Evolution of fermented grain yeast communities in strong-flavored baijiu and functional validation of yeasts that produce superior-flavored substances.

BACKGROUND: Baijiu is a well-known alcoholic beverage in China and the quality is determined by various microorganisms during the fermentation process. Yeast is one of the most important microorganisms in the fermentation of baijiu. It has a strong esterification capacity and also affects the aroma. RESULTS: High-throughput sequencing results showed that the fermented grains (jiupei) during baijiu production were mainly composed of eight highly abundant yeast species. The species and abundance of yeasts changed significantly with the fermentation process. The flavor of 30 yeast strains in the jiupei was determined by a sniffing test and gas chromatography-mass spectrometry (GC-MS). The strain with the highest flavor substance content (2.34 mg L-1 ), named YX3205, was identified as Clavispora lusitaniae. Tolerance results showed that C. lusitaniae YX3205 can tolerate up to 15% (v v-1 ) ethanol. In a solid-state simulated fermentation experiment, the content of 24 flavor substances was significantly increased in the fortified group, and the total ester content reached 4240.73 µg kg-1 , which was 2.8 times higher than that of the control group. CONCLUSION: The present study demonstrated the potential of C. lusitaniae YX3205 to enhance the flavor of baijiu, thereby serving as a valuable strain for the improvement of the flavor quality of baijiu. © 2024 Society of Chemical Industry.

The incidence, risk factors, management and prognosis of postoperative systemic complications after ophthalmic surgery: a retrospective study at a tertiary, academic referral hospital over a decade.

PURPOSE: To explore the incidence, risk factors, management and prognosis of systemic complications after ophthalmic surgeries. METHODS: A retrospective review of hospitalized patients undergoing ophthalmic surgeries between 2012 and 2022 at Peking Union Medical College Hospital was performed to summarize and analyse the postoperative systemic complications. Multivariate logistic and linear regression analyses were conducted to clarify the risk factors of postoperative systemic complications and factors associated with the severity of adverse events. RESULTS: A total of 34,841 patients underwent inpatient ophthalmic surgery, among which 162 systemic complications occurred in 150 patients during postoperative hospitalization. The overall incidence rate was 0.4%, with cardiovascular events (48.1%), digestive events (13.6%) and fever (12.3%) being the leading causes. About 17.3% of the cases had conditions improved after observation, 19.1% after symptomatic treatment, 54.9% had consultation with specific intervention and 8.6% were transferred to the corresponding departments for specialized treatment. For the prognosis, 93.8% had condition improved, 5.6% chose voluntary discharge without improvement, and one patient died of respiratory failure caused by postoperative pulmonary infection. The worse ADL (activities of daily living) grading, indication of primary intraocular lymphoma or intraocular tumour, surgery of simple pars plana vitrectomy (PPV), PPV with silicone oil tamponade, PPV with gas tamponade, general anaesthesia, history of diabetes mellitus (DM), chronic heart failure and digestive system disease were the risk factors positively correlated with postoperative systemic complications (p < .05). The worse ADL grading, history of DM and respiratory system disease were also positively correlated with the severity of the adverse events (p < .05). CONCLUSIONS: The incidence of postoperative systemic complications was low among patients undergoing ophthalmic surgery, most were mild and could be relieved after observation, symptomatic or specialist consultation. Patients with worse ADL and history of DM should be paid extra attention.

A novel myeloid cell marker genes related signature can indicate immune infiltration and predict prognosis of hepatocellular carcinoma: Integrated analysis of bulk and single-cell RNA sequencing.

Myeloid cells are physiologically related to innate immunity and inflammation. Tumor-associated myeloid cells gained increasing interest because of their critical roles in tumor progression and anticancer immune responses in human malignancies. However, the associations between tumor-associated myeloid cell-related genes and hepatocellular carcinoma have yet to be revealed. Here, through the integrating analysis of bulk and single-cell RNA (scRNA) sequencing of public HCC samples, we developed a gene signature to investigate the role of HCC-specific myeloid signature genes in HCC patients. We firstly defined 317 myeloid cell marker genes through analyzing scRNA data of HCC from the GEO dataset. After selecting the differentially expressed genes, eleven genes were also proved prognostic. Then we built a gene signature from the TCGA cohort and verified further with the ICGC dataset by applying the LASSO Cox method. An eight genes signature (FABP5, C15orf48, PABPC1, TUBA1B, AKR1C3, NQO1, AKR1B10, SPP1) was achieved finally. Patients in the high risk group correlated with higher tumor stages and poor survival than those in the low-risk group. The risk score was proved to be an independent risk factor for prognosis. The high risk group had higher infiltrations of dendritic cells, macrophages and Tregs. And the APC co-inhibition, T cell co-inhibition pathways were also activated. Besides, the risk score positively correlated with multidrug resistance proteins. In conclusion, our myeloid cell marker genes related signature can predict patients' survival and may also indicate the levels of immune infiltration and drug resistance.

Chromosome-level genome assembly and resequencing of camphor tree (Cinnamomum camphora) provides insight into phylogeny and diversification of terpenoid and triglyceride biosynthesis of Cinnamomum.

Cinnamomum species attract attentions owing to their scents, medicinal properties, and ambiguous relationship in the phylogenetic tree. Here, we report a high-quality genome assembly of Cinnamomum camphora, based on which two whole-genome duplication (WGD) events were detected in the C. camphora genome: one was shared with Magnoliales, and the other was unique to Lauraceae. Phylogenetic analyses illustrated that Lauraceae species formed a compact sister clade to the eudicots. We then performed whole-genome resequencing on 24 Cinnamomum species native to China, and the results showed that the topology of Cinnamomum species was not entirely consistent with morphological classification. The rise and molecular basis of chemodiversity in Cinnamomum were also fascinating issues. In this study, six chemotypes were classified and six main terpenoids were identified as major contributors of chemodiversity in C. camphora by the principal component analysis. Through in vitro assays and subcellular localization analyses, we identified two key terpene synthase (TPS) genes (CcTPS16 and CcTPS54), the products of which were characterized to catalyze the biosynthesis of two uppermost volatiles (i.e. 1,8-cineole and (iso)nerolidol), respectively, and meditate the generation of two chemotypes by transcriptional regulation and compartmentalization. Additionally, the pathway of medium-chain triglyceride (MCT) biosynthesis in Lauraceae was investigated for the first time. Synteny analysis suggested that the divergent synthesis of MCT and long-chain triglyceride (LCT) in Lauraceae kernels was probably controlled by specific medium-chain fatty acyl-ACP thioesterase (FatB), type-B lysophosphatidic acid acyltransferase (type-B LPAAT), and diacylglycerol acyltransferase 2b (DGAT 2b) isoforms during co-evolution with retentions or deletions in the genome.

Enalapril increases the urinary excretion of metformin in rats by inducing multidrug and toxin excretion protein 1 in the kidney.

Two-thirds of patients with type 2 diabetes mellitus have hypertension, and thus the combination of two or more drugs to treat these diseases is common. It has been shown that the combination of metformin and enalapril has beneficial effects, but few studies have evaluated the interactions between these two drugs. This study investigated the effects of enalapril on the pharmacokinetics and urinary excretion of metformin in rats, with a focus on transporter-mediated drug interactions. Rats were dosed orally with metformin alone (100 mg/kg) or in combination with enalapril (4 mg/kg). The concentration of metformin was measured by high performance liquid chromatography and the level of organic cation transporters (rOCTs) and multidrug and toxin excretion protein 1 (rMATE1), which mediate the uptake and efflux of metformin, respectively, were evaluated by immunoblotting. After single and 7-day dosing, the plasma concentration of metformin in the co-administration group was significantly lower than that in the metformin-only group, and the CL/F and urinary excretion were increased in the co-administration group. Enalapril did not affect the Kp of metformin but reduced renal slice-uptake of metformin. The expression of rMATE1 was increased, whereas rOCT2 expression was decreased in rat kidney. Importantly, long-term co-administration of metformin and enalapril markedly decreased the level of lactic acid and uric acid in the blood. Enalapril increases the urinary excretion of metformin through the up-regulation of rMATE1. This reveals a new mechanism of drug interactions and provides a basis for drug dosage adjustment when these drugs are co-administered.

Assessment of structural brain changes in patients with type 2 diabetes mellitus using the MRI-based brain atrophy and lesion index.

Patients with type 2 diabetes mellitus (T2DM) often have cognitive impairment and structural brain abnormalities. The magnetic resonance imaging (MRI)-based brain atrophy and lesion index can be used to evaluate common brain changes and their correlation with cognitive function, and can therefore also be used to reflect whole-brain structural changes related to T2DM. A total of 136 participants (64 men and 72 women, aged 55-86 years) were recruited for our study between January 2014 and December 2016. All participants underwent MRI and Mini-Mental State Examination assessment (including 42 healthy control, 38 T2DM without cognitive impairment, 26 with cognitive impairment but without T2DM, and 30 T2DM with cognitive impairment participants). The total and sub-category brain atrophy and lesion index scores in patients with T2DM with cognitive impairment were higher than those in healthy controls. Differences in the brain atrophy and lesion index of gray matter lesions and subcortical dilated perivascular spaces were found between non-T2DM patients with cognitive impairment and patients with T2DM and cognitive impairment. After adjusting for age, the brain atrophy and lesion index retained its capacity to identify patients with T2DM with cognitive impairment. These findings suggest that the brain atrophy and lesion index, based on T1-weighted and T2-weighted imaging, is of clinical value for identifying patients with T2DM and cognitive impairment. Gray matter lesions and subcortical dilated perivascular spaces may be potential diagnostic markers of T2DM that is complicated by cognitive impairment. This study was approved by the Medical Ethics Committee of University of South China (approval No. USC20131109003) on November 9, 2013, and was retrospectively registered with the Chinese Clinical Trial Registry (registration No. ChiCTR1900024150) on June 27, 2019.

In Situ Pyrolysis Tracking and Real-Time Phase Evolution: From a Binary Zinc Cluster to Supercapacitive Porous Carbon.

The in situ tracking of the pyrolysis of a binary molecular cluster [Zn7 (µ3 -CH3 O)6 (L)6 ][ZnLCl2 ]2 is presented with one brucite disk and two mononuclear fragments (L=mmimp: 2-methoxy-6-((methylimino)-methyl)phenolate) to porous carbon using TG-MS from 30 to 900 °C. Following up the spilled gas product during the decomposed reaction of zinc cluster along the temperature rising, and in conjunction with XRD, SEM, BET and other materials characterization, where three key steps were observed: 1) cleavage of the bulky external ligand; 2) reduction of ZnO and 3) volatilization of Zn. The real-time-dependent phase-sequential evolution of the remaining products and the processing of pore forming template transformation are proposed simultaneously. The porous carbon structure featuring a uniform nano-sized pore distribution synthesized at 900 °C with the highest surface area of 1644 m2 g-1 and pore volume of 0.926 cm3 g-1 exhibits the best known capacitance of 662 F g-1 at 0.5 A g-1 .

Knowledge Domain and Emerging Trends in Vinegar Research: A Bibliometric Review of the Literature from WoSCC.

Vinegar is one of the most widely used acidic condiments. In recent decades, rapid advances have been made in the area of vinegar research, and the intellectual structure pertaining to this domain has significantly evolved. Thus, it is important that scientists keep abreast of associated developments to ensure an appropriate understanding of this field. To facilitate this current study, a bibliometric analysis method was adopted to visualize the knowledge map of vinegar research based on literature data retrieved from the Web of Science Core Collection (WoSCC) database. In total, 883 original research and review articles from between 1998 and 2019 with 19,663 references were analyzed by CiteSpace. Both a macroscopical sketch and microscopical characterization of the whole knowledge domain were realized. According to the research contents, the main themes that underlie vinegar research can be divided into six categories, that is, microorganisms, substances, health functions, production technologies, adjuvant medicines, and vinegar residues. In addition to the latter analysis, emerging trends and future research foci were predicted. Finally, the evolutionary stage of vinegar research was discerned according to Shneider's four-stage theory. This review will help scientists to discern the dynamic evolution of vinegar research, as well as highlight areas for future research.

Enhancing expression level and stability of transgene mediated by episomal vector via buffering DNA methyltransferase in transfected CHO cells.

Nonviral episomal vectors present attractive alternative vehicles for gene therapy applications. Previously, we have established a new type of nonviral episomal vector-mediated by the characteristic motifs of matrix attachment regions (MARs), which is driven by the cytomegalovirus (CMV) promoter. However, the CMV promoter is intrinsically susceptible to silencing, resulting in declined productivity during long-term culture. In this study, Chinese hamster ovary (CHO) cells and DNA methyltransferase-deficient (Dnmt3a-deficient) CHO cells were transfected with plasmid-mediated by MAR, or CHO cells were treated with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine. Flow cytometry, plasmid rescue experiments, fluorescence in-situ hybridization (FISH), and bisulfite sequencing were performed to observe transgene expression, its state of existence, and the CpG methylation level of the CMV promoter. The results indicated that all DNA methylation inhibitor and methyltransferase deficient cells could increase transgene expression levels and stability in the presence or absence of selection pressure after a 60-generation culture. Plasmid rescue assay and FISH analysis showed that the vector still existed episomally after long-time culture. Moreover, a relatively lower CMV promoter methylation level was observed in Dnmt3a-deficient cell lines and CHO cells treated with 5-Aza-2'-deoxycytidine. In addition, Dnmt3a-deficient cells were superior to the DNA methylation inhibitor treatment regarding the transgene expression and long-term stability. Our study provides the first evidence that lower DNA methyltransferase can enhance expression level and stability of transgenes mediated by episomal vectors in transfected CHO cells.

Difference in the Formation of Two Structural Types of V-Shaped MII3 Clusters: Diffraction, Mass Spectrometry, and Magnetism.

A way to understand kinetics and explore mechanism of reactions is to identify the intermediates and their relative energetics. In this respect, low-energy electrospray ionization mass spectrometry is providing information on possible intermediates that can be tandemly verified using crystallography of the products. This has been extended to the study of the formation of functional clusters of transition metals under varying conditions. The reaction of NiL2 (L = 2-ethoxy-6-( N-methyliminomethyl)phenolate) with MII(H2O)6(ClO4)2 in the presence of Et3N base leads to [Ni xM7- x(µ3-OH)6L6]2+ according to NiL2 → [M2L3]+ → [M4(OH)2L4]2+ → [M7(OH)6L6]2+. In contrast, its reaction with MII(H2O)6(NO3)2 in the absence of base leads to two crystallographic structural types [MII3L4(NO3)2(H2O)2]·CH3CN for M = Ni (I-Ni3) or Co (I-Co xNi3- x, x = 0-3) and [MIINiII2L4(NO3)2] for M = Zn (II-ZnNi2) or Co (II-CoNi2). Interestingly, ESI-MS suggests three slightly different formation processes: for I-Ni3, {NiL2 → [Ni2L(NO3)2]+ → [Ni2L2(NO3)]+ → [Ni2L3]+ → [Ni3L4(NO3)]+}; for II-ZnNi2, {NiL2 → [ZnNiL2(NO3)]+ → [ZnNi2L4(NO3)]+}; for II-CoNi2 and I-Co xNi3- x, {NiL2 → [M2L2(NO3)]+ → [M2L3]+ → [M3L4(NO3)]+}. Magnetization measurements reveal the site of each metal ionin II-ZnNi2 and the number of single electrons within different clusters. Without the base, there is an interplay between the weak coordinating nitrate and water stabilizing the two structural types via the different formation processes. The results indicate that not only the strength of the ligand matters but also the ionic sizes and possibly softness of the metals may be implicated.

Allocating on coal consumption and CO2 emission from fair and efficient perspective: empirical analysis on provincial panel data of China.

This paper considers a problem of how to allocate resource effectively and equitably among provinces. To address the problem, a total factor resource input-oriented data envelopment analysis (DEA) model is used to evaluate the energy and environmental efficiency for 30 provinces in China during 2009-2013 in this paper. Based on the evaluation results, from efficient and fair perspective, a revised DEA-based resource allocation model is established. It is worth pointing out that the model takes the input orientation and output orientation into account at the same time and can be used to allocate coal consumption and carbon emission by 2020 for 30 provinces in China. Results indicate that if the Chinese government wants to fulfill the CO2 emission reduction targets of 40-45% by 2020, and coal consumption intensity reduction target during 13th Five-Year Plan, inefficient provinces will undertake more coal consumption and carbon emission intensity reduction obligation share. And provinces with historical high coal consumption and high CO2 emission intensity will have greater potential of coal consumption and carbon emission intensity reduction. In addition, this paper set several scenarios of gross domestic product (GDP) growth rate, under the scenarios analysis, finds the growth rate of GDP has negative effect on reduction of coal consumption and carbon dioxide emissions intensity. This research provides more realistic practical significance for achieving sustainable economic development.

Comprehensive evaluation on low-carbon development of coal enterprise groups.

Scientifically evaluating the level of low-carbon development in terms of theoretical and practical significance is extremely important to coal enterprise groups for implementing national energy-related systems. This assessment can assist in building institutional mechanisms that are conducive for the economic development of coal business cycle and energy conservation as well as promoting the healthy development of coal enterprises to realize coal scientific development and resource utilization. First, by adopting systematic analysis method, this study builds low-carbon development evaluation index system for coal enterprise groups. Second, to determine the weight serving as guideline and criteria of the index, analytic hierarchy process (AHP) is applied using integrated linear weighted sum method to evaluate the level of low-carbon development of coal enterprise groups. Evaluation is also performed by coal enterprise groups, and the process comprises field analysis and evaluation. Finally, industrial policies are proposed regarding the development of low-carbon coal conglomerate strategies and measures. This study aims mainly to guide the low-carbon development of coal enterprise groups, solve the problem of coal mining and the destruction of ecological environment, support the conservation of raw materials and various resources, and achieve the sustainable development of the coal industry.

Tuning Semiconductor Performance of Nickel Complexes through Crystal Transformation.

Crystal transformation between two polymorphs (green, 1-G, and red, 1-R) of the square-planar nickel complex NiL2 (L = 2-ethoxy-6-( N-methyliminomethyl)phenolate) and their tuning effect to semiconductor properties were studied both experimentally and theoretically. When 1-G is heated to 413 K, it converts to 1-R, whereas soaking 1-R in several kinds of solvents causes it to revert to 1-G. Crystallographic and PXRD studies reveal the dramatic changes in crystal dimensions due to the changes of packing models. Heating device made from 1-G (D-1-G(298)) at 413 K significantly increases the electrical conductivity from 6.55 × 10-4 S cm-1 for D-1-G(298) to 1.11 × 10-3 S cm-1 for D-1-G(413), showing significant crystal form dependence. Heat-treating D-1-G and D-1-R devices at different temperatures clearly reveals the reason for the conductivity tuning. Thus, the conductivity of NiL2-based devices could be well tuned through crystal transformation by heating or by soaking in solvent. Theoretical calculations clearly revealed the reason for such conductivity changes and also predicted that both polymorphs are good p-type semiconductors with hole mobilities of 1.63 × 10-2 (1-G) and 2.11 × 10-1 cm2 V-1 s-1 (1-R).

Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg-1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg-1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway.

Deubiquitylation of hepatitis B virus X protein (HBx) by ubiquitin-specific peptidase 15 (USP15) increases HBx stability and its transactivation activity.

Hepatitis B virus X protein (HBx) plays important roles in viral replication and the development of hepatocellular carcinoma. HBx is a rapid turnover protein and ubiquitin-proteasome pathway has been suggested to influence HBx stability as treatment with proteasome inhibitors increases the levels of HBx protein and causes accumulation of the polyubiquitinated forms of HBx. Deubiquitinases (DUBs) are known to act by removing ubiquitin moieties from proteins and thereby reverse their stability and/or activity. However, no information is available regarding the involvement of DUBs in regulation of ubiquitylation-dependent proteasomal degradation of HBx protein. This study identified the deubiquitylating enzyme USP15 as a critical regulator of HBx protein level. USP15 was found to directly interact with HBx via binding to the HBx region between amino acid residues 51 and 80. USP15 increased HBx protein levels in a dose-dependent manner and siRNA-mediated knockdown of endogenous USP15 reduced HBx protein levels. Increased HBx stability and steady-state level by USP15 were attributable to reduced HBx ubiquitination and proteasomal degradation. Importantly, the transcriptional transactivation function of HBx is enhanced by overexpression of USP15. These results suggest that USP15 plays an essential role in stabilizing HBx and subsequently affects the biological function of HBx.

[Effects of metoprolol or/and pravastatin on the pharmacokinetics of metformin in rats].

This study investigates the effects of metoprolol (METO) or/and pravastatin (PRAV) on the pharmacokinetics of metformin (METF) in rats. Twenty-eight male SD rats were divided into METF group, METF+METO group, METF+PRAV group and METF+METO+PRAV group. Blood samples were collected at 10, 20, 40, 60, 90, 120, 180, 240, 360, 480 and 600 min after oral administration of metformin, and concentration of metformin in plasma was determined by HPLC. Compared to the METF group, Cmax of metformin was significantly decreased (P < 0.01) and MRT0−t , t1/2 and V were significantly increased in the METF+METO group; t1/2 was significantly decreased in the METF+PRAV group; Cmax was significantly decreased and MRT0−t was significantly increased in the METF+METO+PRAV group. Compared to the METF+METO group, MRT0−t of metformin was significantly decreased in the METF+METO+PRAV group. Compared to the METF+PRAV group, Cmax of metformin was significantly decreased (P < 0.01), and MRT0−t , t1/2 and V were significantly increased in the METF+METO+PRAV group. There exist multiple drug interactions of metformin, metoprolol and pravastatin in rats.

Metoprolol decreases the plasma exposure of metformin via the induction of liver, kidney and muscle uptake in rats.

Drug interactions are one of the commonest causes of side effects, particularly in long-term therapy. The aim of the current study was to investigate the possible effects of metoprolol on the pharmacokinetics of metformin in rats and to clarify the mechanism of drug interaction. In this study, rats were treated with metformin alone or in combination with metoprolol. Plasma, urine and tissue concentrations of metformin were determined by HPLC. Western blotting and real-time qPCR were used to evaluate the expression of rOCTs and rMATE1. The results showed that, after single or 7-day repeated administration, the plasma concentrations of metformin in the co-administration group were significantly decreased compared with that in the metformin group. However, the parameter V/F of metformin in the co-administration group was markedly increased compared with that in the metformin group. The hepatic, renal and muscular Kp of metformin were markedly elevated after co-administration with metoprolol. Consistently, metformin uptake in rat kidney slices was significantly induced by metoprolol. In addition, multiple administrations of metoprolol significantly reduced the expression of rMATE1 in rat kidney as well as the urinary excretion of metformin. Importantly, after long-term administration, lactic acid and uric acid levels in the co-administration group were increased by 25% and 26%, respectively, compared with that in the metformin group. These results indicate that metoprolol can decrease the plasma concentration of metformin via the induction of hepatic, renal and muscular uptake, and long-term co-administration of metformin and metoprolol can cause elevated lactic acid and uric acid levels. Copyright © 2016 John Wiley & Sons, Ltd.

Low expression of ARID1A correlates with poor prognosis in intrahepatic cholangiocarcinoma.

AIM: To investigate the relationship between ARID1A expression and clinicopathologic parameters, as well as its prognostic value, for patients with intrahepatic cholangiocarcinoma (IHCC). METHODS: We assessed ARID1A protein and mRNA expression in IHCC tissues and paracarcinomatous (PC) tissues from 57 patients with IHCC using western blot and quantitative real-time reverse transcription polymerase chain reaction, respectively. We used Fisher's exact and χ(2) tests to analyze relationships between clinicopathological parameters and ARID1A expression. The Kaplan-Meier method and Cox regression were used to analyze survival. RESULTS: The mean ARID1A protein level in IHCC tissues was 1.16 ± 0.36 relative units (RU), which was significantly lower than that in PC tissues (1.26 ± 0.21 RU, P < 0.01) and NL tissues (1.11 ± 0.31, P < 0.001). The mean ARID1A mRNA level in IHCC tissues (1.20 ± 0.18) was also lower than that in PC tissues (1.27 ± 0.15, P < 0.001) and normal liver tissues (1.15 ± 0.34, P < 0.001). Low ARID1A expression was significantly associated with tumor nodules, vein invasion, and recurrence. Median overall survival (OS) and disease-free survival (DFS) for the low ARID1A expression group was 15.0 and 7.0 mo, respectively, which were significantly shorter than those for the high ARID1A expression group at 25.0 and 22.0 mo (OS: P < 0.01; DFS: P < 0.001), respectively. Low ARID1A expression was significantly associated with worse OS (HR = 3.967, 95%CI: 1.299-12.118, P = 0.016) in multivariate analyses. CONCLUSION: Low expression of ARID1A is associated with poor prognosis in patients with IHCC, and thus may be a potential prognostic biomarker candidate in IHCC.

Downregulation of KIF1B mRNA in hepatocellular carcinoma tissues correlates with poor prognosis.

AIM: To compare kinesin family member 1B (KIF1B) expression with clinicopathologic parameters and prognosis in hepatocellular carcinoma (HCC) patients. METHODS: KIF1B protein and mRNA expression was assessed in HCC and paracarcinomatous (PC) tissues from 68 patients with HCC using Western blot and quantitative real-time reverse transcription-PCR, respectively. Student's t-tests were used to analyze relationships between clinicopathologic parameters and KIF1B expression, the Kaplan-Meier method was used to analyze survival outcomes, and the log-rank test was used to compare survival differences between groups. RESULTS: Mean protein and mRNA levels of KIF1B were similar between HCC and PC tissues. However, HCC tissues with vein invasions had significantly lower KIF1B protein levels compared to those without vein invasions (2.30 ± 0.82 relative units vs 2.77 ± 0.84 relative units, P < 0.05). KIF1B protein levels in HCC tissues from patients with recurrence during the follow-up period were significantly lower than those without recurrence (2.31 ± 0.92 relative units vs 2.80 ± 0.80 relative units, P < 0.05). However, KIF1B protein and mRNA expression in HCC patients was not associated with other clinicopathologic parameters. Ratios of KIF1B mRNA expression in HCC tissues to those in PC tissues were correlated with overall survival (13.5 mo vs 20.0 mo, P < 0.05) and disease-free survival (11.5 mo vs 19.5 mo, P < 0.05). CONCLUSION: Downregulation of KIF1B in HCC tissues is associated with poor prognosis; additional clinical studies are needed to confirm whether KIF1B can serve as a prognostic marker.

Unprecedented metal-mediated in situ reactions of heterocyclic disulfide of di[4-(pyridin-2-yl)pyrimidinyl]disulfide.

By the combination of different metal salts and solvents, four unprecedented in situ reactions have been discovered for heterocyclic disulfide of 2-ppds (2-ppds = di[4-(pyridin-2-yl)pyrimidinyl]disulfide). In the CH3CN-DMF solvent, reaction of 2-ppds with AgNO3 produced a one-dimensional chain structure of {[Ag2(1L)2]·2CH3CN}n (1), wherein 2-ppds was converted into its sulfonate of 1L by means of oxidative cleavage of the S-S bond. In the CH3CN-DCM solvent, reaction between 2-ppds and Cu(ClO4)2 yielded a discrete mononuclear Cu(II) coordination structure of [Cu(2L)2H2O)](ClO4)2 (2), of which 2-ppds was turned into a totally unexpected zwitterion product of 2L via C-S bond scission followed by O substitution. In the MeOH-DCM solvent, reaction of 2-ppds with Co(ClO4)2 resulted in a mononuclear Co(III) coordination structure of [Co(3L)2]ClO4·2CH3OH·H2O (3), in which 2-ppds was transformed into its persulfide of 3L via selective single C-S bond rupture. In the CH3CN-DMF solvent, reaction between 2-ppds and CuI afforded a binuclear mixed-valence Cu(I)Cu(II) coordination structure of [Cu2I(4L)2] (4), wherein 2-ppds was converted into its thiolate of 4L through homolytic S-S bond cleavage. The reaction mechanisms of these reactions have also been discussed on the basis of these in situ generated coordination structures coupled with our previous observations on 2-ppds.