Design and synthesis of novel ß-carboline-bisindole hybrids as potential anticancer agents.

We are reporting a short and convenient pathway for the synthesis of novel ß-carboline-bisindole hybrid compounds from relatively cheap and commercially available chemicals such as tryptamine, dialdehydes and indoles. These newly designed compounds can also be prepared in high yields with the tolerance of many functional groups under mild conditions. Notably, these ß-carboline-bisindole hybrid compounds exhibited some promising applications as anticancer agents against the three common cancer cell lines MCF-7 (breast cancer), SK-LU-1 (lung cancer), and HepG2 (liver cancer). The two best compounds 5b and 5g inhibited the aforementioned cell lines with the same range of the reference Ellipticine at less than 2 µM. A molecular docking study to gain more information about the interactions between the synthesized molecules and the kinase domain of the EGFR was performed. Therefore, this finding can have significant impacts on the development of future research in medicinal chemistry and drug discovery.

Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial.

BACKGROUND: Inflamm-aging is associated with the rate of aging and is significantly related to diseases such as Alzheimer's disease, Parkinson's disease, atherosclerosis, heart disease, and age-related degenerative diseases such as type II diabetes and osteoporosis. This study aims to evaluate the safety and efficiency of autologous adipose tissue-derived mesenchymal stem cell (AD-MSC) transplantation in aging-related low-grade inflammation patients. METHODS: This study is a single-group, open-label, phase I clinical trial in which patients treated with 2 infusions (100 million cells i.v) of autologous AD-MSCs were initially evaluated in 12 inflamm-aging patients who concurrently had highly proinflammatory cytokines and 2 of the following 3 diseases: diabetes, dyslipidemia, and obesity. The treatment effects were evaluated based on plasma cytokines. RESULTS: During the study's follow-up period, no adverse effects were observed in AD-MSC injection patients. Compared to baseline (D-44), the inflammatory cytokines IL-1α, IL-1ß, IL-8, IL-6, and TNF-α were significantly reduced after 180 days (D180) of MSC infusion. IL-4/IL-10 at 90 days (D90) and IL-2/IL-10 at D180 increased, reversing the imbalance between proinflammatory and inflammatory ratios in the patients. CONCLUSION: AD-MSCs represent a potential intervention to prevent age-related inflammation in patients. TRIAL REGISTRATION: ClinicalTrials.gov number is NCT05827757, first registered on 13th Oct 2020.

Characterization and biological prospects of various calcined temperature-V2O5 nanoparticles synthesized by Citrus hystrix fruit extract.

In this study, a simple green synthesis of vanadium pentoxide nanoparticles (VNPs) was prepared by the extract of Kaffir lime fruit (Citrus hystrix) as a green reducing and stabilizing agent, along with the investigation of calcination temperature was carried out at 450 and 550 °C. It was affirmed that, at higher temperature (550 °C), the VNPs possessed a high degree crystalline following the construction of (001) lattice diffraction within an increase in crystalline size from 47.12 to 53.51 nm, although the band gap of the materials at 450 °C was lower than that of the VNPs-550 (2.53 versus 2.66 eV, respectively). Besides, the materials were assessed for the potential bioactivities toward antibacterial, antifungal, DNA cleavage, anti-inflammatory, and hemolytic performances. As a result, the antibacterial activity, with minimal inhalation concentration (MIC) < 6.25 µg/mL for both strains, and fungicidal one of the materials depicted the dose-dependent effects. Once, both VNPs exhibited the noticeable efficacy of the DNA microbial damage, meanwhile, the outstanding anti-inflammatory agent was involved with the IC50 of 123.636 and 227.706 µg/mL, accounting for VNPs-450 and VNPs-550, respectively. Furthermore, this study also demonstrated the hemolytic potential of the VNPs materials. These consequences declare the prospects of the VNPs as the smart and alternative material from the green procedure in biomedicine.

A comparison of symptoms and quality of life between medial flap and coblation turbinator of inferior turbinate reduction in endoscopic septoturbinoplasty: an analysis of 108 cases.

Introduction: The combination of septoplasty and turbinoplasty is a common surgical and accepted intervention to correct the nasal obstruction. The coblation submucosal reduction turbinator is a new surgical device, and it started to be used recently. On the other hand, the medial flap inferior turbinoplasty is not a conservative technique, but it provides a reliable and robust reduction. Objective: This study aims to compare the symptoms as well as health-related quality of life (HQOL) in 55 patients who underwent septoplasty with concomitent medial flap inferior turbinoplasty (group 1), 53 patients who patients underwent septoplasty with concomitent coblation turbinator (group 2). Patients and methods: The authors performed a prospective, randomized study of 108 patients who consulted the otorhinolaryngology department at the university hospital for surgery of septoturbinoplasty. Results: Preoperatively, the two patient groups had quite similar symptoms and health-related quality of life, and the anterior width of the inferior turbinate showed significant differences between the contralateral and deviated sides but not the posterior part. The significant difference (P<0.05) was noted for postoperatively improved symptom scores on visual analogue scale (VAS), nasal obstruction septoplasty effectiveness (NOSE) and better HQOL [Sino-Nasal Outcome Test-22 (SNOT-22)] in all patient groups. In addition, the NOSE and SNOT-22 scores in group 2 had significantly greater improvement than group 1 (P<0.05). Conclusions: Septoturbinoplasty treatment of septum deviation and inferior turbinate hypertrophy led to less symptoms as well as better HQOL for all two patient groups. Therefore, these techniques were an effective intervention for turbinate reduction, and they are equally efficient in the long term.

Longitudinal peanut and Ara h 2 specific-IgE, -IgG4, and -IgG4/-IgE ratios are associated with the natural resolution of peanut allergy in childhood.

BACKGROUND: There are no studies of longitudinal immunoglobulin measurements in a population-based cohort alongside challenge-confirmed peanut allergy outcomes. Little is known about biomarkers for identifying naturally resolving peanut allergy during childhood. OBJECTIVES: To measure longitudinal trends in whole peanut and component Ara h 2 sIgE and sIgG4 in the first 10 years of life, in a population cohort of children with challenge-confirmed peanut allergy, and to determine whether peanut-specific immunoglobulin levels or trends are associated with peanut allergy persistence or resolution by 10 years of age. METHODS: One-year-old infants with challenge-confirmed peanut allergy (n = 156) from the HealthNuts study (n = 5276) were prospectively followed at ages 4, 6, and 10 years with questionnaires, skin prick tests, oral food challenges, and plasma total-IgE, sIgE and sIgG4 to peanut and Ara h 2. RESULTS: Peanut allergy resolved in 33.9% (95% CI = 25.3%, 43.3%) of children by 10 years old with most resolving (97.4%, 95% CI = 86.5%, 99.9%) by 6 years old. Decreasing Ara h 2 sIgE (p = .01) and increasing peanut sIgG4 (p < .001), Ara h 2 sIgG4 (p = .01), peanut sIgG4/sIgE (p < .001) and Ara h 2 sIgG4/sIgE (p < .001) from 1 to 10 years of age were associated with peanut allergy resolution. Peanut sIgE measured at 1 year old had the greatest prognostic value (AUC = 0.75 [95% CI = 0.66, 0.82]); however, no single threshold produced both high sensitivity and specificity. CONCLUSION: One third of infant peanut allergy resolved by 10 years of age. Decreasing sIgE and sIgG4 to peanut and Ara h 2 over time were associated with natural resolution of peanut allergy. However, biomarker levels at diagnosis were not strongly associated with the natural history of peanut allergy.

xCAPT5: protein-protein interaction prediction using deep and wide multi-kernel pooling convolutional neural networks with protein language model.

BACKGROUND: Predicting protein-protein interactions (PPIs) from sequence data is a key challenge in computational biology. While various computational methods have been proposed, the utilization of sequence embeddings from protein language models, which contain diverse information, including structural, evolutionary, and functional aspects, has not been fully exploited. Additionally, there is a significant need for a comprehensive neural network capable of efficiently extracting these multifaceted representations. RESULTS: Addressing this gap, we propose xCAPT5, a novel hybrid classifier that uniquely leverages the T5-XL-UniRef50 protein large language model for generating rich amino acid embeddings from protein sequences. The core of xCAPT5 is a multi-kernel deep convolutional siamese neural network, which effectively captures intricate interaction features at both micro and macro levels, integrated with the XGBoost algorithm, enhancing PPIs classification performance. By concatenating max and average pooling features in a depth-wise manner, xCAPT5 effectively learns crucial features with low computational cost. CONCLUSION: This study represents one of the initial efforts to extract informative amino acid embeddings from a large protein language model using a deep and wide convolutional network. Experimental results show that xCAPT5 outperforms recent state-of-the-art methods in binary PPI prediction, excelling in cross-validation on several benchmark datasets and demonstrating robust generalization across intra-species, cross-species, inter-species, and stringent similarity contexts.

Electro-Nuclear Dynamics of Single and Double Ionization of H2 in Ultrafast Intense Laser Pulses.

We present an efficient method for modeling the single and double ionization dynamics of the H2 molecule in ultrashort, intense laser fields. This method is based on a semianalytical approach to calculate the time-dependent single and double molecular ionization rates and on a numerical approach to describe the vibrational motion that takes place in the intermediate molecular ion H2+. This model allows for the prediction of the single and double ionization probabilities of the H2 molecule to be made over a wide range of frequencies and laser intensities with limited computational time while providing a realistic estimate of the energy of the products of the dissociative ionization and of the Coulomb explosion of the H2 molecule. The effect of vibrational dynamics on ionization yields and proton kinetic energy release spectra is demonstrated and, in the case of the latter, is discussed in terms of basic strong-field molecular fragmentation mechanisms.

Pancreatic metastasis of mesenchymal chondrosarcoma: a surgical case report and review of literature.

Introduction: Mesenchymal chondrosarcoma (MC) is a rapidly progressive sarcoma that predominantly impacts the bones. Making up only 3% of chondrosarcomas, about one-third of these tumours develop in extra-skeletal sites. Case presentation: The authors present a clinical case of a 42-year-old patient who was diagnosed with MC 8 years ago, now admitted to the hospital with a palpable epigastric mass. Clinical and laboratory examinations showed consistent results for MC tumours, with metastasis to the body and tail of the pancreas and invasion of the splenic vein. Surgical resection and systemic screening were performed to ensure that there were no lesions elsewhere. Regular follow-up has found no localized lesions or complications after 15 months. Clinical discussion: Metastatic extra-skeletal mesenchymal chondrosarcoma of the pancreas is exceptionally rare. To our current understanding, only 14 such cases have been documented in medical literature. The symptoms of pancreatic metastasis are diverse and the radiographic features of metastatic mesenchymal chondrosarcoma are not typically distinct. Conclusions: Although MC tumours do not frequently occur in sites other than the axial system, a tumour presenting later in a patient with a history of MC should be reviewed to confirm the diagnosis of metastatic MC. Treatment can vary between surgery, radiation therapy and systemic therapy.

The ability of a 3-gene host signature in blood to distinguish tuberculous meningitis from other brain infections.

BACKGROUND: Tuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections. METHODS: The expression of 3 genes (Dual specificity phosphatase 3- DUSP3, Guanylate-binding protein- GBP5, Krupple-like factor 2- KLF2) was analysed by RNA sequencing of archived whole blood from four cohorts of Vietnamese adults: 281 with TBM; 279 with pulmonary tuberculosis; 50 with other brain infections; and 30 healthy controls. 'TB scores' (combined 3-gene expression) were calculated following published methodology and discriminatory performance compared using area under a receiver operator characteristic curve (AUC). RESULTS: GBP5 was upregulated in TBM compared to other brain infections (p < 0.001), with no difference in DUSP3 and KLF2 expression. The diagnostic performance of GBP5 alone (AUC 0.74 (95% CI 0.67-0.81)) was slightly better than the 3-gene TB score (AUC 0.66, 95% CI 0.58-0.73) in TBM. Both GBP5 expression and TB score were higher in HIV-positive participants (P < 0.001), with good diagnostic performance of GBP5 alone (AUC 0.86, 95% CI 0.80-0.93). CONCLUSION: The 3-gene host signature in whole blood has the ability to discriminate TBM from other brain infections, including in HIV-positive individuals. Validation in large prospective diagnostic study is now required.

Annona glabra L. Seeds: An Agricultural Waste Biosorbent for the Eco-Friendly Removal of Methylene Blue.

The seeds of Annona glabra L., an invasive plant in Vietnam, were first employed as a new biosorbent for the adsorption of methylene blue (MB) from aqueous media. The characterizations of the material using FT-IR, SEM, nitrogen adsorption-desorption analysis, and point of zero charge reveals that it possesses a rough and irregular surface, various polar functional groups, and pHpzc of 5.5. Certain adsorption conditions including adsorbent dose, solution pH, contact time, and initial concentration of MB were found to affect adsorption efficiency. The kinetic data are well fitted with pseudo-second-order model with the adsorption rate of 0.002 g mg-1 min-1 and initial rate of 4.46 mg g-1 min-1. For the adsorption isotherm, three nonlinear models were used to analyze the experiment data, including Langmuir, Freundlich, and Temkin. The results indicate that the Langmuir model best describes the adsorption of Annona glabra L. seeds powder (AGSP) with a maximum adsorption capacity of 98.0 mg g-1. The investigation underpins the adsorption mechanism, whereby the electrostatic attraction between positively charged MB and negatively charged surface of AGSP is expected to be the predominant mechanism, together with hydrogen bonding and pi-pi interaction. These results make AGSP an interesting biosorbent concerning its environmental friendliness, cost-effectiveness, and relatively high dye adsorption capacity.

Risk for Seasonal Affective Disorder (SAD) Linked to Circadian Clock Gene Variants.

Molecular pathways affecting mood are associated with circadian clock gene variants and are influenced, in part, by the circadian clock, but the molecular mechanisms underlying this link are poorly understood. We use machine learning and statistical analyses to determine the circadian gene variants and clinical features most highly associated with symptoms of seasonality and seasonal affective disorder (SAD) in a deeply phenotyped population sample. We report sex-specific clock gene effects on seasonality and SAD symptoms; genotypic combinations of CLOCK3111/ZBTB20 and PER2/PER3B were significant genetic risk factors for males, and CRY2/PER3C and CRY2/PER3-VNTR were significant risk factors for females. Anxiety, eveningness, and increasing age were significant clinical risk factors for seasonality and SAD for females. Protective factors for SAD symptoms (in females only) included single gene variants: CRY1-GG and PER3-VNTR-4,5. Clock gene effects were partially or fully mediated by diurnal preference or chronotype, suggesting multiple indirect effects of clock genes on seasonality symptoms. Interestingly, protective effects of CRY1-GG, PER3-VNTR-4,5, and ZBTB20 genotypes on seasonality and depression were not mediated by chronotype, suggesting some clock variants have direct effects on depressive symptoms related to SAD. Our results support previous links between CRY2, PER2, and ZBTB20 genes and identify novel links for CLOCK and PER3 with symptoms of seasonality and SAD. Our findings reinforce the sex-specific nature of circadian clock influences on seasonality and SAD and underscore the multiple pathways by which clock variants affect downstream mood pathways via direct and indirect mechanisms.

Late-Onset Melorheostosis: A Case Report.

Melorheostosis is a rare benign bone pathology involving bone dysplasia and hyperostosis. The disease can be recognized with a characteristic radiographic feature of radiopaque lesions dripping along a long bone's diaphysis. The aberrant bone formation and development manifests mainly as pain, edema, and paresthesia of the affected limb. Severe cases may report limb deformity as well as limited range of motion. Until now, there have been approximately 300 cases reported about melorheostosis worldwide and its diverse clinical picture and age distribution. In Vietnam, there is only one known case of melorheostosis discovered incidentally via radiography. The scarcity of cases presents a challenge within the medical community in recognizing and diagnosing the condition, and a delayed diagnosis can lead to severe contracture and compromised limb motility. In this article, we reported an 82-year-old case of polyostotic melorheostosis with late onset and predominant edema, affecting the sternum, the ribs, and multiple bones of the right extremities and presented our clinical approach for a geriatric patient with chronic limb edema. Our case is distinctive in terms of anatomical location as well as the predominant 20-year non-pitting edema. A prompt diagnosis was made upon the classic dripping candle wax radiographic features emphasizing the role of plain X-ray in establishing the diagnosis without extraneous utilization of other modalities and invasive procedures. Exclusion of other causes of chronic edema such as lymphadenopathy, malignancy as well as parasitic infection is of clinical importance.

Telemedicine in home-based care for COVID-19 patients.

BACKGROUND: The COVID-19 pandemic has made devastating impacts on public health and global economy. While most people experience mild symptoms, it is highly transmissible and deadly in at-risk populations. Telemedicine has the potential to prevent hospitalization and provide remote care. METHODS: This retrospective study included 336 people with COVID-19, among which 141 (42%) and 195 (58%) were in Delta and Omicron dominant groups, respectively. Patients were confirmed to have COVID-19 by PCR or rapid test and were cared for via telemedicine. Severe cases were hospitalized for more intensive treatment.  RESULTS: The majority of individuals recovered at home (97.02%), while 2.98% required hospitalization. All hospital admissions were in Delta dominant group. No deaths were reported. Delta dominant group was more likely to develop loss of taste and smell, decreased appetite and need longer treatment time than those in Omicron dominant group. CONCLUSIONS: Telemedicine is a safe measure to provide at-home care for people with COVID-19 infections caused by both Delta and Omicron variants. TRIAL REGISTRATION: This study was approved by the Institutional Review Board Committee of University of Medicine and Pharmacy at Ho Chi Minh City (IRB No: 22115-DHYD).

Revisiting the hydrolysis of ampicillin catalyzed by Temoneira-1 ß-lactamase, and the effect of Ni(II), Cd(II) and Hg(II).

ß-Lactamases grant resistance to bacteria against ß-lactam antibiotics. The active center of TEM-1 ß-lactamase accommodates a Ser-Xaa-Xaa-Lys motif. TEM-1 ß-lactamase is not a metalloenzyme but it possesses several putative metal ion binding sites. The sites composed of His residue pairs chelate borderline transition metal ions such as Ni(II). In addition, there are many sulfur-containing donor groups that can coordinate soft metal ions such as Hg(II). Cd(II) may bind to both types of the above listed donor groups. No significant change was observed in the circular dichroism spectra of TEM-1 ß-lactamase on increasing the metal ion content of the samples, with the exception of Hg(II) inducing a small change in the secondary structure of the protein. A weak nonspecific binding of Hg(II) was proven by mass spectrometry and 119m Hg perturbed angular correlation spectroscopy. The hydrolytic process of ampicillin catalyzed by TEM-1 ß-lactamase was described by the kinetic analysis of the set of full catalytic progress curves, where the slow, yet observable conversion of the primary reaction product into a second one, identified as ampilloic acid by mass spectrometry, needed also to be considered in the applied model. Ni(II) and Cd(II) slightly promoted the catalytic activity of the enzyme while Hg(II) exerted a noticeable inhibitory effect. Hg(II) and Ni(II), applied at 10 µM concentration, inhibited the growth of E. coli BL21(DE3) in M9 minimal medium in the absence of ampicillin, but addition of the antibiotic could neutralize this toxic effect by complexing the metal ions.

BNT162b2 COVID-19 vaccination in children alters cytokine responses to heterologous pathogens and Toll-like receptor agonists.

Background: Vaccines can have beneficial off-target (heterologous) effects that alter immune responses to, and protect against, unrelated infections. The heterologous effects of COVID-19 vaccines have not been investigated in children. Aim: To investigate heterologous and specific immunological effects of BNT162b2 COVID-19 vaccination in children. Methods: A whole blood stimulation assay was used to investigate in vitro cytokine responses to heterologous stimulants (killed pathogens, Toll-like receptor ligands) and SARS-CoV-2 antigens. Samples from 29 children, aged 5-11 years, before and 28 days after a second BNT162b2 vaccination were analysed (V2 + 28). Samples from eight children were analysed six months after BNT162b2 vaccination. Results: At V2 + 28, interferon-γ and monocyte chemoattractant protein-1 responses to S. aureus, E. coli, L. monocytogenes, BCG vaccine, H. influenzae, hepatitis B antigen, poly(I:C) and R848 stimulations were decreased compared to pre-vaccination. For most of these heterologous stimulants, IL-6, IL-15 and IL-17 responses were also decreased. There were sustained decreases in cytokine responses to viral, but not bacterial, stimulants six months after BNT162b2 vaccination. Cytokine responses to irradiated SARS-CoV-2, and spike glycoprotein subunits (S1 and S2) were increased at V2 + 28 for most cytokines and remained higher than pre-vaccination responses 6 months after BNT162b2 vaccination for irradiated SARS-CoV-2 and S1. There was no correlation between BNT162b2 vaccination-induced anti-SARS-CoV2-receptor binding domain IgG antibody titre at V2 + 28 and cytokine responses. Conclusions: BNT162b2 vaccination in children alters cytokine responses to heterologous stimulants, particularly one month after vaccination. This study is the first to report the immunological heterologous effects of COVID-19 vaccination in children.

Establishment of cancer cell line originating from a patient with high-grade serous ovarian carcinoma.

Aim: Ovarian cancer is a serious malignancy with high prevalence and mortality. Methods: We isolated and characterized an ovarian high-grade serous cancer cell line (M4) from a tumor of a Vietnamese patient with ovarian carcinoma. Results: The M4 cancer cell line showed good proliferation and stability in culture. Morphologically, the M4 cells showed similar characteristics to tumor cells such as a polyhedral shape, large irregular nuclei, high nuclear/cytoplasmic ratio, high nuclear density and expressing cancer markers like CA125, p53 and Ki67 markers. Conclusion: We have successfully isolated and characterized the M4 cell line from a Vietnamese patient with ovarian carcinoma.

New Guaiane-Type Sesquiterpene and Norsesquiterpene from Alisma plantago-aquatica and Their Xanthine Oxidase Inhibitory Activity.

A new sesquiterpene (1) and a new norsesquiterpene (2) belonging guaiane-type skeleton together with six known compounds (3-8) were isolated from the rhizomes of Alisma plantago-aquatica. Their structures were determined by HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Absolute configurations of new compounds were established by experimental and TD-DFT computational ECD spectra. Compounds 1-8 exhibited xanthine oxidase inhibitory activity with their IC50 values in range of 9.4-66.7 µM. The sesquiterpenoids 1-5 displayed the inhibitory activity and hence they could be potential xanthine oxidase inhibitors from A. plantago-aquatica.

A novel diphenylbutenoid-type compound from the rhizomes of Zingiber montanum (J.Koenig) Link ex A.Dietr. (Zingiberaceae).

From the EtOAc-soluble extract of the rhizomes of Zingiber montanum (J.Koenig) Link ex A.Dietr., a novel diphenylbutenoid, montadinin A (1) and a previously unreported phenylbutenoid compound, 1-(3,4-dimethoxyphenyl)but-3-en-2-ol (7), in natural source were isolated. Additionally, seven known phenylbutenoids were also identified. The structures of all compounds were elucidated through NMR spectroscopic interpretation. Compounds cis-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene (2), cis-4-[(E)-3,4-dimethoxystyryl]-3-(2,4,5-trimethoxyphenyl)cyclohex-1-ene (3), trans-3-(3,4,-dimethoxyphenyl)-4-[(E)-2,4,5-trimethoxystyryl]cyclohex-1-ene (5), and cis-3-(3,4-dimethoxyphenyl)-4-[(Z)-2,4,5-trimethoxylstyryl]cyclohex-1-ene (6) showed weak cytotoxicity against HepG2 cells with IC50 values of 122.9, 127.3, 257.5, and 168.5 µM, respectively.

Exploring economic and environmental efficiency in renewable energy utilization: a case study in the Organization for Economic Cooperation and Development countries.

The share of renewable energy has grown significantly in global energy supply, yet the evaluation of renewable energy utilization has remained limited. Hence, this research explored economic and environmental efficiency in renewable energy utilization in 20 OECD (The Organization for Economic Cooperation and Development) countries from 2015 to 2020. The study approached the data envelopment analysis-slack-based measure (DEA-SBM) to evaluate economic efficiency, and the DEA undesirable output to measure environmental efficiency. Four inputs as labor force, gross capital formation, total renewable energy capacity, and share of renewable energy were compared to two desirable outputs as the gross domestic product (GDP), and total energy production in the economic efficiency model. In the environmental efficiency model, the same inputs were evaluated with GDP as the desirable output and CO2 emissions as the undesirable output. The DEA-SBM revealed that Australia, Belgium, Norway, the UK, and the USA were efficient in economic evaluation, whereas DEA undesirable output indicated that Belgium, France, Sweden, the UK, and the USA were efficient in environmental evaluation. The governments are suggested to adjust the resources management since the number of efficient units decreased in the economic assessment while fluctuating in the environmental assessment.

Autophagy Inhibitor Chloroquine Downmodulates Hepatic Stellate Cell Activation and Liver Damage in Bile-Duct-Ligated Mice.

Hepatic stellate cell (HSC) activation via the autophagy pathway is a critical factor in liver fibrogenesis. This study tests the hypothesis that chloroquine (CQ) treatment can prevent autophagy and HSC activation in vitro and in vivo in bile-duct-ligated (BDL) mice. Sham-operated and BDL mice were treated with either PBS or CQ in two 60 mg/kg doses the day (D) before and after surgery. On day 2 (2D), HSCs were isolated, and their biological activities were evaluated by measuring intracellular lipid content, α-sma/collagen, and expression of autophagy lc3, sqstm1/p62 markers. The treatment efficacy on liver function was evaluated with serum albumin, transaminases (AST/ALT), and hepatic histology. Primary HSCs were treated in vitro for 24 h with CQ at 0, 2.5, 5, 10, 30, and 50 µM. Autophagy and HSC activation were assessed after 2D of treatment. CQ treatment improved serum AST/ALT, albumin, and bile duct proliferation in 2D BDL mice. This is associated with a suppression of HSC activation, shown by higher HSC lipid content and collagen I staining, along with the blockage of HSC autophagy indicated by an increase in p62 level and reduction in lc3 staining. CQ 5 µM inhibited autophagy in primary HSCs in vitro by increasing p62 and lc3 accumulation, thereby suppressing their in vitro activation. The autophagy inhibitor CQ reduced HSC activation in vitro and in vivo. CQ improved liver function and reduced liver injury in BDL mice.