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The Shuitoushan Pb–Zn deposit, which is located in the southern Baoshan Block of Sanjiang region, SW China, forms an important part of the Luziyuan polymetallic ore field. The origin of ore‐forming fluids and the genesis of this deposit are rarely reported. In this study, we present the results of geological features, fluid‐inclusion and isotopic (O, S, Pb) analyses of the Shuitoushan deposit. The mineralization process of this deposit can be divided into three stages: pyrite‐quartz stage (Stage I), sphalerite‐galena‐chalcopyrite stage (Stage II), and chalcopyrite‐calcite stage (Stage III), with a relatively medium‐low temperature (their homogenization temperatures ranging from 261 to 340°C, 219 to 300°C, and 159 to 225°C, respectively) and low salinity (their salinities varying from 2.1 to 6.8 wt% NaCleqv., 1.2 to 4.9 wt% NaCleqv. and 0.7 to 3.85 wt% NaCleqv., respectively), as revealed by microthermometry study of three types of fluid inclusions, namely L‐type (liquid‐rich), V‐type (vapor‐rich), and PL‐type (pure liquid), distinguished in ore‐bearing quartz veins. The decline of δ18OH2O values (decreasing from 7.58‰ in early stage to 0.08‰ in late stage) of the mineralizing fluid indicates an initial magmatic water source of it, with a gradually increasing input of meteoric water during the process of evolution. The ore‐forming materials are likely to be mainly derived from the concealed intermediate‐acid intrusions and also wall rocks, as suggested by the δ34S values (4.1–12.2‰) and Pb isotope compositions (206Pb/204Pb = 18.325–18.448, 207Pb/204Pb = 15.806–15.944, 208Pb/204Pb = 38.822–39.439) of sulphides in ores. Above all, the Shuitoushan deposit can be classified as an epithermal Pb–Zn deposit. This study also indicates that the Pb–Zn polymetallic deposits in the Luziyuan ore field have similar ore‐forming fluids and materials sources, the distribution and mineralization process of which are controlled by the concealed intermediate‐acid intrusion at depth in Luziyuan, Wumulan, and Shuitoushan areas. [ABSTRACT FROM AUTHOR]

JLX001, a novel compound with similar structure with cyclovirobuxine D (CVB-D), has been proved to exert therapeutical effects on permanent focal cerebral ischemia. However, the protective effects of JLX001 on cerebral ischemia/reperfusion (I/R) injury and its anti-apoptotic effects have not been reported. We investigated the efficacy of JLX001 in two pharmacodynamic tests (pre-treatment test and post-treatment) with rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). The pharmacodynamic tests demonstrated that JLX001 ameliorated I/R injury by reducing infarct sizes and brain edema. The results of Morris water maze, neurological scores, cylinder test and posture reflex test implied that JLX001 improved the learning, memory and motor ability after MCAO/R in the long term. Anti-apoptotic effects of JLX001 and its regulation of cytosolic c-Jun N-terminal Kinases (JNKs) signal pathway were confirmed in vivo by co-immunofluorescence staining and western immunoblotting. Furthermore, primary cortical neuron cultures were prepared and exposed to oxygen glucose deprivation/reoxygenation (OGD/R) for in vitro studies. Cytotoxicity test and mitochondrial membrane potential (MMP) test showed that JLX001 enhanced cell survival rate and maintained MMP. Flow cytometry and TdT-mediated dUTP-X nick end labeling (TUNEL) staining demonstrated the anti-apoptotic effects of JLX001 in vitro. Likewise, JLX001 regulated JNK signal pathway in vivo, which was also confirmed by western immunoblotting. Collectively, this study presents the first evidence that JLX001 exerted protective effects against I/R injury by reducing neuronal apoptosis via down-regulating JNK signaling pathway. • JLX001 attenuated cerebral ischemia/reperfusion injury in MCAO/R rats. • JLX001 inhibited neuronal apoptosis in MCAO/R rats and OGD/R neurons. • JLX001 down-regulated MAPK/JNK signal both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine(TCM) single preparation refers to the innovative TCM made from the whole or the effective part(including the effective ingredient) extract of a TCM single herb by modern technology. They have a long history of applications, definite effects and few side effects. It is an indispensable part of the research of innovative TCM. In recent years, with the optimization of national policies, the development of TCM single preparation shows a positive trend. However, because of the imbalance in the composition ratio, the need for expansion of indications, the need for further basic research, and the low conversion rate of existing patent achievements in universities and institutes, the TCM single preparation still has significant development space. In this review, we analyze and study the current situation, characteristics and difficulties of TCM single preparation, as well as relevant clinical application, basic research, industrialization and patent application information through statistical analysis of TCM single preparations in the Chinese Pharmacopoeia, which helps to provide direction for the development and research of single preparation of TCM.

Objective: To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM)., Methods: The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34 + cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens., Results: The 41 patients underwent 97 mobilization collections, and the median number of CD34 + cells collected was 6.09 (0-34.07)×10 6 /kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34 + cells collected and acquisition success rate ( P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34 + cell count ( P <0.05). The PXF+G-CSF group had a larger number of CD34 + cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased ( P <0.05)., Conclusion: PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34 + cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.

Objective: To explore and design a novel bi-specific chimeric antigen receptor (CAR) structure. To obtain the corresponding CAR-T cells and verify killing effects on tumor cells in vitro and in vivo., Methods: Five kinds of bi-specific CAR structures including humanized CD19 scFv and CD79b scFv, CD8 hinge & TM-4-1BB-CD3ζ and/or CD3ε chain intracellular regions were constructed and prepared. CAR-19-79b cells were obtained. Five kinds of CAR-T cells were co-incubated with the 3M-CD19-CD79b-Luc target cells. Luciferase assay and ELISA were used to detecte the killing ability of these five groups of CAR-T cells and the secretion of cytokines and compared. The optimal structure of CAR-T cells was used to treat the leukemia mouse model constructed by Daudi-Luc cells. And the treatment efficacy was evaluated. At the same time, other targets were used in this structure. With the same methods, the stability and effectiveness of the structure were verified., Results: CAR-19-79b-T cells were cultured for 7 days, the expression rates of CAR-19 and CAR-79b were 21.6%-36.3% and 21.7%-37.8%, respectively. The killing rates of 5 kinds of CAR-19-79b-T cells prepared by T cells from 3 healthy donors on 3M-CD19-CD79b-Luc cells were significantly higher than those of the T cell control group at the effect-target ratio of 10∶1. Among them, the killing rates of CAR-19-79b-T cells with No. III and No. IV structures were the strongest. After co-incubation with 3M-CD19-CD79b-Luc target cells, the amount of IFN-γ and TNF-α secreted by CAR-T cells with CAR IV and CARV structures was the lowest. And there was no significance between the two groups ( P >0.05). CAR IV cells with remarkable killing effect and low secretion factor had obvious therapeutic effect on Daudi-Luc leukemia mice, extending the survival period of mice to 64 days. And all mice in the T cell control group died at 41.0±2.4 days. The CAR-19-BCMA-T and CAR-19-22-T with the same structure showed significant killing ability and low cytokine expression levels., Conclusion: A novel bi-specific CAR structures was successfully designed, which could efficiently kill the corresponding tumor cells and secrete less cytokines (such as TNF-α, IFN-γ). Moreover, it shows obvious therapeutic effect on Daudi lymphoma mouse model. The bi-specific CAR structure shows good killing specificity and safety.

A facile and versatile method for generating radicals from Csp 3 -H bonds under metal-free and organic-peroxide-free conditions was developed. By combining safe persulfate and low-toxic quaternary ammonium salt, a wide variety of Csp 3 -H compounds including ethers, (hetero)aromatic/aliphatic ketones, alkylbenzenes, alkylheterocycles, cycloalkanes, and haloalkanes were selectively activated to generate the corresponding C-centered radicals, which could be further captured by N -arylacrylamides to deliver the valuable functionalized oxindoles. Good functional group tolerance was demonstrated. The useful polycarbonyl compound and esters were also modified with the strategy. Moreover, the combination can also be applied to the practical coupling between simple haloalkanes and N -hydroxyphthalimide (NHPI).

Short tandem repeat (STR) markers have been widely used in forensic paternity testing and individual identification, but the STR mutation might impact on the forensic result interpretation. Importantly, the STR mutation rate was underestimated due to ignoring the "hidden" mutation phenomenon in most similar studies. Considering this, we use Slooten and Ricciardi's restricted mutation model based on big data to obtain more accurate mutation rates for each marker. In this paper, the mutations of 20 autosomal STRs loci (D3S1358, D1S1656, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D6S1043, D7S820, D5S818, TPOX, D8S1179, D12S391, D19S433, and FGA; The restricted model does not include the correction factor of D6S1043, this paper calculates remaining 19 STR loci mutation rates) were investigated in 28,313 (Total: 78,739 individuals) confirmed parentage-testing cases in Chinese Han population. As a result, total 1665 mutations were found in all loci, including 1614 one-steps, 34 two-steps, 8 three-steps, and 9 nonintegral mutations. The loci-specific average mutation rates ranged from 0.00007700 (TPOX) to 0.00459050 (FGA) in trio's and 0.00000000 (TPOX) to 0.00344850 (FGA) in duo's. We analyzed the relationship between mutation rates of the apparent and actual, the trio's and duo's, the paternal and maternal, respectively. The results demonstrated that the actual mutation rates are more than the apparent mostly, and the values of μ1"/μ2"(apparent) are also greater than μ1/μ2 (actual) commonly (μ1", μ1; μ2", μ2 are the mutation rates of one-step and two-step). Therefore, the "hidden" mutations are identified. In addition, the mutations rates of trio's and duo's, the paternal and maternal, exhibit significant difference. Next, those mutation data are used to do a comparison with the studies of other Han populations in China, which present the temporal and regional disparities. Due to the large sample size, some rare mutation events, such as monozygotic (MZ) mutation and "fake four-step mutation", are also reported in this study. In conclusion, the estimation values of actual mutations are obtained based on big data, they can not only provide basic data for the Chinese forensic DNA and population genetics databases, but also have important significance for the development of forensic individual identification, paternity testing and genetics research.

The high shear wet granulation(HSWG) process of Chinese medicine has a complicated mechanism. There are many influencing factors that contribute to this process. In order to summarize the manufacturability of different kinds of materials in HSWG, this paper constructed a material library composed of 11 materials, including 4 Chinese medicine extracts and 7 pharmaceutical excipients. Each material was described by 22 physical parameters. Several binders were employed, and their density, viscosity and surface tension were characterized. Combining empirical constraints and the principle of randomization, 21 designed experiments and 8 verification experiments were arranged. The partial least squares(PLS) algorithm was used to establish a process model in prediction of the median granule size based on properties of raw materials and binders, and process parameters. The surface tension and density of binders, as well as the maximum pore saturation were identified as key variables. In the latent variable space of the HSWG process model, all materials could be divided into three categories, namely the Chinese medicine extracts, the diluents and the disintegrants. The granulation of Chinese medicine extracts required low viscosity and low amount of binder, and the resulted granule sizes were small. The diluent powders occupied a large physical space, and could be made into granules with different granule sizes by adjusting the properties of binders. The disintegrants tended to be made into large granules under the condition of aqueous binder. The combination use of material database and multivariate modeling method is conducive to innovate the knowledge discovery of the wet granulation process of Chinese medicine, and provides a basis for the formulation and process design based on material attributes.

In this study, the effects of exogenous abscisic acid (ABA) on the growth and physiolo-gical characteristics of Machilus yunnanensis seedlings were examined under well water supply conditions (70%-75% field capacity, FC) and different drought stress conditions, i.e., light drought stress (50%-55% FC) and severe drought stress (30%-35% FC), respectively. The results showed that drought stress reduced leaf relative water content, plant height, and total biomass of seedlings significantly decreased, as well as net photosynthetic rate and maximal photochemistry efficiency (F v /F m ), but enhanced root/shoot and malondialdehyde contents (MDA). Exogenous ABA improved the adaptability of seedlings under drought stress, especially under severe drought stress, with leaf relative water content being improved 21.0%. Plant height and biomass allocation were improved by exogenous ABA under drought, while root/shoot was improved by 1.1 times compared with the well watered plants. The accumulation of MDA was decreased, the activities of CAT and SOD were significantly increased, and the proline content was increased 6.7 times by exogenous ABA under drought. Exogenous ABA application alleviated the negative effect of drought on photosynthetic organs, reduced the decrease of net photosynthetic rate and stomatal conductance under drought, and enhanced F v /F m value. The results suggested that exogenous ABA treatment could enhance the resistance of M. yunnanensis to drought stress.