Effects of entecavir and tenofovir disoproxil fumarate on the incidence and severity of COVID-19 in patients with chronic hepatitis B.

BACKGROUND: Whether different anti-hepatitis B virus (HBV) drugs have different effects on COVID-19 is controversial. We aimed to evaluate the incidence of COVID-19 in chronic hepatitis B (CHB) patients receiving anti-HBV treatment, and to compare the impact of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on the severity of COVID-19. METHODS: CHB outpatients were enrolled from December 2022 to February 2023. Questionnaires were used to collect whether subjects were currently or previously had COVID-19 within the past 2 months, and the information of symptoms, duration, and severity if infected. RESULTS: Six hundred thirty CHB patients were enrolled, 64.3% (405/630) patients were currently or previously had COVID-19. No COVID-19 patient required hospitalization, intensive care unit admission, oxygen support or died. Majority of patients reported mild (32.8% [133/405]) and moderate (48.1% [195/405]) symptoms. After propensity score matching, 400 matched patients were obtained (ETV: 238; TDF: 162), among which the incidences of COVID-19 were comparable between ETV and TDF-treated patients (60.1% [143/238] vs. 64.2% [104/162], p = 0.468). The proportion of patients complicated with any symptom caused by COVID-19 were also similar (ETV vs. TDF: 90.9% [130/143] vs. 91.3% [95/104], p = 1.000). In addition, the severity of overall symptom was comparable between ETV and TDF-treated patients, in terms of proportion of patients complicated with severe symptom (9.8% vs. 8.7%, p = 0.989), symptom duration (4.3 vs. 4.3 days, p = 0.927), and symptom severity score (4.1 vs. 4.0, p = 0.758). Subgroup analysis supported these results. CONCLUSIONS: During the current pandemic, the vast majority of CHB patients experienced non-severe COVID-19, and ETV and TDF did not affect COVID-19 severity differently.

Estrogen-related receptor γ regulates hepatic triglyceride metabolism through phospholipase A2 G12B.

Hypersecretion of hepatic very LDL (VLDL)-associated triglyceride (TG) is the hallmark of hypertriglyceridemia. The estrogen-related receptor γ (ERRγ), an orphan nuclear receptor, plays crucial roles in the regulation of metabolic homeostasis, including TG formation in the liver. It remains unclear whether ERRγ regulates hepatic VLDL-TG secretion. We demonstrated that knockdown of ERRγ impairs hepatic VLDL-TG secretion in mice, whereas overexpression of ERRγ favors the secretion, indicating a novel role of ERRγ in hepatic TG metabolism. We found that ERRγ transcriptionally regulates the expression of PLA2G12B by binding to the promoter region of the Pla2g12b gene. In Pla2g12b-null mice, ERRγ fails to regulate hepatic VLDL-TG secretion. There is an apparent accumulation of large lipid droplets in the liver of Pla2g12b-null mice. These data suggest that ERRγ is a novel regulator of hepatic VLDL-TG secretion, which is mediated through the action on PLA2G12B.-Chen, L., Wu, M., Zhang, S., Tan, W., Guan, M., Feng, L., Chen, C., Tao, J., Chen, L., Qu, L. Estrogen-related receptor γ regulates hepatic triglyceride metabolism through phospholipase A2 G12B.

Bisphenol A differentially activates protein kinase C isoforms in murine placental tissue.

Bisphenol A is utilized to make polycarbonate plastics and is an environmental pollutant. Recent research has indicated that it is an endocrine disruptor and may interfere with reproductive processes. Our lab has previously shown that bisphenol A could regulate corticotrophin releasing hormone and aromatase in cultured placental cells. In the present study, the effect of bisphenol A on these two genes in the placenta was investigated in mice. Pregnant ICR mice were gavaged with bisphenol A at 2, 20 and 200mg/kg body weight/day from E13 to E16 and were euthanized at E17. Compared to the control mice, increased plasma estrogen and corticotrophin releasing hormone were observed in bisphenol A-treated mice. Messenger RNA quantification indicated that placental crh but not cyp19 was induced in mice treated with bisphenol A. Tracking the related signaling pathway, we found that protein kinase C ζ/λ and δ were activated in the placentas of bisphenol A-treated mice. As the gene promoter of crh contains CRE and the half site of ERE, either phospho-PKC or estrogen could stimulate the gene transactivation. These results indicate that bisphenol A might increase plasma concentrations of estradiol, testosterone, corticotrophin releasing hormone and placental phospho-PKC ζ/λ and δ in mice. Ultimately, the incidence of premature birth in these mice could increase.

Antibody response and safety of inactivated SARS-CoV-2 vaccines in chronic hepatitis B patients with and without cirrhosis.

Background: The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis. Patients and methods: A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7 days after the second dose were obtained using a questionnaire. Results: A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60 ng/ml, p = 0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week 4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week 2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16 weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6 months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p = 0.005; 2.73 vs. 2.41 ng/ml, p < 0.001). Conclusion: Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.

Hepatocyte nuclear factor-4 alpha regulates liver triglyceride metabolism in part through secreted phospholipase A2 GXIIB.

UNLABELLED: Hepatocyte nuclear factor-4 alpha (HNF-4α) is an important transcription factor governing the expression of genes involved in multiple metabolic pathways. Secreted phospholipase A(2) GXIIB (PLA(2) GXIIB) is an atypical member of a class of secreted phospholipases A(2) . We establish in this study that PLA(2) GXIIB is an HNF-4α target gene. We demonstrate that HNF-4α binds to a response element on the PLA(2) GXIIB promoter. Moreover, HNF-4α agonists induce PLA(2) GXIIB expression in human hepatocarcinoma cells. Importantly, PLA(2) GXIIB-null mice accumulate triglyceride, cholesterol, and fatty acids in the liver and develop severe hepatosteatosis resembling some of the phenotypes of liver-specific HNF-4α-null mice. These defects are in part due to compromised hepatic very low-density lipoprotein secretion. Finally, adenovirus-mediated overexpression of HNF-4α elevates serum triglyceride level in wild-type but not PLA(2) GXIIB-null mice. CONCLUSION: Collectively, these evidences suggest that HNF-4α is a key physiological PLA(2) GXIIB transcriptional regulator and that PLA(2) GXIIB is a novel mediator of triglyceride metabolism in the liver.

Mitigation of soil salinization and alkalization by bacterium-induced inhibition of evaporation and salt crystallization.

Soil salinization and alkalization is one of the most devastating environmental problems, threatening the sustainable development of agriculture. Bio-amelioration using microorganisms such as bacteria is a promising method for the remediation of calcareous sodic and saline-sodic soil due to its high efficiency, low cost and environmental-friendly characteristics. In the present study, a salt resistant bacterium, Bacillus subtilis BSN-1, was isolated from arid region in Xinjiang, China, and its effects on salt crystallization during evaporation crystallization of saline-alkali soil solution were examined. It was found that the fermentation products of B. subtilis BSN-1, such as glutamic acid, significantly lowered the pH of saline soil solution because of the ionization of carboxyl. The complexation between Ca2+ and fermentation products inhibited the precipitation of Ca-P compounds as well, since the binding sites supplied for Ca2+ is one or two orders of magnitude than that for HPO42-. Moreover, the increased content of active phosphate is attributed to the chelation and adsorption exerted through carboxyl and amide bonds. These findings demonstrated that Bacillus subtilis BSN-1 suppressed the crystallization of phosphate and therefor increased the content of active phosphate, which may provide a promising solution for amendment and remediation of saline-alkali soil.

Effects of different surface-coated nTiO2 on full-grown carrot plants: Impacts on root splitting, essential elements, and Ti uptake.

The production and environmental release of surface-modified titanium dioxide nanoparticles (nTiO2) have increased. Hence, crops may be directly exposed to the nTiO2 in soil. In this study, we grew carrots in soils amended with pristine, hydrophilic and hydrophobic surface-coated nTiO2 at 100, 200, and 400 mg kg-1 until full-plant maturity. The content of Ti in plant secondary roots treated with different nTiO2 at 400 mg kg-1 was in the order of hydrophobic > hydrophilic > pristine treatments, with values of 140.1, 100.5, and 64.3 mg kg-1, respectively. The fresh biomass of the taproot was significantly decreased by all nTiO2 forms at 400 mg kg-1 by up to 56 %, compared to control. Pristine nTiO2 at 100 mg kg-1 enhanced the fresh weight of leaves by 51 % with respect to control. Remarkably, an abnormal increase of taproot splitting was found in plants treated with all nTiO2 forms. In carrots treated with the surface-coated nTiO2, the accumulation of Ca, Mg, Fe, and Zn increased in leaves; but Mg, Mn, and Zn decreased in taproots. These results suggest that future regulation of nTiO2 release into soils should consider its surface coating properties since the phytotoxicity effects depend on nTiO2 outer structure.

Dysfunction of estrogen-related receptor alpha-dependent hepatic VLDL secretion contributes to sex disparity in NAFLD/NASH development.

Rationale: Men and postmenopausal women are more prone to developing non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) than premenopausal women. However, the pathological links and underlying mechanisms of this disparity are still elusive. The sex-difference in hepatic very low-density lipoprotein (VLDL) assembly and secretion may contribute to NAFLD development. Estrogen-related receptor alpha (ERRα) is a key regulator of several metabolic processes. We hypothesized that ERRα plays a role contributing to the sex-difference in hepatic VLDL assembly and secretion. Methods: VLDL secretion and essential genes governing said process were assessed in male and female mice. Liver-specific ERRα-deficient (ERRαLKO) mice were generated to assess the rate of hepatic VLDL secretion and alteration in target gene expression. Overexpression of either microsomal triglyceride transfer protein (Mttp) or phospholipase A2 G12B (Pla2g12b) by adenovirus was performed to test if the fatty liver phenotype in male ERRαLKO mice was due to defects in hepatic VLDL secretion. Female ERRαLKO mice were put on a diet high in saturated fat, fructose and cholesterol (HFHC) to promote NASH development. Wild type female mice were either ovariectomized or treated with tamoxifen to induce a state of estrogen deficiency or disruption in estrogen signaling. Adenovirus was used to overexpress ERRα in these mice to test if ERRα was sufficient to rescue the suppressed VLDL secretion due to estrogen dysfunction. Finally, wild type male mice on a high-fat diet (HFD) were treated with an ERRα inverse agonist to assess if suppressing ERRα activity pharmacologically would lead to fatty liver development. Results: ERRα is an indispensable mediator modulating hepatic triglyceride-rich very low-density lipoprotein (VLDL-TG) assembly and secretion through coordinately controlling target genes apolipoprotein B (Apob), Mttp and Pla2g12b in a sex-different manner. Hepatic VLDL-TG secretion is blunted in ERRαLKO mice, leading to hepatosteatosis which exacerbates endoplasmic reticulum stress and inflammation paving ways for NASH development. Importantly, ERRα acts downstream of estrogen/ERα signaling in contributing to the sex-difference in hepatic VLDL secretion effecting hepatic lipid homeostasis. Conclusions: Our results highlight ERRα as a key mediator which contributes to the sex disparity in NAFLD development, suggesting that selectively restoring ERRα activity in the liver may be a novel strategy for treating NAFLD/NASH.

Improvement of nutrient elements and allicin content in green onion (Allium fistulosum) plants exposed to CuO nanoparticles.

With the exponential growth of nanomaterial production in the last years, nano copper (Cu)-based compounds are gaining more consideration in agriculture since they can work as pesticides or fertilizers. Chinese scallions (Allium fistulosum), which are characterized by their high content of the antioxidant allicin, were the chosen plants for this study. Spectroscopic and microscopic techniques were used to evaluate the nutrient element, allicin content, and enzyme antioxidant properties of scallion plants. Plants were harvested after growing for 80 days at greenhouse conditions in soil amended with CuO particles [nano (nCuO) and bulk (bCuO)] and CuSO4 at 75-600 mg/kg]. Two-photon microscopy images demonstrated the particulate Cu uptake in nCuO and bCuO treated roots. In plants exposed to 150 mg/kg of the Cu-based compounds, root Cu content was higher in plants treated with nCuO compared with bCuO, CuSO4, and control (p ≤ 0.05). At 150 mg/kg, nCuO increased root Ca (86%), root Fe (71%), bulb Ca (74%), and bulb Mg (108%) content, compared with control (p ≤ 0.05). At the same concentration, bCuO reduced root Ca (67%) and root Mg (33%), compared with control (p ≤ 0.05). At all concentrations, nCuO and CuSO4 increased leaf allicin (56-187% and 42-90%, respectively), compared with control (p ≤ 0.05). The antioxidant enzymes were differentially affected by the Cu-based treatments. Overall, the data showed that nCuO enhances nutrient and allicin contents in scallion, which suggests they might be used as a nanofertilizer for onion production.

Development status among infants at ages of 0 to 36 months in Xiaoshan District / 预防医学

Objective@#To learn the status and influencing factors of development among infants at ages of 0 to 36 months in Xiaoshan District, Hangzhou City, so as to provide the reference for promoting healthy development of infants.@*Methods@#Infants at ages of 0-36 months who underwent physical examination in Child Health Clinic of Xiaoshan District Community Health Service Center were selected in 2022. General data of infants and their mothers were collected through questionnaires, and the development status of infants was screened by Age and Stages Questionnaire (third edition). Factors affecting the development status were identified using a multivariable logistic regression model.@*Results@#A total of 2 519 infants were investigated, including 1 339 males (53.16%) and 1 180 females (46.84%). There were 608 infants with abnormal development of at least one functional area of communication (CM), gross motor (GM), fine motor (FM), problems solving (CG) and personal-social (PS). The abnormal rate was 24.14%, and the abnormal rates of the above functional areas were 9.77%, 6.59%, 7.98%, 6.39% and 9.33%, respectively. Multivariable logistic regression analysis showed that gender (male, OR=1.563, 95%CI: 1.191-2.052), mother's childbearing age (≥35 years, OR=1.411, 95%CI: 1.001-1.988), mother's educational level (lower than junior college, OR=1.460, 95%CI: 1.116-1.912) were factors affecting abnormal development of CM; preterm birth (OR=2.323, 95%CI: 1.315-4.103) was factors affecting abnormal development of GM; gender (male, OR=1.654, 95%CI: 1.225-2.232) was factors affecting abnormal development of FM; gender (male, OR=1.511, 95%CI: 1.086-2.102) and mode of delivery (cesarean section, OR=1.460, 95%CI: 1.060-2.010) were factors affecting abnormal development of CG; gender (male, OR=1.340, 95%CI: 1.019-1.763) and birth weight (low birth weight, OR=1.985, 95%CI: 1.149-3.432) were factors affecting abnormal development of PS.@*Conclusions@#The rate of abnormal development among infants at ages of 0 to 36 months in Xiaoshan District is 24.14%. Gender, preterm birth, mode of delivery, birth weight, mother's childbearing age and mother's educational level could affect the development status of infants.

Novel bisthienylethenes containing naphthalimide as the center ethene bridge: photochromism and solvatochromism for combined NOR and INHIBIT logic gates.

Two novel photochromic bisthienylethene derivatives BTE-NA1 and BTE-NA2 with a six-membered aryl ring of naphthalimide fluorescent moiety as the center ethene bridging unit were synthesized and fully characterized by 1H NMR, 13C NMR, and HRMS. They exhibit considerably high cyclization quantum yield and good fatigue resistance. Interestingly, the fluorescence of BTE-NA1 arising from the naphthalimide unit could be well modulated by photochromism and solvatochromism. Quantum chemical calculations were carried out to study their geometrical, electronic, and optical properties, which were in good accordance with the experimental data. Furthermore, a combined NOR and INHIBIT logic operation based on BTE-NA1 has been successfully mimicked with fluorescence changes as outputs.

Differential effects of copper nanoparticles/microparticles in agronomic and physiological parameters of oregano (Origanum vulgare).

The effects of metallic copper nanoparticles (nCu) in plants are not well understood. In this study, soil grown oregano (Origanum vulgare) was exposed for 60days to nCu and Cu microparticles (µCu) at 0-200mgCu/kg. At harvest, Cu accumulation, biomass production, nutrient composition, and Cu fractions in soil were measured. Except for µCu at 50mg/kg, both nCu and µCu increased root Cu (28.4-116.0%) and shoot Cu (83.0-163.0% and 225.4-652.5%, respectively), compared with control. Copper accumulation from µCu increased as the external µCu increased. nCu and µCu did not affect shoot length, malondialdehyde, or chlorophyll, but increased water content (6.9-12.5%) and reduced shoot biomass (21.6-58.5%), compared with control. In addition, at 50mg/kg, µCu decreased root biomass and length (48.6% and 20.5%, respectively) and water content (1.8% and 3.9% at 100 and 200mg/kg, respectively). All treatments modified root and shoot Ca, Fe, Mg, and Mn (p≤0.05). Additionally, all Cu treatments decreased starch (33.9-58.5%), total sugar (39.5-55.7%), and reducing sugar (13.6-33.9%) in leaves. Results showed that metallic Cu nanoparticles/microparticles affected agronomical and physiological parameters in oregano, which could impact human nutrition. However, smaller size particles do not necessarily imply greater toxicity.

Effects of the exposure of TiO2 nanoparticles on basil (Ocimum basilicum) for two generations.

There is a lack of information about the transgenerational effects of titanium dioxide nanoparticles (nano-TiO2) in plants. This study aimed to evaluate the impacts of successive exposure of nano-TiO2 with different surface properties to basil (Ocimum basilicum). Seeds from plants exposed or re-exposed to pristine, hydrophobic, or hydrophilic nano-TiO2 were cultivated for 65 days in soil unamended or amended with 750 mg·kg-1 of the respective particles. Plant growth, concentration of titanium and essential elements, as well as content of carbohydrates and chlorophyll were evaluated. There were no differences on Ti concentration in roots of plants sequentially exposed to pristine or hydrophobic nano-TiO2, or in roots of plants exposed to the corresponding particle, only in the second cycle. However, sequential exposure to hydrophilic particles resulted in 65.2% less Ti in roots, compared to roots of plants exposed the same particles, only in the second cycle. The Ti concentrations in shoots were similar in all treatments. On the other hand, pristine and hydrophilic particles reduced Mg in root by 115% and 81%, respectively, while pristine and hydrophobic particles reduced Ni in shoot by 84% and 75%, respectively, compared to unexposed plants in both cycles. Sequential exposure to pristine nano-TiO2 increased stomatal conductance (214%, p ≤ 0.10), compared to plants that were never exposed. Hydrophobic and hydrophilic nano-TiO2 reduced chlorophyll b (52%) and total chlorophyll (30%) but increased total sugar (186%) and reducing sugar (145%), compared to unexposed plants in both cycles. Sequential exposure to hydrophobic or hydrophilic nano-TiO2 resulted in more adverse effects on photosynthesis but in positive effects on plant growth, compared to pristine nano-TiO2.

Foliar Exposure of Cu(OH)2 Nanopesticide to Basil ( Ocimum basilicum): Variety-Dependent Copper Translocation and Biochemical Responses.

In this study, low and high anthocyanin basil ( Ocimum basilicum) varieties (LAV and HAV) were sprayed with 4.8 mg Cu/per pot from Cu(OH)2 nanowires, Cu(OH)2 bulk (CuPro), or CuSO4 and cultivated for 45 days. In both varieties, significantly higher Cu was determined in leaves of CuSO4 exposed plants (691 and 672.6 mg/kg for LAV and HAV, respectively); however, only in roots of HAV, Cu was higher, compared to control ( p ≤ 0.05). Nanowires increased n-decanoic, dodecanoic, octanoic, and nonanoic acids in LAV, but reduced n-decanoic, dodecanoic, octanoic, and tetradecanoic acids in HAV, compared with control. In HAV, all compounds reduced eugenol (87%), 2-methylundecanal (71%), and anthocyanin (3%) ( p ≤ 0.05). In addition, in all plant tissues, of both varieties, nanowires and CuSO4 reduced Mn, while CuPro increased chlorophyll contents, compared with controls ( p ≤ 0.05). Results suggest that the effects of Cu(OH)2 pesticides are variety- and compound-dependent.

Methylation dictates PI.f-specific CYP19 transcription in human glial cells.

CYP19 is the single copy gene encoding for the estrogen synthetic enzyme aromatase. Alternate splicing of the promoter is the regulatory mechanism of this gene. In the brain, estrogen is synthesized in neuronal and glial cells and the gene is mainly regulated by the alternate promoter PI.f. The hormone produced in this vicinity has been associated with maintaining normal brain functions. Previously, epigenetic regulation has been shown in the promoters PII and I.3 of CYP19 in adipocytes. In the present study, the methylation of PI.f in CYP19 was examined in glial cells. Treatment of the hypomethylating agent 5-aza-2'deoxycytidine increased CYP19 mRNA species in U87 MG cells while little changes were observed in the other glia cell lines. As PI.f is also chiefly used in T98G cells with high expression of CYP19, the methylation statuses of the promoter in these two cell models were compared. Our results showed that treating U87 MG cells with 10 µM 5-aza-2'deoxycytidine significantly induced a ∼10-fold increase in CYP19 transcription and ∼80% increase in aromatase activity. In contrast, the same treatment did not change either endpoint in T98G cells. Further investigation illustrated the CpGs in PI.f were differentially methylated in the two cell lines; 63% and 37% of the 14 CpG sites were methylated in U87 MG and T98G cells respectively. In conclusion, this study illustrated that the brain-specific PI.f derived CYP19 expression can be regulated by DNA methylation.

Interaction of metal oxide nanoparticles with higher terrestrial plants: Physiological and biochemical aspects.

Multiple applications of metal oxide nanoparticles (MONPs) could result in their accumulation in soil, threatening higher terrestrial plants. Several reports have shown the effects of MONPs on plants. In this review, we analyze the most recent reports about the physiological and biochemical responses of plants to stress imposed by MONPs. Findings demonstrate that MONPs may be taken up and accumulated in plant tissues causing adverse or beneficial effects on seed germination, seedling elongation, photosynthesis, antioxidative stress response, agronomic, and yield characteristics. Given the importance of determining the potential risks of MONPs on crops and other terrestrial higher plants, research questions about field long-term conditions, transgenernational phytotoxicity, genotype specific sensitivity, and combined pollution problems should be considered.

Physiological and biochemical effects of nanoparticulate copper, bulk copper, copper chloride, and kinetin in kidney bean (Phaseolus vulgaris) plants.

It is essential to understand the interactions of engineered nanoparticles (ENPs) with additives used in agriculture and their impacts on crop plants. In this study, kidney bean (Phaseolus vulgaris) plants were grown in potting soil amended with either nano copper (nCu), bulk copper (bCu), or copper chloride (CuCl2) at 0, 50, and 100mg/kg, combined with 0, 10, or 100µM of kinetin (KN). Plant growth, Cu, micro and macroelement concentrations, chlorophyll content, and enzymatic activity were examined in 55-day old plants. Results showed that root Cu content was at least 10-fold higher, compared to other tissues. Accumulation of Cu in roots was decreased by 100µM KN up to 25%. A concentration-dependent increase of Cu content in leaves by Cu×KN was observed. Chlorophyll production was diminished by CuCl2+KN between 22 and 30%, showing a hormetic response. Catalase activity was repressed by 65% to 82% in bCu and CuCl2 treatments. From all essential elements, Ca, Mn, and P were reduced by 33% to 97% in bCu, CuCl2, and CuCl2+KN treatments. However, this did not impact stem elongation and tissue biomass that increased up to 55% under exposure to bCu and CuCl2. Our results demonstrate that KN combined with ionic Cu could have negative implications in kidney bean plants, since this combination impacted chlorophyll production and nutrient element accumulation.

[Depression and anxiety caused by pegylated interferon treatment in patients with chronic hepatitis B and the therapeutic effects of escitalopram and alprazolam].

OBJECTIVE: To evaluate the incidence of depression and anxiety caused by pegylated interferon α (PegIFN-α) treatment for chronic hepatitis B (CHB) and assess the efficacy of intervention with escitalopram and alprazolam. METHODS: A total of 165 CHB patients receiving PegIFN-α-based treatment for 12 weeks were assessed for moderate to severe depression and anxiety using Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7)]. The patients identified to have moderate to severe depression and anxiety treated with escitalopram or alprazolam and the psychological condition of the patients was assessed at the 2nd, 4th and 8th weeks of the treatments. RESULTS: In the 165 patients receiving PegIFN-α treatment, 51 patients developed moderate to severe psychiatric symptoms, incuding 37 (22.4%) with depression, 31 (18.8%) with anxiety, and 17 (10.3%) with both. The symptoms of depression and anxiety was both significantly improved by intervention with escitalopram (P=0.000); alprazolam was effective for anxiety (P=0.001) but did not produce obvious effects on depression (P=0.904). Nevertheless, alprazolam had a much better therapeutic effect than escitalopram on anxiety in these patients (t=-3.198, P=0.010). CONCLUSION: Psychological symptoms are common in CHB patients receiving PegIFN-α treatment. The symptoms of depression and anxiety can be ameliorated by intervention with escitalopram and alprazolam, respectively.

Synthesis and biological evaluations of chalcones, flavones and chromenes as farnesoid x receptor (FXR) antagonists.

Farnesoid X receptor (FXR), a nuclear receptor mainly distributed in liver and intestine, has been regarded as a potential target for the treatment of various metabolic diseases, cancer and infectious diseases related to liver. Starting from two previously identified chalcone-based FXR antagonists, we tried to increase the activity through the design and synthesis of a library containing chalcones, flavones and chromenes, based on substitution manipulation and conformation (ring closure) restriction strategy. Many chalcones and four chromenes were identified as microM potent FXR antagonists, among which chromene 11c significantly decreased the plasma and hepatic triglyceride level in KKay mice.

Surface coating changes the physiological and biochemical impacts of nano-TiO2 in basil (Ocimum basilicum) plants.

Little is known about the effects of surface coating on the interaction of engineered nanoparticles (ENPs) with plants. In this study, basil (Ocimum basilicum) was cultivated for 65 days in soil amended with unmodified, hydrophobic (coated with aluminum oxide and dimethicone), and hydrophilic (coated with aluminum oxide and glycerol) titanium dioxide nanoparticles (nano-TiO2) at 125, 250, 500, and 750 mg nano-TiO2 kg-1 soil. ICP-OES/MS, SPAD meter, and UV/Vis spectrometry were used to determine Ti and essential elements in tissues, relative chlorophyll content, carbohydrates, and antioxidant response, respectively. Compared with control, hydrophobic and hydrophilic nano-TiO2 significantly reduced seed germination by 41% and 59%, respectively, while unmodified and hydrophobic nano-TiO2 significantly decreased shoot biomass by 31% and 37%, respectively (p ≤ 0.05). Roots exposed to hydrophobic particles at 750 mg kg-1 had 87% and 40% more Ti than the pristine and hydrophilic nano-TiO2; however, no differences were found in shoots. The three types of particles affected the homeostasis of essential elements: at 500 mg kg-1, unmodified particles increased Cu (104%) and Fe (90%); hydrophilic increased Fe (90%); while hydrophobic increased Mn (339%) but reduced Ca (71%), Cu (58%), and P (40%). However, only hydrophobic particles significantly reduced root elongation by 53%. Unmodified, hydrophobic, and hydrophilic particles significantly reduced total sugar by 39%, 38%, and 66%, respectively, compared with control. Moreover, unmodified particles significantly decreased reducing sugar (34%), while hydrophobic particles significantly reduced starch (35%). Although the three particles affected basil plants, coated particles impacted the most its nutritional quality, since they altered more essential elements, starch, and reducing sugars.