Grain industrial agglomeration and grain green total factor productivity in China: A dynamic spatial durbin econometric analysis.

Appropriate industrial agglomeration has several benefits, including reducing environmental pollution, promoting innovation and enhancing grain green total factor productivity (GTFP). It is an effective strategy for promoting high-quality and sustainable development in the grain industry. In this study, the slacks-based measure of the global Malmquist-Luenberger (SBM-GML) model is used to estimate China's grain GTFP using the panel data of 31 provinces from 2001 to 2020. Furthermore, a dynamic spatial econometric model is employed to empirically investigate the impact of grain industry agglomeration on grain GTFP and its regional heterogeneity. The results show that GTFP exhibits a fluctuating growth tendency, with advancements in green technology serving as the primary engine of that expansion. (2) The deepening of grain industrial agglomeration has a long-term promoting effect on the grain GTFP of local and neighbouring areas, with the long-term effect being more significant than the short-term effect, as revealed by the dynamic spatial Durbin model. (3) According to the heterogeneity analysis, industrial agglomeration's impact on grain GTFP is most noticeable in the production and sales balance. Therefore, encouraging regional cooperation and communication while raising the grain industrial agglomeration standard is crucial. The degree of regional economic growth, the state of the agricultural infrastructure and the conditions of the natural resources should all be considered by policymakers when developing distinct and focused policy assistance for each region.

Comparative analysis of the vaginal bacteriome and virome in healthy women living in high-altitude and sea-level areas.

The vaginal microbiota plays an important role in the health of the female reproductive tract and is closely associated with various pregnancy outcomes and sexually transmitted diseases. Plenty of internal and external factors have strong influence on the changes in a woman's vaginal microbiome. However, the effect of a high-altitude on female vaginal microbiota has not been described. In this study, we characterized the vaginal bacteriome and virome of 13 and 34 healthy women living in high-altitude and sea-level areas, using whole-metagenome shotgun sequencing of their vaginal mucus samples. The results revealed that the vaginal bacteriomes of high-altitude individuals are featured by a significant increase of species diversity, depletion of Lactobacillus crispatus, and more abundant of some anaerobic bacteria, such as Chlamydia trachomatis, Mageeibacillus indolicus, Dialister micraerophilus, and Sneathia amnii). In addition, the vagina samples of sea-level subjects harbor more Lactobacillus strains, whereas the anaerobic bacteroidetes strains mostly appeared in high-altitude subjects. Identified and assembled 191 virus operational taxonomic units (vOTUs), there were significant differences in the abundance of 107 vOTUs between the two groups. Together, the results of this study raised the understanding of bacteriome and virome in the vagina of women at different elevations, and demonstrated that the vaginal microbiome is related to the high-altitude geographic adaptation.

Rationality of the ethanol precipitation process in modern preparation production of Zishui-Qinggan decoction evaluated by integrating UPLC-QTOF-MS/MS-based chemical profiling/serum pharmacochemistry and network pharmacology.

INTRODUCTION: Zishui-Qinggan decoction (ZQD) is a classical traditional Chinese medicine formula (TCMF) for alleviating menopausal symptoms (MPS) induced by endocrine therapy in breast cancer patients. In the production of TCMF modern preparations, ethanol precipitation (EP) is a commonly but not fully verified refining process. OBJECTIVES: Chemical profiling/serum pharmacochemistry and network pharmacology approaches were integrated for exploring the rationality of the EP process in the production of ZQD modern preparations. MATERIAL AND METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was applied to identify the chemical profiles and absorbed components of ZQD. Network pharmacology was used to identify targets and pathways related to MPS-relieving efficacy. RESULTS: The chemicals of ZQDs without/with EP process (referred to as ZQD-W and ZQD-W-P, respectively) were qualitatively similar with 89 and 87 components identified, respectively, but their relative contents were different; 51 components were detectable in the serum of rats orally administered with ZQD-W, whereas only 19 were detected in that administered with ZQD-W-P. Key targets, such as AKT1, and pathways, such as the PI3K-Akt signalling pathway, affected by ZQD-W and ZQD-W-P were similar, while the neuroactive ligand-receptor interaction pathway among others and the MAPK signalling pathway among others were specific pathways affected by ZQD-W and ZQD-W-P, respectively. The specifically absorbed components of ZQD-W could combine its specific key targets. CONCLUSION: The EP process quantitatively altered the chemical profiles of ZQD, subsequently affected the absorbed components of ZQD, and then affected the key targets and pathways of ZQD for relieving MPS. The EP process might result in variation of the MPS-relieving efficacy of ZQD, which deserves further in vivo verification.

Quality evaluation of Pterocephali Herba through simultaneously quantifying 18 bioactive components by UPLC-TQ-MS/MS analysis.

Pterocephali Herba (PH), the dried whole plant of Pterocephalus hookeri, is a Tibetan medicine commonly used to treat rheumatoid arthritis (RA). Iridoids, triterpenoids, flavonoids and phenylpropanoids are the major groups of bioactive constituents from PH. However, only ursolic acid and oleanolic acid, two unspecific triterpenoid components, are used as markers for the quality control of PH in Chinese Pharmacopoeia. Herein, an UPLC-TQ-MS/MS integrating SIR and MRM mode method for simultaneously quantifying 18 components, i.e., 9 iridoids, 3 triterpenoids, 3 phenylpropanoids, 2 flavonoids and quinic acid, in PH was developed and validated, and was used to evaluate 10 batches of PH samples from different origins. Hierarchical cluster analysis (HCA) was used to show the clustering of PH samples, while spearman correlation analysis was adopted to evaluate the correlation between ursolic acid/oleanolic acid and other quantified components. It was found that the established method was sensitive, precise, and accurate enough for the simultaneous quantification of 18 analytes in PH samples. Significant differences were found among the contents of 18 components in PH samples, no apparent clustering of the quality of PH samples was found to be related to its origins, and the contents of ursolic acid/oleanolic acid were only significantly correlated to the content of sylvestroside I, dipsanoside B, dipsanoside A in PH. Our results suggested that the newly established multi-components quantitative method is an improved approach for quality evaluation of PH samples. Furthermore, the holistic quality was inconsistent among PH samples, and ursolic acid/oleanolic acid alone could not indicate the holistic quality variation trend of PH.

Modulation of Xiongdanjiuxin pills on the gut-liver axis in high-fat diet rats.

AIM: Xiongdanjiuxin pill (XP) is a traditional Chinese medicine formula for the prevention and treatment of hyperlipidemia (HLP) and related complications. In this study, the gut-liver axis was used as the breakthrough point to analyze the therapeutic effect and potential mechanism of XP on HLP model rats and related complications. MAIN METHODS: We used high-fat diet (HFD) to establish the HLP model of rats and treated them with XP. The 16S rRNA sequencing method was used to explore the effect of XP on the gut microbiota of HFD rats, and the effects of XP on ileum pathology, intestinal barrier and circulatory inflammation in HFD rats were also investigated. We further explored the molecular mechanism of XP treating liver inflammation in rats with HFD by regulating toll-like receptor 4 (TLR4) signaling. KEY FINDINGS: We found that XP could regulate the imbalance of gut microbiota in HFD rats, and up-regulate the expression of tight junction protein in intestinal epithelium of HFD rats, thereby improving the intestinal barrier damage and intestinal inflammatory response. In addition, XP could significantly reduce the levels of inflammatory cytokines in HFD rats, and inhibit TLR4 signaling pathway, thereby reducing liver inflammation in HFD rats. SIGNIFICANCE: XP can effectively improve the imbalance of gut-liver axis in hyperlipidemic rats and alleviate the inflammatory damage of liver. Its mechanism may be related to regulating the disorder of gut microbiota and inhibiting TLR4 signal pathway, so as to achieve the therapeutic effect on hyperlipidemic fatty liver in rats.

Pd-Catalyzed Multicomponent Cross-Coupling of Allyl Esters with Alkyl Bromides and Potassium Metabisulfite: Access to Allylic Sulfones.

A Pd-catalyzed multicomponent cross-coupling of allyl esters with alkyl bromides to synthesize allylic sulfones by using K2S2O5 as a connector is first reported. The reaction displays a broad range of substrate generality along with excellent functional group compatibility and produces the products with high regioselectivity (only E). Furthermore, the biologically active molecules with a late-stage modification, including aspirin, menthol, borneol, and estrone, are also highly compatible with the multicomponent cross-coupling reaction. Mechanistic studies indicate that the process of SO2 insertion into the C-Pd bond was involved in this transformation.

UPLC-QTOF-MS/MS assisted UPLC-TQ-MS/MS strategy to comparatively investigate the rat pharmacokinetics of N-acetyldopamine oligomers derived from Cicadae Periostracum.

Cicadae Periostracum (CP), the slough molted from the nymph of Cryptotympana pustulata, is a widely used medicinal material in traditional Chinese medicine (TCM). N-acetyldopamine oligomers (NAOs), the homologues of acetyldopamine, including N-acetyldopamine dimers/trimers/tetramers/pentamers (NADs/NATrs/NATes/NAPs), side-chain isomer of dimers/trimers (SCIDs/SCITrs), are major bioactive ingredients of CP. However, owing to commercially unavailable reference substances of all NAOs, simultaneous quantification of these NAOs in biological samples is difficult, and thus their pharmacokinetics are still unknown. In this study, a comprehensive strategy for simultaneous quantification/semi-quantification of NAOs in plasma with single N-acetyldopamine dimer A (NAD-A) as reference substance was established and comparatively investigated their pharmacokinetics after oral administration of pure NAD-A and two types of CP extracts, i.e., post-molting-washed slough (CP-WAT) and pre-molting-washed slough (CP-WBT). A UPLC-QTOF-MS/MS assisted UPLC-TQ-MS/MS strategy was developed to quantify NAOs in rat plasma. NAOs in CP extract were qualitatively characterized by UPLC-QTOF-MS/MS, then the quasi-molecular ions and characteristic fragment ions of the identified NAOs by UPLC-QTOF-MS/MS were transferred to UPLC-TQ-MS/MS as parent-daughter ion pairs for MRM mode quantification of the NAOs, and the method was validated with single NAD-A for quantifying NAD-A and semi-quantifying other NAOs in plasma. The established method was applied to compare the pharmacokinetics of NAOs after oral administration of NAD-A and the extracts of CP-WBT/CP-WAT respectively. Six quasi-molecular ions and characteristic fragment ion m/z 192.1 were characterized by UPLC-QTOF-MS/MS and transferred to be the parent-daughter ion pairs for UPLC-TQ-MS/MS analysis of six kinds of NAOs. For the pharmacokinetics, NAD-A showed double peaks absorption character when administered with single compound, but with higher relative bioavailability when administered with CP extracts with the similar dosage. Compared with CP-WAT, NAOs in CP-WBT reached the maximum plasma concentration in much shorter time.

Term breech presentation vaginal births in Tibet: A retrospective analysis of 451 cases.

Background: In high altitude areas, like Tibet, most fetuses in breech presentation at term are delivered vaginally owing to a variety of reasons, but this has not been published. Objective: This study aimed to provide references and evidence for the delivery of breach presentation term fetuses in high altitude areas, through comparing and analyzing the data of full-term singleton fetuses with breech or cephalic presentation in Naqu People's Hospital, Tibet. Study design: We retrospectively analyzed the clinical data of 451 breech presentation fetuses mentioned above over a period of 5 years (2016-2020). A total of 526 cephalic presentation fetuses' data within 3 months (1 June to 1 September 2020) of the same period were collected too. Statistics were compared and assembled on fetal mortality, Apgar scores, and severe neonatal complications for both planned cesarean section (CS) and vaginal delivery. In addition, we also analyzed the types of breech presentation, the second stage of labor, and damage to the maternal perineum during vaginal delivery. Results: Among the 451 cases of breech presentation fetuses, 22 cases (4.9%) elected for CS and 429 cases (95.1%) elected for vaginal delivery. Of the women who chose vaginal trial labor, 17 cases underwent emergency CSs. The perinatal and neonatal mortality rate was 4.2% in the planned vaginal delivery group and the incidence of severe neonatal complications was 11.7% in the transvaginal group, no deaths were detected in the CS group. Among the 526 cephalic control groups with planned vaginal delivery, the perinatal and neonatal mortality was 1.5% (p = 0.012), and the incidence of severe neonatal complications was 1.9%. Among vaginal breech deliveries, most of them were complete breech presentation (61.17%). Among the 364 cases, the proportion of intact perinea was 45.1%, and first degree lacerations accounted for 40.7%. Conclusion: In the Tibetan Plateau region, vaginal delivery was less safe than cephalic presentation fetuses for full-term breech presentation fetuses delivered in the lithotomy position. However, if dystocia or fetal distress can be identified in time and then encouraged to convert to cesarean, its safety will be greatly improved.

Assessment of iris volume in glaucoma patients with type 2 diabetes mellitus by AS-OCT.

AIM: To examine the change of iris volume measured by CASIA2 anterior segment optical coherence tomography (AS-OCT) in glaucoma patients with or without type 2 diabetes mellitus (T2DM) and explore if there is a correlation between hemoglobin A1c (HbA1c) level and iris volume. METHODS: In a cross-sectional study, 72 patients (115 eyes) were divided into two groups: primary open angle glaucoma (POAG) group (55 eyes) and primary angle-closure glaucoma (PACG) group (60 eyes). Patients in each group were separately classified into patients with or without T2DM. Iris volume and glycosylated HbA1c level were measured and analyzed. RESULTS: In the PACG group, diabetic patients' iris volume was significantly lower than those of non-diabetics (P=0.02), and there was a significant correlation between iris volume and HbA1c level in the PACG group (r=-0.26, P=0.04). However, diabetic POAG patients' iris volume was noticeably higher than those of non-diabetics (P=0.01), and there was a significant correlation between HbA1c level and iris volume (r=0.32, P=0.02). CONCLUSION: Diabetes mellitus impact iris volume size, as seen by increased iris volume in the POAG group and decreased iris volume in the PACG group. In addition, iris volume is significantly correlated with HbA1c level in glaucoma patients. These findings imply that T2DM may compromise iris ultrastructure in glaucoma patients.

Efficacy and safety of HAIC alone vs. HAIC combined with lenvatinib for treatment of advanced hepatocellular carcinoma.

To investigate efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib (HAIC-Len) and HAIC alone for the treatment of advanced hepatocellular carcinoma (Ad-HCC). Totally 349 patients with Ad-HCC participated in the research from February 2018 to October 2020. On the basis of propensity score matching (PSM), 132 and 110 cases were assigned to the HAIC group and the HAIC-Len group, respectively, with a ratio of 1:1. Progression-free survival (PFS), overall survival (OS), and complications were compared between two groups. The Kaplan-Meier method and log-rank test were utilized to estimate cumulative OS and PFS. Additionally, uni- and multi-variate Cox regression models were employed to identify significant independent factors. The median follow-up period in this study was set to be 20.8 months. Following PSM, the one-, two- and three-year cumulative OS rates in the HAIC-Len and HAIC groups were 63.6%, 12.1%, and 3.0%, and 47.2%, 11.8%, and 2.7%, respectively, with a significant difference (P < 0.001). The first-three-year cumulative incidence rates PFS in the HAIC-Len and the HAIC groups were 15.2%, 1.5%, and ND, and 11.8%, 4.5%, and 3.6%, respectively, with no significant difference detected (P = 0.092). BMI (HR 0.709. 95% CI 0.549, 0.915. P = 0.008) and AST (HR 1.005. 95% CI 1.003, 1.007. P < 0.001) represented independent prognostic factors for OS. Additionally, the two groups exhibited no significant difference in the incidence rates of adverse events. HAIC-Len significantly improved survival outcomes of patients with Ad-HCC and demonstrated acceptable toxicity compared to HAIC alone.

Comparing steamed and wine-stewed Rehmanniae Radix in terms of Yin-nourishing effects via metabolomics and microbiome analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmanniae Radix Praeparata (RRP), the processed root of Rehmannia glutinosa, has been widely used to treat Yin deficiency syndrome in traditional Chinese medicine. RRP is available in two forms: processed by steaming with water (SRR) or processed by stewing with yellow rice wine (WRR). Previous work has documented chemical differences in the secondary metabolomes and glycomes of SRR and WRR. AIM OF THE STUDY: This study aimed to compare SRR and WRR in terms of Yin-nourishing effects via metabolomics and microbiome analysis. MATERIALS AND METHODS: ICR mice were orally administered with thyroxine for 14 d to induce Yin deficiency. Changes in biochemical indices and histopathology were detected. Serum metabolomics analysis and microbial 16S rRNA sequencing were performed to compare the therapeutic effects and mechanisms between SRR and WRR in treating thyroxine-induced Yin deficiency. RESULTS: Both SRR and WRR decreased serum T3, T4 and MDA levels, and increased SOD activity. SRR more effectively decreased serum Cr, and ameliorated kidney injury, while WRR showed better regulation on ratio of cAMP/cGMP and serum TSH, and relieved thyroid injury. Both SRR and WRR regulated tyrosine, glycerophospholipid, and linoleic acid metabolism and the citric acid cycle. Additionally, SRR regulated fatty acid metabolism, while WRR influenced alanine, aspartate and glutamate metabolism, and bile acid biosynthesis. SRR significantly enriched the genera Staphylococcus and Bifidobacterium in the gut microbiome, while WRR significantly enriched the genera Akkermansia, Bacteroides and Parabacteroides, and decreased the abundance of Lactobacillus. CONCLUSIONS: SRR displayed better protective effects on kidney, while WRR showed stronger effects on thyroid in thyroxine-induced Yin deficient mice. These differences might be due to different regulating effects of SRR and WRR on the metabolome and gut microbiota.