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Background: Universally accepted fixative is 10% formalin which has been used for preserving the tissues and their architecture. In certain conditions, formalin might not be readily available for immediate fixation. We here by explore more economical, ecofriendly and easily available solutions that can be used as transit media/ transporting media for tissue specimens. Materials and Methods: The study included commonly available solutions like Spirit, Saline, Betadine solution, Hydrogen peroxide (H2 O2 ), Local anesthesia (L.A), Rose water, Coconut oil, Coconut water, Ice cold water, Honey and Milk while keeping formalin as control. The fresh tissue sample was cut into multiple bits and placed in different containers for a period of 8 hours before transferring to formalin solution. Conclusion: Transit fixatives are very important in certain situations where formalin is not readily available. These fixatives can be used to fix the tissues for a period of at least 8 hours without causing any damage or distortion before they are fixed in formalin solution.

Macrocyclic conformations play a crucial role in regulating their properties. Our understanding of the determinants to control macrocyclic conformation interconversion is still in its infancy. Here we present a macrocycle, octamethyl cyclo[4](1,3-(4,6)-dimethylbenzene)[4]((4,6-benzene)(1,3-dicarboxylate) (OC-4), that can exist at 298 K as two stable atropisomers with C 2v and C 4v symmetry denoted as C 2v -OC-4 and C 4v -OC-4, respectively. Heating induces the efficient stepwise conversion of C 2v - to C 4v -OC-4 via a C s -symmetric intermediate (C s -OC-4). It differs from the typical transition state-mediated processes of simple C-C single bond rotations. Hydrolysis and further esterification with a countercation dependence promote the generation of C 2v - and C s -OC-4 from C 4v -OC-4. In contrast to C 2v -OC-4, C 4v -OC-4 can bind linear guests to form pseudo-rotaxans, or bind C 60 or C 70 efficiently. The present study highlights the differences in recognition behavior that can result from conformational interconversion, as well as providing insights into the basic parameters that govern coupled molecular rotations., (© 2024. The Author(s).)

Aim: The current research set out to examine and contrast the amounts of apically extruded debris produced by two distinct rotary files and hand files used in pulpectomy procedures., Materials and Methods: Forty-five extracted primary mandibular molars were randomly divided into three groups for instrumentation. Prime Pedo™ files are in Group 1, DXL-Pro Pedo files are in Group 2, and H and K files are in Group 3. Debris that had been apically extruded and collected in preweighed Eppendorf tubes was incubated for five days at 70°C. The weight of the Eppendorf tubes before and after instrumentation was subtracted to get the weight of the debris that was gathered., Results: It was noted that all three groups had significantly different amounts of material ejected from the tip. The groups with the lightest amounts of extruded debris were 1, 2, and 3, in that order. The most debris was extruded from the apex in Group 3., Conclusion: This suggests that rotary files are preferable to hand files because they reduce debris extrusion, which in turn reduces postoperative events following pulpectomy procedures., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Background: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival., Methods: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs., Results: K17 expression had profound effects on the exclusion of intratumoral CD8+ T cells and was also associated with decreased numbers of peritumoral CD8+ T cells, CD16+ macrophages, and CD163+ macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8+ T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations., Conclusions: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer., (© 2024. The Author(s).)

Molecular folding regulation with environmental stimuli is critical in living and artificial molecular machine systems. Herein, we described a macrocycle, cyclo[4] (1,3-(4,6-dimethyl)benzene)[4](1,3-(4,6-dimethyl)benzene)(4-pyridine). Under 298 K, it has three stable stiff atropisomers with names as 1 (C s symmetry), 2 (C s symmetry), and 3 (C 4v symmetry). At 393 K, 1 can reversibly transform into 2, but at 473 K, it can irrevocably transform into 3. At 338 K, 3 and (PhCN) 2 PdCl 2 complex to produce the metal-organic cage 4. Only at 338 K does the combination of 1 or 2 and (PhCN) 2 PdCl 2 create a gel-like structure. Heating both gels to 473 K transforms them into 4. In addition to offering a thermally accelerated method for modifying self-assembled systems using macrocyclic building blocks, this study also has the potential to develop the nanoscale transformation material with a thermal response., (© 2023. The Author(s).)

Climate warming and thawing of permafrost in the Qinghai-Tibet Plateau have resulted in soil erosion and the decline of soil quality. Determining the decadal variation of soil quality in the Qinghai-Tibet Plateau is the basis for scientific understanding of soil resources and the key to vegetation restoration and ecological reconstruction. In this study, we used eight indicators (including soil organic matter, total nitrogen, and total phosphorus) to eva-luate soil quality of montane coniferous forest zone (Tibet's natural geographical division zone Ⅱ) and montane shrubby steppe zone (zone Ⅳ) by calculating soil quality index (SQI) in the southern Qinghai-Tibet Plateau in the 1980s and 2020s. Variation partitioning (VPA) was used to examine the drivers for the heterogeneity of the spatial-temporal distribution of soil quality. The results showed that soil quality in each natural zone showed a downward trend in the past 40 years, with SQI of zone Ⅱ decreasing from 0.505 to 0.484 and that of zone Ⅳ decreasing from 0.458 to 0.425. The spatial distribution of soil nutrients and quality was heterogeneous, while soil nutrient conditions and quality in zone Ⅱ were better than those in zone Ⅳ in different periods. The VPA results indicated that the interaction of climate change, land degradation, and vegetation differences was the major cause of temporal variation in soil quality. Differences in climate and vegetation could better explain the spatial variation of SQI.

Aims: Tobacco (Nicotiana tabacum) is an economically important crop. Root rot caused by Fusarium oxysporum has become a damaging disease in N. tabacum crops grown in Henan province of China. Therefore, the objectives of this study were to screen bacterial isolates against F. oxysporum from rhizosphere soils of tobacco growing areas and to evaluate their antifungal activities, biocontrol effects, and effects on plant growth., Methods and Results: Nineteen strains with antifungal inhibition effects of >60% against F. oxysporum were obtained using the method of flat confrontation; the strain Ba-0321 was the strongest, with an antifungal effect of 75%. Moreover, this strain had broad spectrum antimicrobial activity to eight additional tobacco pathogens. The strain was identified as Bacillus velezensis by morphology and the 16S rDNA sequence. The B. velezensis strain Ba-0321 had strong UV resistance as well as tolerance to high temperatures and low nutrition. The bacteria inhibited spore germination and mycelial growth of F. oxysporum under in vitro co-culture conditions. In vivo assays demonstrated that the Ba-0321 strain significantly reduced the pathogenicity of F. oxysporum, resulting in a control effect on tobacco root rot of 81.00%. Simultaneously, the bacteria significantly promoted root development and the growth of tobacco plants., Conclusion: Our results confirmed that the B. velezensis strain Ba-0321 has a strong antifungal effect and stress resistance that enable it to be used as a biological control agent for tobacco root rot caused by F. oxysporum., Significance and Impact of the Study: Tobacco root rot caused by F. oxysporum has become a damaging disease in China. The B. velezensis strain Ba-0321 has promising application value for controlling tobacco root rot diseases, and it could provide a new biocontrol agent against root rot caused by F. oxysporum in other plant species., (© The Author(s) 2022. Published by Oxford University Press on behalf of Applied Microbiology International.)

Background: Hepatocellular carcinoma (HCC) remains one of the most common and lethal malignancies worldwide. Although DBF4-dependent kinase (DDK) complex composed of CDC7 kinase and its regulatory subunit DBF4 has been shown to be overexpressed in primary tumors and promotes tumor development, while its role and prognostic value in HCC remain largely unknown. In the present study, the expression of DBF4 and CDC7 and their relationship with clinical characteristics were comprehensively analyzed., Methods: The mRNA expression profiles of HCC and the corresponding clinical data of HCC patients were downloaded from TCGA and GEO databases, respectively. The differences in DBF4 and CDC7 expression in tumor tissues and adjacent normal tissues were analyzed. HCC-derived tissue microarray (TMA) was used to evaluate and score the expression of CDC7 by immunohistochemistry (IHC) staining. The Kaplan-Meier method and the Cox regression method were used to analyze the relationship between overall survival and clinical characteristics of the patients. Gene set enrichment analysis (GSEA) was used to analyze the pathway enrichment of DBF4 and CDC7., Results: DBF4 and CDC7 had similar expression patterns in HCC patients. Detailly, compared with adjacent tissues, both mRNA and protein of DBF4 and CDC7 were significantly higher in HCC, and their expression was positively correlated with AJCC&#95;T stage, clinical stage and G stage (grade) of liver cancer patients, and higher DBF4 or CDC7 expression predicted a worse prognosis in HCC patients with shorter overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS) and progress-free survival (PFS). Cox regression analysis suggested that both DBF4 and CDC7 were independent risk factors for the prognosis of HCC patients in TCGA dataset. GSEA suggested that both DBF4 and CDC7 were positively correlated with cell cycle and DNA replication. Finally, the prognostic value of CDC7 was furtherly confirmed by TMA-based IHC staining results., Conclusions: Our study showed that DDK complex was significantly increased in HCC. Both DBF4 and CDC7 may be potential diagnostic and prognostic markers for HCC, and high expression of DDK members predicts a worse prognosis in patients with HCC, which may be associated with high tumor cell proliferation rate., (© 2022. The Author(s).)

Development of a stereoselective asymmetric catalytic system with high conversion is the key to success for acquiring chiral materials. In recent years, DNA hybrid catalysts have attracted significant interest due to their excellent abilities in accelerating reactions and achieving high enantioselectivity. We report here that bipyridine linked with polyamide as a sequence-specific catalytic ligand was designed to perform a DNA hybrid asymmetric reaction. The products presented different stereoselectivities compared to the results of reactions catalyzed by bipyridine. Comparing catalytic experiments based on alternative oligonucleotides verified that sequence-locating of the ligand affected the catalytic microenvironment. Circular dichroism spectra, combined with singular value decomposition, proposed that different binding modes could exist somewhere between the ligand and alternative sequences. The current work provides a strategy to extend the chemical range of DNA-based catalysis.

Snowpit samples of three glaciers (Laohugou NO. 12 Glacier (LHG), Small Dongkemadi Glacier on Mount Tanggula (TGL) and East Ronghuk Glacier on Mount Everest (ZF)) in the Tibetan Plateau were collected. Concentrations of DOC and major ions were analyzed. The results showed that average DOC concentrations of the snowpits of LHG, TGL and ZF were (250.30 +/- 157.10), (216.92 +/- 142.82) and (152.50 +/- 56.11) microg x L(-1), respectively. DOC of TGL and ZF accounted for large parts of total values of DOC and ions. Correspondingly, DOC of LHG accounted for small part (only 5%), because LHG was located at north China and intensively influenced by natural mineral dust, which caused high concentrations of Ca2+ (the highest value could reach 5299.18 microg x L(-1)) and consequently low percentage of DOC of snowpit samples. Correlation and PCA analyses were used to study the sources of DOC. DOC was significantly correlated with Ca2+, Mg2+, K+ and SO4(2-). Additionally, PCA further indicated that the main potential source of DOC was the natural source of mineral dust. Meanwhile, anthropogenic pollutants (e.g., biomass, fossil combustion and agricultural related pollutants) could also not be ignored. Moreover, the carbon depositional fluxes of three snowpits were roughly estimated, and the values of LHG, TGL and ZF snowpits were 189.23, 132.76 and 128.44 mg (m2 x a)(-1), respectively, which played a significant role in the carbon cycle in this region and was also helpful for the study of glaciers fluctuation.

The well-characterized anti-tubulin agent, podophyllotoxin (PTOX), with the 4'-position methoxyl group, targets the colchicines domain located between α- and β-tubulin. Two guanosine triphosphate (GTP) analogs of the tubulin-binding region were synthesized from PTOX, where a hydroxyl group was substituted with a carbon-sulfur bond. These compounds, 4-MP-PTOX and 4-TG-PTOX, reduce the dosage and greatly improve the therapeutic effect for microtubule damage in cancer cells. Here we characterize the anti-tubulin properties of these compounds. We found the stronger inhibition of tubulin polymerization (the concentration of 50% growth inhibition, GI50<2 μM) for compounds 4-TG-PTOX and 4-MP-PTOX, which were better than that of PTOX or colchicine. The cytotoxicity of two designed compounds on tumor cells was also significantly enhanced by comparing to those of PTOX and colchicines. The ΔH value of 4-MP-PTOX and 4-TG-PTOX binding to tubulin by isothermal titration calorimetry (ITC) was found to be -7.4 and -5.3 kcal·mol(-1), respectively. The wide range of enthalpy values across the series may reflect entropy/enthalpy compensation effects. Fragments 6-mercaptopurine (MP) and 6-thioguanine (TG) likely enhance the affinity of 4-MP-PTOX and 4-TG-PTOX binding to tubulin by increasing the number of binding sites. The correctness of rational drug design was strictly demonstrated by a bioactivity test.

Nine heavy metals (Cd, Co, Ni, Cu, Zn, Pb, Cs, As, Cr) of surface sediments collected from the Middle Part of the Yarlung Zangbo River were analyzed by BCR sequential extraction procedure. Based on speciation distributions of these metals, ecological risk of heavy metals was assessed with methods of risk assessment code (RAC) and sediment quality guideline quotient (SQG-Q). The results show that: (1) Large part of Cr and As belong to residual fraction(87%-96%). Ni, Cu, Co and Cs have similar distribution characteristics (non-residual part accounts for approximate 20%). Correspondingly, mass fraction of Cd exists mainly in acid soluble and reducible faction (65% ) , indicating high ecological risk level. (2) Based on calculation of RAC method, Cd is of high risk to the environment (37. 38%). Accordingly, Co, Ni, Cu and Zn are of low risk, and Pb, Cs, As and Cr pose extreme low risk to the environment. According to evaluation of heavy metal speciation distributions, the potential ecological risk of heavy metals is in the descending order of Cd > Co > Ni > Cu > Zn > Pb > Cs > As > Cr. (3) The SQG index of sediments is 0. 804, indicating that studied river sediment has a moderate potential biological toxicity effect. Given most of heavy metals exists in residual fraction, the sediments of this region pose a low ecological risk to the environment.

Hoh Xil locates at northern part of the Tibetan Plateau. Twenty five surface soil samples were collected from this area in 2007 and 32 elements were analyzed and compared to the element contents of Yarlung Zangbo river sediment, background element value of the Tibetan surface soil and the Chinese Continental crust contents. The results showed that the element contents of the < 20 microm fraction were higher than those of bulk samples; Contents of many elements of this study were similar to those of the Tibetan soil. Meanwhile, contents of Ca and As of the studied area were higher than those of Chinese continental crust, resulting mainly from local alpine arid climate and widely distributed the rocks that enriched in As, respectively. The EOF analysis of the contents of bulk soil samples revealed the sources and chemical properties of studied elements: many elements such as Al, Fe, Ga inherit the characteristics of the parent rocks of this region. Meanwhile, elements with an active chemical property and the element Zr that specially existed in the heavy minerals also had a certain contribution to the contents. The contents of B and Cs revealed contribution of hot springs to the soil of studied area.

According to the structure-function relationship of podophyllotoxin (PTOX) and its analogue of 4'- demethylepipodophyllotoxin (DMEP), the 4 β-substitution of sulfur-containing heterocyclic compounds with a carbon-sulfur bond at 4 position of PTOX or DMEP is an essential modification direction for improving the anti-tumor activity. So, four novel 4 β-sulfursubstituted podophyllum derivatives (i.e., 4β -(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MT-PTOX), 4β-(1,3,4- thiadiazole-2-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MTD-PTOX), 4β-(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-4' -demethylepipodophyllotoxin (4-MT-DMEP), and 4β-(1,3,4-thiadiazole-2-yl)sulfanyl-4-deoxy-4'-demethylepipodophyllotoxin (4-MTD-DMEP)) were designed and then successfully biosynthesized in this work. In the novel sulfur-substituted biotransformation processes, PTOX and DMEP was linked with sulfur-containing compounds (i.e., 3-mercapto-1,2,4-triazole (MT) and 2-mercapto-1,3,4-thiadiazole (MTD)) at 4 position of cycloparaffin to produce 4-MT-PTOX (1), 4-MTD-PTOX (2), 4-MT-DMEP (3), and 4-MTD-DMEP (4) by Penicillium purpurogenum Y.J. Tang, respectively, which was screened out from Diphylleia sinensis Li (Hubei, China). All the novel compounds exhibited promising in vitro bioactivity, especially 4-MT-PTOX (1). Compared with etoposide (i.e., a 50 % effective concentration [EC(50)] of 25.72, 167.97, and 1.15 M), the EC(50) values of 4-MT-PTOX (1) against tumor cell line BGC-823, A549 and HepG2 (i.e., 0.28, 0.76, and 0.42 M) were significantly improved by 91, 221 and 2.73 times, respectively. Moreover, the EC(50) value of 4-MT-PTOX (1) against the normal human cell line HK-2 (i.e., 182.4 μM) was 19 times higher than that of etoposide (i.e., 9.17 μM). Based on the rational design, four novel 4 β-sulfur-substituted podophyllum derivatives with superior in vitro anti-tumor activity were obtained for the first time. The correctness of structure-function relationship and rational drug design was strictly demonstrated by the in vitro biological activity tests.