Berberine and magnolol exert cooperative effects on ulcerative colitis in mice by self-assembling into carrier-free nanostructures.

The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals.

Whether unplanned excision on synovial sarcoma will influence the prognosis? An retrospective analysis of prognostic factors in 54 synovial sarcoma cases at a single center.

OBJECTIVE: In this study, we examined the reason and prognosis of unplanned excision on synovial sarcoma. METHODS: We retrospectively analyzed 54 patients diagnosed with synovial sarcoma between March 2013 and February 2021, including 26 cases of unplanned excision surgery. Patients were divided into two groups based on whether they underwent unplanned excision. Then, factors such as gender, age, tumor size, tumor location, American Joint Committee on Cancer (AJCC) staging, unplanned excision, time of onset, duration of disease, radiotherapy, chemotherapy, amputation, local recurrence factors, and death were statistically evaluated. RESULTS: The results of a multivariate analysis revealed that the AJCC staging is an independent factor for patient prognosis. When patients were divided into two groups, those who had undergone unplanned excision and those who had not, statistical analysis revealed that there was no difference of survival between two groups, but tumor size and AJCC staging had statistical difference. To further explore the influences of unplanned excision, we performed propensity score analysis with 1:1 matching using the nearest neighbor matching method to balance the covariates between the two groups. There was no difference of survival between two groups after propensity score matching. CONCLUSION: Unplanned excision is commonly performed in synovial sarcoma and do not impact the prognosis after extensive resection.

Comparison of exsanguination and hemostasis devices for Limb surgery: a multicenter randomized controlled study.

BACKGROUND: Excessive intraoperative bleeding remains a challenge in limb surgeries. The exsanguination tourniquet ring has emerged as a potential solution for effective exsanguination and hemostasis. This study aims to evaluate its efficacy and safety compared to the conventional exsanguination and hemostasis approach (pneumatic tourniquet combined with Esmarch bandage). METHODS: This randomized controlled trial evaluates the exsanguination tourniquet ring's effectiveness and safety versus the conventional approach in 220 participants undergoing various limb surgeries. Allocation included experimental and control groups, assesses through efficacy (including intraoperative and total blood loss, hemoglobin levels, and exsanguination and hemostasis effectiveness) and safety (adverse event occurrence) indicators. RESULTS: The experimental group (n = 110) utilizes the exsanguination tourniquet ring, while the control group (n = 110) employs the conventional approach. As for intraoperative blood loss, the experimental group is non-inferior to the control group (p-value < 0.001). While no significant difference is found in total blood loss (for the full analysis set, p-value = 0.442; for the per protocol set, p-value = 0.976) and differences in postoperative and preoperative hemoglobin levels (for the full analysis set, p-value = 0.502; for the per protocol set, p-value = 0.928). Regarding exsanguination and hemostasis effectiveness, the full analysis set reveals significantly superior ratings in the experimental group compared to the control group (p-value = 0.002 < 0.05), while the per protocol set analysis indicates no significant difference between the groups (p-value = 0.504). As for safety indicators, adverse events related to the device are minimal in two groups, with only one severe event unrelated to the device. CONCLUSIONS: The exsanguination tourniquet ring is an effective and safe device for intraoperative blood loss control in various limb surgeries. TRIAL REGISTRATION: Comparison of Exsanguination and Hemostasis Devices for Limb Surgery A Prospective Multicenter Randomized Controlled Study, ChiCTR2300077998, 11/27/2023.

Chemical-Assisted CO2 Water-Alternating-Gas Injection for Enhanced Sweep Efficiency in CO2-EOR.

CO2-enhanced oil recovery (CO2-EOR) is a crucial method for CO2 utilization and sequestration, representing an important zero-carbon or even negative-carbon emission reduction technology. However, the low viscosity of CO2 and reservoir heterogeneity often result in early gas breakthrough, significantly reducing CO2 utilization and sequestration efficiency. A water-alternating-gas (WAG) injection is a technique for mitigating gas breakthrough and viscous fingering in CO2-EOR. However, it encounters challenges related to insufficient mobility control in highly heterogeneous and fractured reservoirs, resulting in gas channeling and low sweep efficiency. Despite the extensive application and research of a WAG injection in oil and gas reservoirs, the most recent comprehensive review dates back to 2018, which focuses on the mechanisms of EOR using conventional WAG. Herein, we give an updated and comprehensive review to incorporate the latest advancements in CO2-WAG flooding techniques for enhanced sweep efficiency, which includes the theory, applications, fluid displacement mechanisms, and control strategies of a CO2-WAG injection. It addresses common challenges, operational issues, and remedial measures in WAG projects by covering studies from experiments, simulations, and pore-scale modeling. This review aims to provide guidance and serve as a reference for the application and research advancement of CO2-EOR techniques in heterogeneous and fractured reservoirs.

A Heterogeneous Viscosity Flow Model for Liquid Transport through Nanopores Considering Pore Size and Wettability.

The confinement effect in micro- and nanopores gives rise to distinct flow characteristics in fluids. Clarifying the fluid migration pattern in confined space is crucial for understanding and explaining the abnormal flow phenomena in unconventional reservoirs. In this study, flow characteristics of water and oil in alumina nanochannels were investigated with diameters ranging from 21 nm to 120 nm, and a heterogeneous viscosity flow model considering boundary fluid was proposed. Compared with the prediction of the HP equation, both types of fluids exhibit significant flow suppression in nanochannels. As the channel size decreases, the deviation degree increases. The fluid viscosity of the boundary region displays an upward trend as the channel size decreases and the influence of the interaction between the liquid and solid walls intensifies. The thickness of the boundary region gradually decreases with increasing pressure and eventually reaches a stable value, which is primarily determined by the strength of the interaction between the liquid and solid surfaces. Both the pore size and wettability are essential factors that affect the fluid flow. When the space scale is extremely small, the impact of wettability becomes more pronounced. Finally, the application of the heterogeneous flow model for permeability evaluation has yielded favorable fitting results. The model is of great significance for studying the fluid flow behavior in unconventional reservoirs.

Quantitative Characterization of Adhesion Work on Shale Surfaces and Discussion on the Influence of Roughness Based on Atomic Force Microscopy (AFM).

Adhesion is an intrinsic property of rocks and liquids. Investigating the factors contributing to its formation and the mechanisms governing its action is crucial for elucidating the adhesion work between solids and liquids. The adhesion work, serving as a parameter that characterizes the energy changes during the solid-liquid contact process, is a vital tool for probing this phenomenon. However, conventional measurements of the adhesion work are significantly influenced by surface roughness and fail to differentiate local variations in the adhesion performance. This limitation obscures our understanding of the primary adsorption sites and mechanisms between solids and liquids, posing significant challenges to the study of rock surface properties. In this study, in conjunction with scanning electron microscopy and contact angle analyses, we elucidated for the first time the locations where voids form during the solid-liquid contact process, the lithological composition of rough areas, and their impact on the adhesion work between water/oil and the surfaces. Additionally, employing atomic force microscopy (AFM), we examined the variations in water/oil-solid adhesion work across different characteristic regions, thereby characterizing the overall hydrophilic/hydrophobic properties of the rock core. Specific conclusions are as follows: (1) A negative correlation exists between roughness and the contact angle adhesion work, with heterogeneity impeding liquid-rock contact; (2) By comparing the strength of water-solid/oil-solid adhesion work within localized areas, we delineated the adhesion work characteristics of samples and their primary generation sites, with oil-solid adhesion work in target blocks predominantly originating from quartz, clay minerals, and organic matter; (3) The influence of pore throat development on the overall adhesion work of samples was clarified, demonstrating that an increase in the proportion of internal rock pores enhances the surface oil-solid adhesion work; (4) A dimensionless wetting index I was established to mitigate the impact of roughness on the expression of adhesion work, exhibiting a strong correlation with traditional evaluation methods.

mTORC1 accelerates osteosarcoma progression via m6A-dependent stabilization of USP7 mRNA.

Osteosarcoma (OS) is considered a sex steroid hormone-dependent bone tumor. The development and progression of OS are regulated by 17ß-estradiol (E2). However, the detailed mechanisms of E2-modulated OS progression remained to be elucidated. Here, we found that E2-activated mammalian target of rapamycin (mTOR) signaling promoted N6-methyladenosine (m6A) modification through regulating WTAP. Inhibition of mTOR complex 1 (mTORC1) reversed E2-activated WTAP expression. Meanwhile, inhibition of mTORC1 suppressed OS cell proliferation and migration. Deficiency of TSC2 activated mTORC1 signaling and enhanced OS cell proliferation and migration, while abrogated by Rapamycin. Interestingly, mTOMC1 promoted mRNA stability of ubiquitin-specific protease 7 (USP7) through m6A modification. Loss of USP7 suppressed the proliferation, migration, and ASC specks, while promoted apoptosis of OS cells. USP7 interacted with NLRP3 and deubiquitinated NLRP3 through K48-ubiquitination. USP7 was upregulated and positive correlation with NLRP3 in OS patients with high level of E2. Loss of USP7 suppressed the progression of OS via inhibiting NLRP3 inflammasome signaling pathway. Our results demonstrated that E2-activtated mTORC1 promoted USP7 stability, which promoted OS cell proliferation and migration via upregulating NLRP3 expression and enhancing NLRP3 inflammasome signaling pathway. These results discover a novel mechanism of E2 regulating OS progression and provide a promising therapeutic target for OS progression.

Analogy of silicon and boron in plant nutrition.

Silicon (Si) and boron (B) are a class of elements called metalloids, which have properties like metals and non-metals. Si is classified as a quasi-essential element, while B is a micronutrient element for plants. Nowadays, numerous discoveries have shown the analogy of silicon and boron in plant nutrition. In this minireview, the molecular mechanisms for the transport of these two metalloids are compared. We also discussed the chemical forms of Si and B and their functional similarity in response to environmental stresses in plants. In conclusion, it can be proposed that cell wall-bound silicon rather than silica might partially replace boron for plant growth, development, and stress responses, and the underlying mechanism is the Si contribution to B in its structural function.

Genome Mining of Cinnamoyl-Containing Nonribosomal Peptide Gene Clusters Directs the Production of Malacinnamycin.

Cinnamoyl-containing nonribosomal peptides (CCNPs) constitute a unique family of actinobacterial secondary metabolites that display a broad spectrum of biological activities. Here, we present a genome mining approach targeting cyclase and is isomerase to discover new CCNPs, which led to the identification of 207 putative CCNP gene clusters from public bacterial genome databases. After strain prioritization, a novel class of CCNP-type glycopeptides named malacinnamycin was identified. A plausible biosynthetic pathway for malacinnamycin was deduced by bioinformatics analysis.

[Selection and validation of reference genes for quantitative real-time PCR analysis in Paeonia veitchii].

Paeonia veitchii and P. lactiflora are both original plants of the famous Chinese medicinal drug Paeoniae Radix Rubra in the Chinese Pharmacopoeia. They have important medicinal value and great potential in the flower market. The selection of stable and reliable reference genes is a necessary prerequisite for molecular research on P. veitchii. In this study, two reference genes, Actin and GAPDH, were selected as candidate genes from the transcriptome data of P. veitchii. The expression levels of the two candidate genes in different tissues(phloem, xylem, stem, leaf, petiole, and ovary) and different growth stages(bud stage, flowering stage, and dormant stage) of P. veitchii were detected using real-time fluorescence quantitative technology(qRT-PCR). Then, the stability of the expression of the two reference genes was comprehensively analyzed using geNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that the expression patterns of Actin and GAPDH were stable in different tissues and growth stages of P. veitchii. Furthermore, the expression levels of eight genes(Pv-TPS01, Pv-TPS02, Pv-CYP01, Pv-CYP02, Pv-CYP03, Pv-BAHD01, Pv-UGT01, and Pv-UGT02) in different tissues were further detected based on the transcriptome data of P. veitchii. The results showed that when Actin and GAPDH were used as reference genes, the expression trends of the eight genes in different tissues of P. veitchii were consistent, validating the reliability of Actin and GAPDH as reference genes for P. veitchii. In conclusion, this study finds that Actin and GAPDH can be used as reference genes for studying gene expression levels in different tissues and growth stages of P. veitchii.

Study on Enhanced Oil Recovery Mechanism of CO2 Miscible Flooding in Heterogeneous Reservoirs under Different Injection Methods.

The mechanism by which oil recovery can be enhanced by different injection methods of CO2 miscible flooding to alleviate the influence of heterogeneous reservoirs was studied to optimize the injection methods, further improving oil recovery. According to the reservoir heterogeneity characteristics of the TI oil formation group in Lunnan Oilfield, a 1 m double-layer long core was designed and prepared for four CO2 miscible displacement experiments with different injection methods. By analyzing the variation in the injection-production parameters, the displacement effects of different injection methods were compared, and the mechanism of enhanced oil recovery (EOR) was summarized. The results indicate the following. ① The displacement efficiency of the different injection methods lies in the following order. Alternate CO2-water injection, continuous CO2 flooding, cyclic CO2 flooding, and alternate CO2-hydrocarbon gas injection. ② The recovery of crude oil via CO2 miscible flooding in heterogeneous reservoirs relies on both convective diffusion and miscible mass transfer. Convective diffusion depends mainly on control of the displacement pressure differential and the plugging of preferential seepage channels in high-permeability areas, while miscible mass transfer depends mainly on the swept range of the convective diffusion and the degree of miscibility between CO2 and crude oil. ③ To improve the recovery efficiency of CO2 miscible flooding in heterogeneous reservoirs, it is necessary to choose an injection method that optimizes these two aspects.

[Quality evaluation of Huocao based on UPLC fingerprint and multi-component content determination].

Huocao(a traditional Chinese herbal medicine) moxibustion is a characteristic technology in Yi medicine suitable for cold-dampness diseases. Huocao, as the moxibustion material, is confusedly used in clinical practice and little is known about its quality control. In this study, UPLC method was used to establish the chemical fingerprint of non-volatile components in Huocao, and the contents of eight phenolic acids such as chlorogenic acid were determined. Multivariate statistical analysis was performed to obtain the indicator components of Huocao for quality evaluation, and thus a comprehensive evaluation system for the quality of Huocao was built. The UPLC fingerprints of 49 batches of Huocao were established, and there were 20 common peaks, of which eight phenolic acids including neochlorogenic acid and chlorogenic acid were identified. Except for three batches of Huocao, the similarity of the other 46 batches was higher than 0.89, suggesting that the established fingerprint method could be used for quality control of the medicinal herb. The correlation coefficient between entropy weight score of the eight phenolic acids and comprehensive fingerprint score in Huocao was 0.875(P<0.01), which indicated that the eight phenolic acids could be used as indicator components for the quality evaluation of Huocao. Furthermore, in multivariate statistical analysis on the common peaks of fingerprint and the contents of the eight phenolic acids, chlorogenic acid, isochlorogenic acid A and isochlorogenic acid C were screened to be the indicator components. The results revealed that the proposed method achieved a simple and accurate quality control of Huocao based on UPLC fingerprint and multi-component content determination, which provided useful data for establishing the quality standard of Huocao.

Microscopic Production Characteristics of Pore Crude Oil and Influencing Factors during Enhanced Oil Recovery by Air Injection in Shale Oil Reservoirs.

High-pressure air injection (HPAI) is one of the effective methods to improve shale oil recovery after the primary depletion process. However, the seepage mechanisms and microscopic production characteristics between air and crude oil are complicated in porous media during the air flooding process. In this paper, an online nuclear magnetic resonance (NMR) dynamic physical simulation method for enhanced oil recovery (EOR) by air injection in shale oil was established by combining high-temperature and high-pressure physical simulation systems with NMR. The microscopic production characteristics of air flooding were investigated by quantifying fluid saturation, recovery, and residual oil distribution in different sizes of pores, and the air displacement mechanism of shale oil was discussed. On this basis, the effects of air oxygen concentration, permeability, injection pressure, and fracture on recovery were studied, and the migration mode of crude oil in fractures was explored. The results show that the shale oil is mainly found in <0.1 µm (small pores), followed by 0.1-1 µm (medium pores), and 1-10 µm (macropores); thus, it is critical to enhancing oil recovery in pores less than 0.1 and 0.1-1 µm. The low-temperature oxidation (LTO) reaction can occur by injecting air into depleted shale reservoirs, which has a certain effect on oil expansion, viscosity reduction, and thermal mixing phases, thereby greatly improving shale oil recovery. There is a positive relationship between air oxygen concentration and oil recovery; the recoveries of small pores and macropores can increase by 3.53 and 4.28%, respectively, and they contribute 45.87-53.68% of the produced oil. High permeability means good pore-throat connectivity and greater oil recovery, and the production degree of crude oil in three types of pores can be increased by 10.36-24.69%. Appropriate injection pressure is beneficial to increasing the oil-gas contact time and delaying gas breakthrough, but high injection pressure will result in early gas channeling, which causes the crude oil in small pores to be difficult to produce. Notably, the matrix can supply oil to fractures due to the mass exchange between matrix fractures and the increase of the oil drainage area, and the recoveries of medium pores and macropores in fractured cores increased by 9.01 and 18.39%, respectively; fractures can act as bridges for matrix crude oil migration, which means that proper fracturing before gas injection can make the EOR better. This study provides a new idea and a theoretical basis for improving shale oil recovery and clarifies the microscopic production characteristics of shale reservoirs.

Wielding the double-edged sword: Redox drug delivery systems for inflammatory bowel disease.

The etiology of inflammatory bowel disease (IBD) is extremely complex and related to an excessive immune response that results in the pathologically release of reactive oxygen species (ROS) via tissue injury and chronic inflammation. Generally, excessive ROS production is one of the essential mediators for inflammatory pathogenesis. Targeting cumulate ROS to interrupt pathological inflammatory responses has been recognized as a feasible strategy for inflammatory suppression of IBD. Correspondingly, the overexpression of ROS can also trigger the drug release of novel drug delivery systems to alleviate IBD symptoms. In this review, we summarized the pathological production of endogenous ROS in IBD, discussed the enormous potential of multiple kinds of ROS-scavenging and ROS-triggering novel delivery systems for the treatment of IBD, including enzymology, metal, polyphenols, natural pigments, nitroxide radicals-contained and sulfide-loaded drug delivery systems, and other novel ROS-responsive materials to synthesize ROS-based drug delivery systems. We also summarized the immunomodulatory effects of ROS-targeted drug delivery systems for the treatment of IBD. Besides, based on the requirements of clinical applications and industrialization development, the challenges faced in the evolution of redox drug delivery systems were also discussed. Collectively, this review provides a reliable reference to the development of ROS-scavenging and ROS-triggering drug delivery systems for the medical intervention of IBD.

[Main components from cultivated and wild Nardostachyos Radix et Rhizoma by LC-MS and GC-MS].

In this study, ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and gas chromatography-mass spectrometry(GC-MS) were combined with non-targeted metabonomic analysis based on multivariate statistics analysis, and the content of five indicative components in nardosinone was determined and compared by UPLC. The main chemical components of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma were comprehensively analyzed. The results of multivariate statistical analysis based on liquid chromatography-mass spectrometry(LC-MS) and GC-MS were consistent. G1 and G2 of the imitative wild cultivation group and G8-G19 of the wild group were clustered into category 1, while G7 of the wild group and G3-G6 of the imitative wild cultivation group were clustered into category 2. After removing the outlier data of G1, G2, and G7, G3-G6 of the imitative wild cultivation group were clustered into one category, and G8-G19 of the wild group were clustered into the other category. Twenty-six chemical components were identified according to the positive and negative ion modes detected by LC-MS. The content of five indicative components(VIP>1.5) was determined using UPLC, revealing that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, linarin, nardosinone, and total content in the imitative wild cultivation group were 1.85, 1.52, 1.26, 0.90, 2.93, and 2.56 times those in the wild group, respectively. OPLS-DA based on GC-MS obtained 10 diffe-rential peaks. Among them, the relative content of α-humulene and aristolene in the imitative wild cultivation group were extremely significantly(P<0.01) and significantly(P<0.05) higher than that in the wild group, while the relative content of 7 components such as 5,6-epoxy-3-hydroxy-7-megastigmen-9-one, γ-eudesmol, and juniper camphor and 12-isopropyl-1,5,9-trimethyl-4,8,13-cyclotetrade-catriene-1,3-diol was extremely significantly(P<0.01) and significantly(P<0.05) lower than that in the wild group, respectively. Therefore, the main chemical components of the imitative wild cultivation group and wild group were basically the same. However, the content of non-volatile components in the imitative wild cultivation group was higher than that in the wild group, and the content of some volatile components was opposite. This study provides scientific data for the comprehensive evaluation of the quality of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma.

[Chemical constituents and anti-liver fibrosis mechanism of Meconopsis quintuplinervia based on UPLC-Q-Exactive-MS/MS and network pharmacology].

In this study, UPLC-Q-Exactive-MS/MS was used to rapidly analyze the chemical constituents of Meconopsis quintupli-nervia, and the anti-liver fibrosis mechanism of M. quintuplinervia was preliminarily analyzed by network pharmacology, molecular docking, and cell experiments. The chemical constituents of M. quintuplinervia were identified according to the information of MS~1 and MS~2, as well as the data in the literature and databases. SwissTargetPrediction and TargetNet were used to predict the potential targets. The targets related to liver fibrosis were collected from GeneCards and OMIM. The protein-protein interaction(PPI) network was constructed by STRING. Cytoscape 3.6.1 was used to construct and analyze the "constituent-target-disease" network to obtain key targets and their corresponding constituents in the network. DAVID 6.8 was used for GO analysis and KEGG signaling pathway enrichment analysis. Finally, the preliminary verification was carried out by molecular docking and cell experiments. As a result, 106 chemical constituents were identified from M. quintuplinervia, including 66 flavonoids, 16 alkaloids, 18 phenolic acids, 1 anthocyanin, and 5 other constituents. Among them, 3 constituents were identified as potential new compounds, and 59 constituents were reported in M. quintuplinervia for the first time. Network pharmacology analysis showed that M. quintuplinervia presumably acted on AKT1, SRC, JUN, EGFR, STAT3, HSP90 AA1, MAPK3, and other core targets through luteolin, isorhamnetin, quercetin, apigenin, kaempferide, amurine, 2-methylflavinantine, allocryptopine, the multi and other active compounds, thereby regulating the PI3 K/AKT signaling pathway, pathways in cancer, proteoglycans in cancer, FoxO signaling pathway, and other pathways to exert anti-liver fibrosis effects. M. quintuplinervia extract(MQE) could significantly down-regulate PI3 K and AKT protein levels in the HSC-T6 cell model induced by TGF-ß1, suggesting that MQE may have the ability to regulate the PI3 K/AKT signaling pathway. The findings of this study indicated that the anti-liver fibrosis effect of M. quintuplinervia had multi-constituent, multi-target, and multi-pathway characteristics, which may provide a scientific basis for the research on the pharmacodynamic materials, action mechanism, and quality markers of M. quintupli-nervia.

[UPLC fingerprint and indicator components of Boenninghausenia albiflora var. albiflora].

The fingerprint of Boenninghausenia albiflora var. albiflora was established by ultra performance liquid chromatography(UPLC), and the content of 12 active components including chlorogenic acid was determined. Multivariate statistical analysis was used to explore the indicator components of B. albiflora var. albiflora and a comprehensive evaluation system was created for the quality of B. albiflora var. albiflora. In this study, 33 batches of B. albiflora var. albiflora with different sources were collected and studied, and the UPLC fingerprint of B. albiflora var. albiflora was developed. There were 37 common peaks, of which 12 components were identified, and the content of these 12 components was measured. In combination of the common peaks and the content of chemical components, multivariate statistical analysis was performed, and the results showed that 6 components [daphnoretin, isoimperatorin, astragalin, imperatorin, neochlorogenic acid, and isoquercitrin(weight coefficient>0.1)] were selected as chemical markers for the quality of B. albiflora var. albiflora. Technique for order of preference by similarity to ideal solution(TOPSIS) analysis and chemometrics revealed that the quality of S32, S28 and S29 were superior, while that of S12, S7 and S16 were inferior. The quality evaluation method of B. albiflora var. albiflora constructed in this study was accurate and reliable, with simpleness and easiness to operate. It is suggested that the 6 above-mentioned active components could be used as indicator components for quality control of B. albiflora var. al-biflora. The samples were harvested during the flowering and fruiting period, which is from the beginning of July to the end of August.

MerTK-mediated efferocytosis promotes immune tolerance and tumor progression in osteosarcoma through enhancing M2 polarization and PD-L1 expression.

The poor progress of immunotherapy on osteosarcoma patients requires deeper delineation of immune tolerance mechanisms in the osteosarcoma microenvironment and a new therapeutic strategy. Clearance of apoptotic cells by phagocytes, a process termed "efferocytosis," is ubiquitous in tumors and mediates the suppression of innate immune inflammatory response. Considering the massive infiltrated macrophages in osteosarcoma, efferocytosis probably serves as a potential target, but is rarely studied in osteosarcoma. Here, we verified M2 polarization and PD-L1 expression of macrophages following efferocytosis. Pharmacological inhibition and genetic knockdown were used to explore the underlying pathway. Moreover, tumor progression and immune landscape were evaluated following inhibition of efferocytosis in osteosarcoma model. Our study indicated that efferocytosis promoted PD-L1 expression and M2 polarization of macrophages. Ëfferocytosis was mediated by MerTK receptor in osteosarcoma and regulated the phenotypes of macrophages through the p38/STAT3 pathway. By establishing the murine osteosarcoma model, we emphasized that inhibition of MerTK suppressed tumor growth and enhanced the T cell cytotoxic function by increasing the infiltration of CD8+ T cells and decreasing their exhaustion. Our findings demonstrate that MerTK-mediated efferocytosis promotes osteosarcoma progression by enhancing M2 polarization of macrophages and PD-L1-induced immune tolerance, which were regulated through the p38/STAT3 pathway.

[Randomized controlled trial on cervical spondylotic radiculopathy of wind-cold-damp type treated with acupuncture and thunder-fire moxibustion].

OBJECTIVE: To explore the therapeutic effect of acupuncture combined with thunder-fire moxibustion on cervical spondylotic radiculopathy of wind-cold-damp type and its impacts on the conduction velocity of F wave of median nerve and ulnar nerve, as well as hypersensitive C-responsive protein (hs-CRP), interleukin 6 (IL-6), IL-1ß and tumor necrosis factor α (TNF-α) in serum. METHODS: A total of 94 patients with cervical spondylotic radiculopathy of wind-cold-damp type were randomly divided into a control group and a combined therapy group, 47 cases in each group. In the control group, acupuncture was applied to Fengchi (GV20), Tianzhu (BL10), Neck-Jiaji (EX-B5), Dazhui (GV14) and others, 30 min each time, once daily, 5 times a week, totally for 4 weeks. In the combined therapy group, on the base of the treatment as the control group, the thunder-fire moxibustion was adopted over GV20, EX-B5, GV14, Jianjing (ST21) and Tianzong (SI11), 20 min each time, once every other day, for 4 weeks in total. After the treatment, the curative effect was compared in the patients between two groups. The short-form McGill pain questionnaire (SF-MPQ), the neck specificity scale and the MOS 36-item short form health survey (SF-36) were scored. The conduction velocity of F wave in median nerve and ulnar nerve was detected by electromyography. The expression of hs-CRP was measured by immunoturbidimetry. IL-6, IL-1ß and TNF-α in serum were determined by enzyme linked immunosorbent assay. RESULTS: The total effective rate in the combined therapy group was 95.7% (45/47), which was higher than 80.9% (38/47) in the control group (P<0.05). Compared with their own pretreatment, the scores of SF-MPQ, neck specificity scale and SF-36 were all obviously improved after treatment in the patients of either group (P<0.05), while the conduction velocity of F wave in median nerve and ulnar nerve was accelerated and hs-CRP, IL-6, IL-1ß and TNF-α in serum were decreased (P<0.05). Compared with the control group, the improvements in the scores of SF-MPQ, neck specificity scale and SF-36 were more obvious (P<0.05), the increase of the conduction velocity of F wave in median nerve and ulnar nerve and the decrease of hs-CRP, IL-6, IL-1ß and TNF-α in serum were more remarkable (P<0.05) in the combined therapy group. CONCLUSION: Acupuncture combined with thunder-fire moxibustion relieves the clinical symptoms of cervical spondylotic radiculopathy of wind-cold-damp type.

Research on Characterization and Heterogeneity of Microscopic Pore Throat Structures in Tight Oil Reservoirs.

The key to the efficient development of a tight reservoir is its accurate evaluation. In this study, the pore throat structure characteristics of sandstone samples in the study block were analyzed by high-pressure mercury injection technology. According to the characteristics of the capillary pressure curve, the sandstone samples in the study block were divided into three types: the first type has a reservoir permeability greater than 0.7 mD and a core mercury injection saturation of 96% with a good reservoir quality; the second type has a reservoir permeability ranging from 0.4 to 0.7 mD and a core mercury injection saturation of 80% with a moderate reservoir quality; and the third type has a reservoir permeability between 0.1 and 0.4 mD and a core mercury injection saturation of 50% with a poor reservoir quality. Also, high-resolution synchrotron radiation imaging and scanning electron microscopy were used to observe the pore throat structure, connectivity, and microscopic heterogeneity of sandstone samples, showing an increasing level of pore disconnection, serious microscopic heterogeneity, and poor reservoir performance as reservoir permeability declines. As mineral composition tests show, the lithology of the tight sandstone in the target block is mainly medium-grained and fine-grained feldspar lithic sandstone and the longitudinal heterogeneity of lithology and mineral components of tight sandstone is relatively weak at above the centimeter level. Besides, based on the high-pressure mercury injection test data, fractal theory is applied to calculate the fractal dimensions of the three types of reservoirs. The result shows a gradual increase in fractal dimensions with the decrease of reservoir quality, in which the closer the fractal dimension is to 3, the more serious the microscopic heterogeneity is, and the stronger the roughness of the pore surface is. As a result, the more heterogeneous the tight reservoir gets, the more likely the injected fluid is to flow along the developed and connected pore regions.