Analysis of latrine fecal odor release pattern and the deodorization with composited microbial agent.

As an important source of malodor, the odor gases emitted from public toilet significantly interfered the air quality of living surroundings, resulting in environmental problem which received little attention before. Thus, this paper explored the odor release pattern of latrine feces and deodorization effect with composited microbial agent in Chengdu, China. The odor release rules were investigated in sealed installations with a working volume of 9 L for 20 days. The odor units (OU), ammonia (NH3), hydrogen sulfide (H2S) and total volatile organic compounds (TVOC) were selected to assess the release of malodorous gases under different temperature and humidity, while the highest malodor release was observed under 45℃, with OU and TVOC concentration was 643.91 ± 2.49 and 7767.33 ± 33.50 mg/m3, respectively. Microbes with deodorization ability were screened and mixed into an agent, which composited of Bacillus amyloliquefaciens, Lactobacillus plantarum, Enterococcus faecalis and Pichia fermentans. The addition of microbial deodorant could significantly suppress the release of malodor gas during a 20-day trial, and the removal efficiency of NH3, H2S, TVOC and OU was 81.50 %, 38.31 %, 64.38 %, and 76.86 %, respectively. The analysis of microbial community structure showed that temperature was the main environmental factor driving the microbial variations in latrine feces, while Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes were the main bacteria phyla involved in the formation and emission of malodorous gases. However, after adding the deodorant, the abundance of Bacteroidetes, Proteobacteria and Actinobacteria were decreased, while the abundance of Firmicutes was increased. Furthermore, P. fermentans successfully colonized in fecal substrates and became the dominant fungus after deodorization. These results expanded the understanding of the odor release from latrine feces, and the composited microbial deodorant provided a valuable basis to the management of odor pollution.

A time-course transcriptome analysis revealing the potential molecular mechanism of early gonadal differentiation in the Chinese giant salamander.

The Chinese giant salamander (CGS) Andrias davidianus is the largest extant amphibian and has recently become an important species for aquaculture with high economic value. Meanwhile, its wild populations and diversity are in urgent need of protection. Exploring the mechanism of its early gonadal differentiation will contribute to the development of CGS aquaculture and the recovery of its wild population. In this study, transcriptomic and phenotypic research was conducted on the critical time points of early gonadal differentiation of CGS. The results indicate that around 210 days post-hatching (dph) is the critical window for female CGS's gonadal differentiation, while 270 dph is that of male CGS. Besides, the TRPM1 gene may be the crucial gene among many candidates determining the sex of CGS. More importantly, in our study, key genes involved in CGS's gonadal differentiation and development are identified and their potential pathways and regulatory models at early stage are outlined. This is an initial exploration of the molecular mechanisms of CGS's early gonadal differentiation at multiple time points, providing essential theoretical foundations for its captive breeding and offering unique insights into the conservation of genetic diversity in wild populations from the perspective of sex development.

Risk factors of diffuse alveolar hemorrhage in Chinese patients with systemic lupus erythematosus.

This study aimed to investigate the frequency and features of diffuse alveolar hemorrhage (DAH) in Chinese patients with systemic lupus erythematosus (SLE) and evaluate the association of DAH with the features. A total of 943 patients with SLE were categorized into two groups: 896 patients without DAH and 47 patients with DAH. The demographic data, clinical and laboratory findings, and SLE disease activity index 2000 of all patients were statistically analyzed. The DAH frequency in patients with SLE was 4.98%, and the mortality rate of DAH was 42.55%. The clinical features with statistical differences between the two groups were analyzed by multivariate logistic regression, and the results suggested that shorter disease duration [odds ratio (OR): 0.972, 95% confidence interval (CI) 0.946, 0.998], younger age (OR: 0.867, 95% CI 0.764, 0.984), moderate (OR: 25.949, 95% CI 3.316, 203.065) or severe (OR: 24.904, 95% CI 2.675, 231.859) anemia, abnormally elevated levels of urine protein (OR: 10.839, 95% CI 1.351, 86.938) and serum creatinine (OR: 14.534, 95% CI 5.012, 42.142), interstitial lung disease (OR: 6.569, 95% CI 2.053, 21.021), and infection (OR: 8.890, 95% CI 3.580, 22.077) were independent risk factors for the occurrence of DAH in patients with SLE. Moderate or severe anemia was highly suggestive of DAH.

The role of walnut bZIP genes in explant browning.

BACKGROUND: Basic leucine zipper (bZIP) proteins are important transcription factors in plants. To study the role of bZIP transcription factors in walnut explant browning, this study used bioinformatics software to analyze walnut bZIP gene family members, along with their transcript levels in different walnut tissues, to evaluate the transcriptional expression of this gene family during the primary culture of walnut explants and to reveal the mechanism of action of walnut bZIP genes in walnut explant browning. RESULTS: The results identified 65 JrbZIP genes in the walnut genome, which were divided into 8 subfamilies and distributed on 16 chromosomes. The results of transcriptome data analysis showed that there were significant differences in the expression of four genes, namely, JrbZIP55, JrbZIP70, JrbZIP72, and JrbZIP88, under both vermiculite and agar culture conditions. There were multiple hormone (salicylic acid, abscisic acid, auxin, and gibberellin) signaling and regulatory elements that are responsive to stress (low temperature, stress, and defense) located in the promoter regions of JrbZIP55, JrbZIP70, JrbZIP72, and JrbZIP88. The walnut JrbZIP55 protein and Arabidopsis bZIP42 protein are highly homologous, and the proteins interacting with Arabidopsis bZIP42 include the AT2G19940 oxidoreductases, which act on aldehyde or oxygen-containing donors. CONCLUSION: It is speculated that JrbZIP55 may participate in the regulation of browning in walnut explants.

Genome-Wide Identification and Analysis of the MADS-Box Transcription Factor Genes in Blueberry (Vaccinium spp.) and Their Expression Pattern during Fruit Ripening.

MADS-box is a class of transcriptional regulators that are ubiquitous in plants and plays important roles in the process of plant growth and development. Identification and analysis of blueberry MADS-box genes can lay a foundation for their function investigations. In the present study, 249 putative MADS-box genes were identified in the blueberry genome. Those MADS-box genes were distributed on 47 out of 48 chromosomes. The phylogenetic and evolutionary analyses showed that blueberry MADS-box genes were divided into 131 type I members and 118 type II members. The type I genes contained an average of 1.89 exons and the type II genes contained an average of 7.83 exons. Motif analysis identified 15 conserved motifs, of which 4 were related to the MADS domain and 3 were related to the K-box domain. A variety of cis-acting elements were found in the promoter region of the blueberry MADS-box gene, indicating that the MADS-box gene responded to various hormones and environmental alterations. A total of 243 collinear gene pairs were identified, most of which had a Ka/Ks value of less than 1. Nine genes belonging to SEP, AP3/PI, and AGL6 subfamilies were screened based on transcriptomic data. The expression patterns of those nine genes were also verified using quantitative PCR, suggesting that VcMADS6, VcMADS35, VcMADS44, VcMADS58, VcMADS125, VcMADS188, and VcMADS212 had potential functions in blueberry fruit ripening. The results of this study provide references for an in-depth understanding of the biological function of the blueberry MADS-box genes and the mechanism of blueberry fruit ripening.

Identification of risk and prognostic factors for intrahepatic vascular invasion in patients with hepatocellular carcinoma: a population-based study.

Background: The aim of this study was to develop nomograms to predict the risk of intrahepatic vascular invasion (IVI) of hepatocellular carcinoma (HCC) patients and estimate the overall survival (OS) and cancer-specific survival (CSS) of HCC patients with IVI. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with HCC from 2010 to 2015. Ultimately, 1,287 HCC patients with IVI were included in this study and randomly divided into training (n=901) and validation (n=386) cohorts. Multivariate logistic regression analysis and multivariate Cox proportional hazards regression analysis were performed to construct nomograms to visually quantify the risk of IVI in patients with HCC and predict the prognosis. The prediction effect of nomograms was evaluated using Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA), respectively. Results: The C-index of the nomogram for risk prediction was 0.730. The C-indices based on the nomogram were 0.762 [95% confidence interval (CI): 0.745-0.779] and 0.770 (95% CI: 0.753-0.787) for OS and CSS prediction in the training cohort, respectively. In the validation cohort, the C-indices were 0.779 (95% CI: 0.752-0.806) and 0.795 (95% CI: 0.768-0.822) for OS prediction and CSS prediction, respectively. Overall, the ROC curve, calibration plots, and DCA indicated the good performance of nomograms. Conclusions: We identified the relevant risk and prognostic factors for IVI in patients with HCC. The nomograms performed well on validation and may help to facilitate clinical decision-making.

Accounting for the importance of psychological distance in assessing public preferences for air quality improvement policies: an application of the integrated choice and latent variable model.

Assessing public preferences for air pollution control is essential to achieving effective air quality improvement, but the internal psychological factors affecting public preferences, especially psychological distance (PD), have only received limited attention. Therefore, this paper explores the role of PD in assessing public preferences for air quality improvement policies. Compared with previous studies that consider psychological factors in the choice model, this study incorporates PD into the choice model as a latent variable by considering both individual responses to measurement questions and socio-economic characteristics in the integrated choice and latent variable model. The results of this study clearly show that PD significantly affects public preferences for air quality improvement policies. Respondents with close PD had obvious preferences for air quality improvement, while those with distant PD were satisfied with the current situation and reluctant to improve it. After considering PD in the analysis, respondents' willingness to pay for one-unit level change of attributes "heavily polluted days," "good air days," "mortality," and "policy postponement" were respectively 10.3791CNY, 10.9005CNY, 11.0427CNY, 28.3412CNY per year. In addition, the paper also found men and respondents with lower levels of education and higher monthly incomes tended to view air pollution as psychologically distant and thus less willing to improve air quality. It is suggested that policy makers should reduce the PD of air pollution among these people by increasing publicity about the hazards of air pollution. This study not only contributes to the literature on the importance of PD in assessing individual preferences, but also provides constructive guidance for policy makers to assess the public's acceptability of air quality improvement.

Will information interventions affect public preferences and willingness to pay for air quality improvement? An empirical study based on deliberative choice experiment.

Environmental information is a prerequisite for public participation in air quality improvement, and the choice of such participation behavior is influenced by the intervention of environmental information. Nonetheless, there has been insufficient analysis of how information interventions affect public preferences and willingness to pay for air quality improvement. The combination of deliberative and choice experiment is used to explore the importance of information interventions for public participation in air quality improvement, and the changes in public preferences and willingness to pay for air quality improvement before and after information interventions are compared to analyze the impact of information interventions on evaluation results of air quality value. The results suggest that information interventions do alter the preferences and willingness of the public to pay for air quality improvement, significantly increasing the choice certainty of respondents and decreasing the protest response. In addition, women and high-income groups showed a stronger willingness to improve air quality after the information interventions, with 35.15 CNY, 44.07 CNY and 46.75 CNY increases in willingness to pay for improved urban green coverage rate, fewer haze days and reduced morbidity. The combination of deliberative information interventions and choice experiment will help improve the effectiveness of air quality value evaluation, stimulate public environmental awareness and willingness to participate, and the results will aid government environmental management.

Ecotourism and sustainable development: a scientometric review of global research trends.

With the increasing attention and awareness of the ecological environment, ecotourism is becoming ever more popular, but it still brings problems and challenges to the sustainable development of the environment. To solve such challenges, it is necessary to review literature in the field of ecotourism and determine the key research issues and future research directions. This paper uses scientometrics implemented by CiteSpace to conduct an in-depth systematic review of research and development in the field of ecotourism. Two bibliographic datasets were obtained from the Web of Science, including a core dataset and an expanded dataset, containing articles published between 2003 and 2021. Our research shows that ecotourism has been developing rapidly in recent years. The research field of ecotourism spans many disciplines and is a comprehensive interdisciplinary subject. According to the research results, the evolution of ecotourism can be roughly divided into three phases: human disturbance, ecosystem services and sustainable development. It could be concluded that it has entered the third stage of Shneider's four-stage theory of scientific discipline. The research not only identifies the main clusters and their advance in ecotourism research based on high impact citations and research frontier formed by citations, but also presents readers with new insights through intuitive visual images. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02190-0.

Steroid treatment response combined with serological mark in differentiating type-1 autoimmune pancreatitis from pancreatic cancer.

Autoimmune pancreatitis (AIP) and pancreatic cancer (PC) are two different diseases. Their diagnosis, treatment, and prognosis are different, and it is difficult to differentiate them. This study aimed to explore the role of steroid treatment response combined with serological mark in distinguishing type-1 AIP from PC. Clinical data were collected and compared from 50 cases of AIP (group 1) and 100 cases of PC (group 2). The diagnostic value of serum IgG4, CA19-9, globulin, and eosinophil cell (EC) were evaluated. The response of steroid treatment of 28 patients with atypical imaging in group 1 was analyzed. After 2 weeks, the patients were classified as positive and negative steroid response according to the manifestations and/or the radiological changes. The positive response cases (n = 20) were confirmed as AIP, whereas negative ones (n = 8) were finally diagnosed as PC after complete resection. Serum globulin, IgG4, and EC levels in group 1 were significantly higher than those in group 2 (P < .01), and CA19-9 levels were distinctly lower in group 1 (P < .01). The level of serum IgG4 was related to the accuracy of diagnosis of AIP on the basis of the result of logistic regression analysis. Two-weeks steroid therapy response combined with serum IgG4 levels contribute to the differential diagnosis AIP and PC. However, regular and long-term follow-up were important for the differential diagnosis. There was an urgent need to explore the specific markers that distinguish these 2 entities.

TOP2A inhibition reverses drug resistance of hepatocellular carcinoma to regorafenib.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death attributed to high frequency of metastasis and multiple drug resistance. We aim to examine the underlying molecular mechanism and to seek potential strategies to reverse primary/acquired resistance to regorafenib. Topoisomerase IIα (TOP2A) is critical for tumorigenesis and carcinogenesis. Clinically, high-TOP2A expression was correlated to shorter overall survival (OS) of patients, but its role in drug resistance of HCC remains unknown. Here, we screened the expression profiling of TOP2A in HCC and identified TOP2A as an upregulated gene involved in the resistance to regorafenib. Sustained exposure of HCC cells to regorafenib could upregulate the expression of TOP2A. Silencing TOP2A enhanced HCC cells' sensitivity to regorafenib. TOP2A inhibition by doxorubicin or epirubicin synergized with regorafenib to suppress the growth of sorafenib-resistant HCC tumors that possessed the sorafenib-resistant features both in vitro and in vivo. Thus, targeting TOP2A may be a promising therapeutic strategy to alleviate resistance to regorafenib and thus improving the efficacy of HCC treatment.

[Fostering the chemistry and biology dual-disciplinary core literacy].

Improving students' comprehensive quality and developing their core literacy are the training objectives of high school subject curriculums, which puts forward new requirements for teachers' professionalism and core literacy. In order to adapt to the high school curriculum reform and the new college entrance examination reform, the Ministry of Education approved the development of high-quality, integrated and master-level high school teachers training pilot program. The aim of this program was to foster a group of dual-disciplinary integrated high school teachers who are suitable for teaching, enjoying teaching and skillful in teaching. How to foster the dual-disciplinary core literacy of normal students through subject curriculum is one of the challenges faced by the pilot program. Following the training objectives of the pilot program "Chemistry and Biological Sciences", we proposed to integrate the dual-disciplinary literacy into four aspects: material concept, scientific thinking, inquiry practice, attitude and responsibility. This was proposed based on analyzing the core literacy of the disciplines of chemistry and biology, and aimed to promote teachers and normal students' understanding and practice of dual-discipline core literacy. With biochemistry course as an example, we further explored and practiced on how to foster the dual-disciplinary core literacy of normal students, aiming to provide reference for the reform of other courses included in the dual-disciplinary integrated programs.

Can respondent uncertainty be ignored when exploring heterogeneity in public preferences for air pollution treatment policies? Comparative results from choice experiment analysis.

Based on choice experiment (CE), evaluating the public's heterogeneous preferences and willingness to pay (WTP) for air pollution treatment policies can provide useful social views for the reasonable formulation of treatment schemes. However, the application of CE contains an implicit assumption that respondents understand their real preferences and can make choices with complete certainty. In reality, for a variety of reasons, not all respondents are absolutely certain about their responses, this assumption distinctly is hard to be consistent with reality. To explore the impact of respondent uncertainty on the public's WTP and heterogeneous preferences for air pollution treatment policies, this study introduces the critical point and exponential weighting methods to deal with this uncertainty in the context of CE and conducts comparative analysis based on the random parameters logit (RPL) and latent classes models (LCM). The results show that, ignoring uncertainty leads to distortions in the public's WTP and preference characteristics. In the RPL models, on average, the WTP for attributes is overstated by 32.10%. Our results also reveal that, whether to consider uncertainty does not affect the ranking of the implicit prices of these attributes. After incorporating uncertainty into the analysis, respondents were divided into two potential groups with different preferences, namely the environment-focused group (79.44%) and the price-focused group (20.56%), which is quite distinct from research results of ignoring the uncertainty. Contribution of this study is not only to provide theoretical insights for exploring the effects of uncertainty on public preferences based on CE, but also to provide valuable guidance for policy makers to formulate more accurate and effective treatment measures.

Improvement of sewage sludge anaerobic digestion through synergistic effect combined trace elements enhancer with enzyme pretreatment and microbial community response.

In this study, a double E strategy (enzymes and enhancer) characterized by high efficiency for enhancing sewage sludge anaerobic digestion (AD) is proposed. This strategy combines addition of trace elements (TEs) enhancer and enzyme pretreatment, inducing a synergistic effect on AD, and it is more effective and economical compared with TEs addition or enzyme pretreatment in isolation. When adding 400 U/g cocktail enzymes and 1.24% trance elements enhancers, the cumulative methane production and the maximum daily methane increased yield by 45.29% and 84.7%, respectively. According to microbial community analysis, the double E strategy significantly motivate the growth of acetogens and protein fermenting bacterium. The relative abundance of Fermentimonas and Lutispora increased by 6.15% and 5.4%, respectively. Archaeal community analysis and changes in the mcrA gene abundance demonstrate enrichment of hydrogenotrophic methanogens, with the methanogens exhibiting high vitalities and stress resistance. The double E strategy could be a promising way to improve industrial sewage sludge AD efficiency.

Analyses of deodorization performance of mixotrophic biotrickling filter reactor using different industrial and agricultural wastes as packing material.

In this study, to efficiently remove malodorous gas and reduce secondary pollution under mixotrophic conditions, pine bark, coal cinder, straw and mobile bed biofilm reactor (MBBR) fillers were used as packing materials in a biological trickling filter (BTF) to simultaneously treat high-concentration H2S and NH3. The results showed that the removal rate of BTF-A filled with pine bark was the highest, which was 86.31% and 94.06% under the H2S and NH3 loading rates of 53.59 g/m³·h while the empty bed residence time (EBRT) was 40.5 s. The theoretical maximum load was obtained by fitting the kinetic curve, and the value were 90.09 g H2S m-³·h-1 and 172.41 g NH3 m-³·h-1. Meanwhile, after treating with 720 ppm of NH3, the average concentration of NO3- in the BTF circulating fluid was only 127.58 mg/L, indicating the better performance of secondary pollutants control. Microbiological analysis showed that Dokdonella, Micropruina, Candidatus_Alysiosphaera, Nakamurella and Thiobacillus possessed high abundance at the genus level, and their entire percentage in four BTF reactors were 62.87%, 46.32%, 47.98%, and 57.35% respectively. It is worthwhile that the genera Comamonas and Trichococcus with heterotrophic nitrification and aerobic denitrification capabilities and proportion of 3.66%, 1.45%, 5.43%, and 3.23% were observed in four reactors.

Poly-γ-glutamic acid production by simultaneous saccharification and fermentation using corn straw and its fertilizer synergistic effect evaluation.

Agricultural wastes rich in lignocellulosic biomass have been used in the production of poly-γ-glutamic acid (γ-PGA) through separate hydrolysis and fermentation (SHF), but this process is complicated and generates a lot of wastes. In order to find a simpler and greener way to produce γ-PGA using agricultural wastes, this study attempted to establish simultaneous saccharification and fermentation (SSF) with citric acid-pretreated corn straw. The possibility of Bacillus amyloliquefaciens JX-6 using corn straw as substrate to synthesize γ-PGA was validated, and the results showed that increasing the proportion of glucose in the substrate could improve the γ-PGA yield. Based on these preliminary results, the corn straw was pretreated using citric acid. Then, the liquid fraction (xylan-rich) was used for cultivation of seed culture, and the solid fraction (glucan-rich) was used as the substrate for SSF. In a 10-L fermenter, the maximum cumulative γ-PGA concentration in batch and fed-batch SSF were 5.08 ± 0.78 g/L and 10.78 ± 0.32 g/L, respectively. Moreover, the product from SSF without γ-PGA extraction was used as a fertilizer synergist, increasing the yield of pepper by 13.46% (P < 0.05). Our study greatly simplified the production steps of γ-PGA, and each step achieved zero emission as far as possible. The SSF process for γ-PGA production provided a simple and green way for lignocellulose biorefinery and sustainable cultivation in agriculture.

Co-occurrence of Wilson's disease and systemic lupus erythematosus: a case report and literature review.

BACKGROUND: Wilson's disease (WD) is a rare autosomal recessive disease associated with defective biliary excretion of copper. The simultaneous occurrence of WD and systemic lupus erythematosus (SLE) has seldom been reported. Therefore, this study aimed to report the co-occurrence of SLE and WD with hepatic involvement in a patient so as to improve the understanding of the coexistence of these two conditions. CASE PRESENTATION: A 35-year-old woman with SLE was found to have liver fibrosis during a routinely abdominal ultrasound examination. Her laboratory evaluation showed low serum ceruloplasmin and high 24 h urine copper levels. The slit-lamp examination revealed the presence of Kayseri-Fleischer ring in her cornea. Liver biopsy demonstrated the enlargement of the portal area with hyperplasia of the fibrous tissue, infiltration of lymphoid plasma cells, swelling of hepatocytes, and steatosis, demonstrating liver fibrosis. Ensuing genetic testing confirmed the diagnosis of WD. CONCLUSIONS: Clinicians should bear in mind that unexplained liver fibrosis in patients with SLE may be related to WD, so as to avoid a missed or delayed diagnosis.

Detection of anti-kelch-like 12 and anti-hexokinase 1 antibodies in primary biliary cholangitis patients in China.

OBJECTIVES: primary biliary cholangitis (PBC) is a chronic cholestatic disease, characterized by positive anti-mitochondrial autoantibodies (AMA) in 90-95 % patients. Anti-kelch-like 12 (anti-KLHL12) and anti-hexokinase1 (anti-HK1) antibodies have been identified as the two new serum markers in recent years, which are used in the diagnosis of AMA-negative PBC patients. The objective of the study was to examine the performance of these two new biomarkers in China. METHODS: a total of 192 patients were enrolled and screened for anti-KLHL12 and anti-HK1 antibodies and AMA by ELISA. Receiver operating characteristic (ROC curve) analysis was applied to examine the diagnostic importance of AMA, anti-KLHL12 and anti-HK1 antibodies. Furthermore, correlation analysis between some important biochemical indexes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], bilirubin, gamma-glutamil transferasa [γ-GT]), staging of pathological changes of the liver and the expression of novel antibodies in PBC patients were also examined. RESULTS: the positivity of the anti-HK1 antibody in AMA-positive PBC patients and AMA-negative patients was 44.7 % and 33.3 %, respectively. The specificity, proportion of positive patients (PPV) and proportion of negative patients (NPV) were 93 %, 89 % and 53 %, respectively. In contrast, the positivity to the anti-KLHL12 antibody in AMA-positive and negative PBC patients was 41.2 % and 22.2 %, respectively. Specificity, PPV and NPV were 98 %, 95 % and 52 %, respectively. The area under the curve (AUC) with anti-HK1 and anti-KLHL12 antibodies were 0.720 and 0.703. With the combination with anti-HK1 and anti-KLHL12 antibodies, the AUC of AMA increased from 0.889 to 0.891, increasing the sensitivity from 0.764 to 0.836. Anti-KLHL12 and anti-HK1-positive patients had higher serum levels of ALP, γ-GT and bilirubin, with statistically significant differences (p < 0.01) compared with anti-KLHL12 or anti-HK1-negative patients. Notably, correlation analysis showed a significant positive correlation between antibody expression and ALP, γ-GT and bilirubin serum levels (r = 0.735, 0.491, 0.466; p < 0.01). CONCLUSIONS: anti-HK1 and anti-KLHL12 antibodies have been identified as two significant biomarkers in PBC patients. Furthermore, the presence of these antibodies is likely to correlate with the severity of PBC.

Silencing KIF14 reverses acquired resistance to sorafenib in hepatocellular carcinoma.

For nearly a decade, sorafenib has served as a first-line chemotherapeutic drug for the treatment of hepatocellular carcinoma (HCC), but it displays only limited efficacy against advanced drug-resistant HCC. Regorafenib, the first second-line drug approved for treatment after sorafenib failure, can reverse resistance to sorafenib. We used bioinformatics methods to identify genes whose expression was differentially induced by sorafenib and regorafenib in HCC. We identified KIF14 as an oncogene involved in the acquired resistance to sorafenib in HCC and investigated its potential as a target for reversing this resistance. Sustained exposure of resistant HCC cells to sorafenib activated the AKT pathway, which in turn upregulated KIF14 expression by increasing expression of the transcription factor ETS1. Silencing KIF14 reversed the acquired resistance to sorafenib by inhibiting AKT activation and downregulating ETS1 expression by blocking the AKT-ETS1-KIF14 positive feedback loop. Moreover, injection of siKIF14 with sorafenib suppressed growth of sorafenib-resistant HCC tumors in mice. These results demonstrate that targeting KIF14 could be an effective means of reversing sorafenib failure or strengthening sorafenib's antitumor effects.

Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on T Cell Differentiation in Primary Biliary Cholangitis.

Exposure to dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is reported to affect the autoimmune system and increase the risk of autoimmune disease. Generally, dioxin exerts its toxicity via aryl hydrocarbon receptor (AhR). Primary biliary cholangitis (PBC) is a chronic autoimmune disease, and its pathogenesis involves the interplay between immune and environmental factors. This study showed the effect of dendritic cells (DCs) activated by TCDD on naïve CD4+ T cell differentiation in patients with PBC. CD14+ mononuclear cells were isolated from peripheral blood mononuclear cells (PBMCs) of patients with PBC and healthy people by magnetic cell separation and introduced into DCs. Two days after stimulation by TCDD, DCs were cocultured with naïve CD4+ T cells in a ratio of 1 : 2 for 3 days. Then, differentiation-related factors for naïve CD4+ T cells were detected by real-time fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and flow cytometry. The results showed that TCDD-activated DCs could promote Th1 and Th17 differentiation in patients with PBC. Therefore, this study demonstrated TCDD as an AhR agonist in regulating naïve CD4+ T cell differentiation in patients with PBC.