induced memory impairment, which is attributed to its antioxidant profile by activation of AKT/GSK3ß and Nrf2/NQO1 pathways. Also, it was suggested that hops could be a potential candidate for iron overload-related neurological diseases treatment.

Impact of environmental factors on the ammonia-oxidizing and denitrifying microbial community and functional genes along soil profiles from different ecologically degraded areas in the Siding mine.

Ammonia oxidizers (ammonia-oxidizing bacteria (AOB amoA) and ammonia-oxidizing archaea (AOA amoA)) and denitrifiers (encoded by nirS, nirK and nosZ) in the soil nitrogen cycle exist in a variety of natural ecosystems. However, little is known about the contribution of these five N-related functional genes to nitrification and denitrification in the soil profile in severely ecologically degraded areas. Therefore, in the present study, the abundance, diversity and community composition of AOA, AOB, nirS, nirK and nosZ were investigated in the soil profiles of different ecologically degraded areas in the Siding mine. The results indicated that, at the phylum level, the dominant archaea were Crenarchaeota and Thaumarchaeota and the dominant bacteria were Proteobacteria. Heavy metal contents had a great impact on AOA amoA, nirS and nirK gene abundances. AOA amoA contributed more during the ammonia oxidation process and was better adapted for survival in heavy metal-contaminated environments. In addition to heavy metals, the soil organic matter (SOM) content and C/N ratio had strong effects on the AOA and AOB community diversity and structure. In addition, variations in the net ammonification and nitrification rates were proportional to AOA amoA abundance along the soil profile. The soil C/N ratio, soil available phosphorus content and soil moisture influenced the denitrification process. Both soil available phosphorus and moisture were more strongly related to nosZ than to nirS and nirK. In addition, nosZ presented a higher correlation with the nosZ/(nirS + nirK) ratio. Moreover, nosZ/(nirS + nirK) was the key functional gene group that drove the major processes for NH4+-N and NO3--N transformation. This study demonstrated the role and importance of soil property impacts on N-related microbes in the soil profile and provided a better understanding of the role and importance of N-related functional genes and their contribution to soil nitrification and denitrification processes in highly degraded areas in the Siding mine.

Artemisinin suppressed tumour growth and induced vascular normalisation in oral squamous cell carcinoma via inhibition of macrophage migration inhibitory factor.

BACKGROUND: Tumour vascular normalisation therapy advocates a balance between pro-angiogenic factors and anti-angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported. METHODS: Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK-8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF. RESULTS: Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL-8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL-8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART-treated cells. CONCLUSION: Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway.

Hypoxia promotes the expression of Von Willebrand factor in breast cancer cells by up-regulating the transcription factor YY1 and down-regulating the hsa-miR-424.

Von Willebrand factor (VWF), a large glycoprotein with hemostatic properties, is mainly synthesized by megakaryocytes and endothelial cells (ECs). In recent years, studies have found that tumor cells also can produce VWF de novo. Tumor growth is usually accompanied by hypoxic environment, and whether hypoxia will influence von Willebrand factor production in tumor cells is still unknown. In this research, we demonstrated that hypoxia could induce the production of VWF in breast cancer cells (MCF-7 and MDA-MB-231 cell lines), and promoted cell migration as well as angiogenesis. Notably, VWF is a key factor for hypoxia to promote breast cancer cell migration and angiogenesis, and knocking down VWF can attenuate the effects of hypoxia. Further study was conducted on the molecular mechanism to clarify why hypoxia can promote VWF synthesis in breast cancer cells. We found that Yin-Yang 1 (YY1, a transcription factor) had a binding site to the promoter region of VWF, and acted as a transcriptional activator of VWF. Meanwhile, hsa-miR-424 inhibited VWF production by associating with the 3'-UTR of VWF mRNA. Here, we proved that hypoxia up-regulated the transcription factor YY1 and down-regulated hsa-miR-424 to increase the expression level of VWF. Additionally, knockdown of transcription factor YY1 and transfection of hsa-miR-424 mimics had a synergistic effect in reducing hypoxia-induced VWF production of breast cancer cells, cell migration and angiogenesis in vitro.

A Mixed Methods Investigation of the Prevalence and Influencing Factors of Compassion Fatigue among Midwives in Different Areas of China.

Objective: Exploring the influencing factors of compassion fatigue among midwives to prevent compassion fatigue from occurring and improve their mental health. Methods: A method integrating the quantitative research method and qualitative research method is used. For the quantitative research, a cross-sectional study was carried out. State-run hospitals from three economic areas in China were selected as investigation scope from June 2018 to May 2021. A total of 515 midwives were chosen randomly from three economic areas. SPSS 22.0 was used for data cleaning and statistical description and analysis. The influencing factors of compassion fatigue among midwives were analyzed by fitting these two-level logistic models. For qualitative research, purposive sampling and maximum variation strategy were used to select midwives with mild or above compassion fatigue in the questionnaire survey. Field study and interviews were used to collect data. Results: The results in the quantitative research showed that 515 valid questionnaires were received with 82.14% of midwives whose compassion fatigue were moderate or above. Multilevel statistical model analysis demonstrated that hospital level, children situation, area, working atmosphere, experiences of traumatic delivery, sleep quality, and social support level had impacts on the degree of midwives' compassion fatigue (p < 0.05). The result in the qualitative research showed that 34 midwives were interviewed, and 7 topic ideas were refined. Conclusion: Overall, the incidence of compassion fatigue among midwives is high. Risk factors influencing the degree of midwives' compassion fatigue include lower social support, disharmonious working atmosphere, toddler situation, huge workload, experiences of traumatic delivery, and poor quality of sleep.

[Bibliometric analysis on key elements of clinical application of acupoint catgut embedding therapy in recent ten years].

OBJECTIVE: To analyze the characteristics of acupoint catgut embedding methods, tools, catgut types, and the treatment cycles in the clinical research in recent ten years both at home and abroad, so as to summarize its regularities and to provide technical references for further studies. METHODS: Articles about clinical researches on catgut embedding therapy published in recent ten years (from January 1, 2010 to December 31,2020) were retrieved from the databases of CNKI, Wanfang, VIP, and PubMed by using key words of "acupoint embedding" "acupoint catgut embedding" and "catgut implantation at acupoint". According to the inclusion and exclusion criteria, a new database was established for analyzing the data mentioned above. RESULTS: 1) A total of 1 196 articles were collected, including 15 English articles and 1 181 Chinese articles, presenting a fluctuating increasing trend in recent ten years. 2) The commonly used acupoint embedding methods included disposable catgut embedment needle method (399 times, 38.89%) and disposable syringe needle catgut embedding method (347 times, 33.82%), for which two or multiple methods were mentioned in the same one article. 3) The most frequently used top two tools for catgut embedding were the dispo-sable catgut embedment needle (463 times, 43.03%) and disposable syringe needle (406 times,37.73%), with a significant increase in the application of disposable syringe needle. The most commonly used size of tools included No. 7 (283 times, 39.86%), No. 9 (196 times, 27.61%) and No. 8 (109 times, 15.35%). 4) The most frequently implanted surgical suture was still the common catgut (671 times, 58.15%) despite of a reduction in clinical application year by year, and the types of the implanted suture materials were gradually enriched since 2018, such as the absorbable surgical suture, polyethylprolactide(PGLA), collagen protein thread, polydioxanone(PPDO), etc. The commonly used implanted catgut size was 3-0 (227 times, 30.15%), 2-0 (176 times, 23.37%), 4-0 (131 times, 17.40%), 0 (103 times, 13.68%), with the commonly used catgut length being 1 cm (332 times, 35.55%), 1.5 cm (103 times, 11.03%), 1-2 cm (92 times, 9.85%) and 2 cm (92 times, 9.85%). 5) The intervals of the catgut implantation were 7 days (313 times, 28.95%), 14 days (262 times, 24.24%), 10 days (174 times, 16.10%), and 15 days (162 times, 14.99%). CONCLUSION: In recent ten years, clinical research on acupoint catgut embedding is growing rapidly, and the embedding methods, tools, implanted sutures, and embedding intervals are various, which may provide certain technical references for the future researches and suggest an urgent need of formulation of the standardized and unified standards in this field.

Rapid Limit Test of Seven Pesticide Residues in Tea Based on the Combination of TLC and Raman Imaging Microscopy.

Numerous studies have shown that pesticide residues in tea exceeding the maximum residue limits (MRL) can cause harmful effects on the human body. There are many limitations in the existing analytical methods for pesticide residues in tea, so new analytical methods need to be developed. We developed a limit test method that combines thin-layer chromatography with Raman imaging microscopy (TLC-RIM). Seven residual pesticide components in tea (Avermectin, Methomyl, Carbendazim, Imidacloprid, Chlorothalonil, Azoxystrobin, and Acetamiprid) could be preliminarily separated by TLC and then irradiated by a 532 nm laser. Raman spectra of seven pesticides obtained by Raman imaging microscopy could be used to test whether the pesticide residues in tea exceed the MRL. The limits of detection of the seven pesticides were 0.04, 0.10, 0.24, 0.20, 0.12, 0.12, and 1.0 mg/mL, respectively. The simulated positive test showed that the matrix in tea did not interfere with the test of the seven pesticides. When the pesticides were tested within 8 h, the RSD of the peak heights of the seven pesticides were 1.2%~9.6%; the test results of three batches of tea showed that the imidacloprid in one batch of tea exceeded its MRL, and the results were consistent with that by UPLC-MS/MS. The TLC-RIM is fast, sensitive, stable, specific, and reliable.