Search

Among their many unique biological features, bats are increasingly recognized as a key reservoir of many emerging viruses that cause massive morbidity and mortality in humans. Bats are capable of harboring many of these deadly viruses without any apparent signs of pathology, in a mechanism known as viral disease tolerance. However, the immunological mechanisms behind viral tolerance remain poorly understood. As a non-model organism species, there are very limited research resources and tools available to study bat immunology. In the cave nectar bat Eonycteris spelaea, we have a panel of monoclonal antibodies (mAbs) against major immune markers. An immunophenotyping survey of major immune compartments and barrier sites using these mAbs reveals differences in the immunological landscape of bats., Competing Interests: Declaration of interests L.-F.W. is a member of Paratus Sciences Corporation’s scientific advisory board. L.-F.W., L.Z.H., and A.Y.T.L. are share option holders of Paratus Sciences Corporation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chemotherapy-induced drug resistance remains a major cause of cancer recurrence and patient mortality. ATP binding cassette subfamily B member 1 (ABCB1) transporter overexpression in tumors contributes to resistance, yet current ABCB1 inhibitors have been unsuccessful in clinical trials. To address this challenge, we propose a new strategy using tryptophan as a lead molecule for developing ABCB1 inhibitors. Our idea stems from our studies on bat cells, as bats have low cancer incidences and high ABCB1 expression. We hypothesized that potential ABCB1 substrates in bats could act as competitive inhibitors in humans. By molecular simulations of ABCB1-substrate interactions, we generated a benzylated Cyclo-tryptophan (C3N-Dbn-Trp2) that inhibits ABCB1 activity with efficacy comparable to or better than the classical inhibitor, verapamil. C3N-Dbn-Trp2 restored chemotherapy sensitivity in drug-resistant human cancer cells with no adverse effect on cell proliferation. Our unique approach presents a promising lead toward developing effective ABCB1 inhibitors to treat drug-resistant cancers., (© 2024. The Author(s).)

Bats are special in their ability to live long and host many emerging viruses. Our previous studies showed that bats have altered inflammasomes, which are central players in aging and infection. However, the role of inflammasome signaling in combating inflammatory diseases remains poorly understood. Here, we report bat ASC2 as a potent negative regulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and protein levels and is highly potent in inhibiting human and mouse inflammasomes. Transgenic expression of bat ASC2 in mice reduced the severity of peritonitis induced by gout crystals and ASC particles. Bat ASC2 also dampened inflammation induced by multiple viruses and reduced mortality of influenza A virus infection. Importantly, it also suppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residues were identified for the gain of function of bat ASC2. Our results demonstrate that bat ASC2 is an important negative regulator of inflammasomes with therapeutic potential in inflammatory diseases., Competing Interests: Declaration of interests L.-F.W., M.A., and V.C.-W.C. are co-inventors of a patent application based on findings from the study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study aimed to investigate the effects of caffeine on performances of simulated match, Wingate Anaerobic Test (WAnT), and cognitive function test of elite taekwondo athletes. Ten elite taekwondo athletes in Hong Kong volunteered to participate in two main trials in a randomized double-blinded crossover design. In each main trial, 1 h after consuming a drink with caffeine (CAF) or a placebo drink without caffeine (PLA), the participants completed two simulated taekwondo match sessions followed by the WAnT. The participants were instructed to complete three cognitive function tests, namely the Eriksen Flanker Test (EFT), Stroop Test, and Rapid Visual Information Processing Test, at baseline, before exercise, and immediately after the simulated matches. They were also required to wear functional near-infrared spectroscopy equipment during these tests. Before exercise, the reaction time in the EFT was shorter in the CAF trial than in the PLA trial (PLA: 494.9 ± 49.2 ms vs. CAF: 467.9 ± 38.0 ms, p = 0.035). In the WAnT, caffeine intake increased the peak power and mean power per unit of body weight (by approximately 13% and 6%, respectively, p = 0.018 & 0.042). The performance in the simulated matches was not affected by caffeine intake ( p = 0.168). In conclusion, caffeine intake enhances anaerobic power and may improve certain cognitive functions of elite taekwondo athletes in Hong Kong. However, this may not be enough to improve the simulated match performance.

In this study, the ternary blends of palm kernel oil (PKO), soybean oil (SBO) and two types of palm stearin (PS) (PS33 and PS38) were systematically prepared and evaluated for their application as an alternative to milk fat in frozen dessert. The physicochemical characteristics namely fatty acids constituent, triacylglycerols (TAGs) composition, melting behavior, solid fat content (SFC) and microstructure were studied. All ternary blends of PKO/SBO/PS33 and PKO/SBO/PS38 had comparable microstructure to that of milk fat. However, 80/15/5 (PKO/SBO/PS33) and 80/15/5 to 80/5/15 (PKO/SBO/PS38) mixtures were found to have similar SFC as milk fat at temperature above 20 °C, allowing these ternary blends to be completely melted at body temperature. With this, 80/15/5 (PKO/SBO/PS33) and 80/15/5 to 80/5/15 (PKO/SBO/PS38) mixtures were able to provide similar meltdown and mouth feel as milk fat at room temperature. Nonetheless, fatty acids constituent, TAGs composition and melting behavior of the blends were different from milk fat. This study showed that ternary blends of PKO, SBO and PS at ratios 80/15/5 (PKO/SBO/PS33) and 80/15/5 to 80/5/15 (PKO/SBO/PS38) can be potentially used as a milk fat alternative for frozen dessert application based on its similar microstructure and SFC profile as the milk fat., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05507-z., Competing Interests: Conflict of interestThe authors have no conflict of interest to declare., (© The Author(s) 2022.)

Bats are known natural reservoirs of several highly pathogenic zoonotic viruses, including Hendra virus, Nipah virus, rabies virus, SARS-like coronaviruses, and suspected ancestral reservoirs of SARS-CoV-2 responsible for the ongoing COVID-19 pandemic. The capacity to survive infections of highly pathogenic agents without severe disease, together with many other unique features, makes bats an ideal animal model for studying the regulation of infection, cancer, and longevity, which is likely to translate into human health outcomes. A key factor that limits bat research is lack of breeding bat colonies. To address this need, a captive bat colony was established in Singapore from 19 wild-caught local cave nectar bats. The bats were screened for specific pathogens before the start of captive breeding. Custom-made cages and an optimized diet inclusive of Wombaroo dietary formula, liquid diet, and supplement of fruits enabled the bats to breed prolifically in our facility. Cages are washed daily and disinfected once every fortnight. Bats are observed daily to detect any sick bat or abnormal behavior. In addition, bats undergo a thorough health check once every 3 to 4 mo to check on their overall wellbeing, perform sampling, and document any potential pregnancy. The current colony houses over 80 bats that are successfully breeding, providing a valuable resource for research in Singapore and overseas.

Non-edible bio-oil derived from lignocellulosic biomass could be used as environmentally friendly lubricant-ester base stock for maritime and road-type transportations. However, the use of crude bio-oil with highly oxygenated compounds required further upgrading to yield ester that mimicked the characteristics of Group V base oil (polyolesters). In this study, bio-oil based polyolesters was produced via esterification using green biopolymer alginate acid catalyst (Al-Alg). The bio-oil compounds used were acetic acid (AcA), propionic acid (PrA) and levulinic acid (LA), while polyols such as neopentyl glycol (NPG), trimethylolpropane (TMP) and pentaerythritol (PE) were used. Optimization studies revealed that NPG-PrA ester gave the best ester purity of 100%, with 95% of diester selectivity under optimum conditions of 15 wt% Al-Alg, 8 h, 6:1 PrA:NPG and 140 °C. The produced polyolesters showed potential lube characteristics with viscosity index of 76, kinematic viscosity of 2.3 mm 2 s -1 at 40 °C and oxidative induction time of 15 min at 100 °C. Furthermore, a reusability study of the Al-Alg catalyst indicated high NPG-PrA diester selectivity (above 90%) for 8 consecutive cycles. The physico-chemical properties of spent Al-Alg catalyst were also discussed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology., Competing Interests: Declaration of Interests We declare there is no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Xihuang pill, as a famous traditional Chinese medicine formula, is used for tumor treatment in China. The anti-tumor activities and mechanisms of Xihuang pill still remain unclear., Aim of the Study: The Akt/mTOR signaling pathway plays an important role in mediating cell proliferation and apoptosis in glioblastoma. This study aimed to investigate whether Xihuang pill could potentiate temozolomide-induced apoptosis of glioblastoma U87 and U251 cells in vivo and its underlying mechanisms related to Akt/mTOR pathway., Materials and Methods: Human glioblastoma U87 and U251 xenograft models were established. Immunocytochemistry and Western blot were performed to evaluate the anti-proliferative effect, apoptosis and Akt/mTOR signaling mediators., Results: The results showed that Xihuang pill (0.5, 1 g/kg) or temozolomide (10 mg/kg) treatment alone inhibited tumor growth in glioblastoma U87 and U251 xenografts. When Xihuang pill (1 g/kg) and temozolomide (10 mg/kg) were co-administrated, the activities of antitumor growth were markedly increased. Meanwhile, Xihuang pill (0.5, 1 g/kg) or temozolomide (10 mg/kg) treatment alone decreased the levels of Ki67 and PCNA expression in glioblastoma U87 and U251 xenografts. In combination treatment group, the inhibitory effects on Ki67 and PCNA expression were significantly enhanced in glioblastoma U87 and U251 xenografts compared to temozolomide treatment alone. Examining the apoptotic index by TUNEL assay showed similar results. Furthermore, Xihuang pill markedly down-regulated the Bcl-2/Bax ratio and inhibited the activation of Akt/mTOR pathway in glioblastoma U87 and U251 xenografts. In addition, no significant signs of toxicities were related to Xihuang pill and/or temozolomide treatment., Conclusions: The present study suggested that Xihuang pill might potentiate temozolomide-induced apoptosis of glioblastoma cells in vivo through inhibiting Akt/mTOR-dependent pathway., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nasopharyngeal carcinoma (NPC) patients treated with Helical Tomotherapy (HT) are commonly set up in an extended neck (EN) or a flexed neck (FN) position. This study investigated the dosimetric and set-up accuracy differences between these 2 set-up positions. Twenty NPC patients treated with HT from each set-up position were retrospectively recruited. HT plans were computed using the same target prescription and organs at risks (OARs) constraints for both set-up positions. The doses parameters of the target volumes and OARs were assessed. Daily megavoltage CT images were retrieved to obtain the set-up errors at 4th (C4) and 7th (C7) cervical levels. The mean values of these parameters were compared between the 2 set-up positions. The dose to NP target in FN group was more conformal than EN group, while the conformity of the neck targets in FN group were significantly lower. For the OARs, the temporal lobe, cerebellum, and hippocampus in FN group received significantly lower doses than the EN. However, the optic structures, brain stem, spinal cord, and parotid glands received higher doses in FN group. The systematic errors at C4 and C7 levels in FN group were larger in all translational directions except the ML direction at C7 level. With regard to radiotherapy of NPC patient using helical tomotherapy, FN position reduced doses to intracranial structures but increased doses to optic structures and other structures when compared with the EN position. In terms of set-up accuracy at the neck region, EN position was relatively better., (Copyright © 2020 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Recently studies showed that pregnane X receptor (PXR) was expressed in human brain microvessel endothelial cells and coordinately induced multidrug resistance protein 1 (MDR1) expression. The present study aimed to investigate the regulatory effect of Z-guggulsterone on MDR1 in human brain microvessel endothelial cells, and explored whether it involved modulation of PXR. The results showed that Z-guggulsterone (30 μM) simultaneously inhibited the expression of PXR and MDR1 at 24 h in human brain-derived microvessel endothelial cells (hBDMECs). Meanwhile, the levels of PXR and MDR1 expression were simultaneously reduced in PXR siRNA-transfected hBDMECs; MDR-1 siRNA-transfected hBDMECs showed significant decrease in MDR1 expression, but no change in PXR expression. Furthermore, Z-guggulsterone inhibited the activation of PXR in hBDMECs through decreasing the release of cAMP/PKA. Z-guggulsterone reduced the co-activator SRC-1 expression in hBDMECs, as to prevent the activation of MDR1 gene transcription. In addition, Z-guggulsterone (30 μM) at 24 h significantly inhibited the expression of human constitutive androstane receptor (CAR) protein in hBDMECs. However, after treatment with Z-guggulsterone (≤30 μM), the level of MDR1 reporter gene activity was lower in human PXR-transfected cells than that in human CAR-transfected cells. The inhibition effect of Z-guggulsterones on MDR1 reporter gene activation was gradually enhanced with the increase of human PXR to CAR ratio, which was greater extent than that with the increase of human CAR to hPXR ratio. The present study suggested that Z-guggulsterone down-regulating the efflux function and expression of MDR1 in hBDMECs might be mainly through the PXR-dependent manner., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Natural reservoir hosts can sustain infection of pathogens without succumbing to overt disease. Multiple bat species host a plethora of viruses, pathogenic to other mammals, without clinical symptoms. Here, we detail infection of bat primary cells, immune cells, and cell lines with Dengue virus. While antibodies and viral RNA were previously detected in wild bats, their ability to sustain infection is not conclusive. Old-world fruitbat cells can be infected, producing high titres of virus with limited cellular responses. In addition, there is minimal interferon (IFN) response in cells infected with MOIs leading to dengue production. The ability to support in vitro replication/production raises the possibility of bats as a transient host in the life cycle of dengue or similar flaviviruses. New antibody serology evidence from Asia/Pacific highlights the previous exposure and raises awareness that bats may be involved in flavivirus dynamics and infection of other hosts.

Pretreatment of microalgal biomass possessing rigid cell wall is a critical step for enhancing the efficiency of microalgal biorefinery. However, the conventional pretreatment processes suffer the drawbacks of complex processing steps, long processing time, low conversion efficiency and high processing costs. This significantly hinders the industrial applicability of microalgal biorefinery. The innovative electricity-aid pretreatment techniques serve as a promising processing tool to extensively enhance the release of intracellular substances from microalgae. In this review, application of electric field-based techniques and recent advances of using electrical pretreatments on microalgae cell focusing on pulsed electric field, electrolysis, high voltage electrical discharges and moderate electric field are reviewed. In addition, the emerging techniques integrating electrolysis with liquid biphasic flotation process as promising downstream approach is discussed. This review delivers broad knowledge of the present significance of the application of these methods focusing on the development of electric assisted biomolecules extraction from microalgae., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Catalytic esterification of glycerol with oleic acid (OA) was optimized over hydrophobic mesoporous zirconia-silica heterogeneous acid catalyst (ZrO 2 -SiO 2 -Me&Et-PhSO 3 H) and benchmarked with commercial catalysts (Aquivion and Amberlyst 15) in order to examine the effect of catalyst acidity on conversion, yield and product selectivity. The process optimisation results showed an 80% conversion with a 59.4% glycerol mono-oleate (GMO) and 34.6% glycerol dioleate (GDO) selectivities corresponding to a combined GMO and GDO selectivity of 94.8% at equimolar OA-to-glycerol ratio, 160°C reaction temperature, 5 wt% catalyst concentration with respect to the OA weight and 4 h reaction time. This work reveals that the hydrophobic and mild acidic ZrO 2 -SiO 2 -Me&Et-PhSO 3 H catalyst outperformed Amberlyst 15 and Aquivion with a yield of 82% and GMO selectivity of 60%. It is found that catalyst acidity is a key parameter for catalytic activity and conversion rate. Nevertheless, high acidity/acid strength reduced the product yield in the glycerol esterification of OA.

Purpose: Appendicitis is the most common condition leading to an intra-abdominal operation for a non-obstetric problem in pregnancy. The aim of this study was to examine our experience and to analyze the clinical characteristics and the pregnancy outcomes for appendicitis during pregnancy that was reported in Korea., Methods: We reported 25 cases of appendicitis during pregnancy that were treated at Good Moonhwa Hospital from January 2004 to March 2010. We also analyzed appendicitis during pregnancy reported in Korea between 1970 and 2008 by a review of journals., Results: The incidence of acute appendicitis during pregnancy was one per 568 deliveries. The mean age was 27.92 years old, the gestational stage at the onset of symptoms was the first trimester in 10 patients (40%), the second trimester in 14 patients (56%), and the third trimester in 1 patient (4%). Among the 25 cases, 21 were treated with an open appendectomy and 4 with laparoscopic appendectomies. The postoperative complications were 2 wound infections and 1 spontaneous abortion., Conclusion: Our experience demonstrated that appendectomies on pregnant patients can be successfully performed at secondary hospitals.

Objectives: To evaluate the efficacy and safety of lithium in the treatment of thyrotoxicosis, and to study the dose and serum levels at which therapeutic response occurs., Design: Retrospective study., Setting: Thyroid clinic of a regional hospital in Hong Kong., Patients: Thirteen patients with thyrotoxicosis pending therapy with radioiodine or surgery, in whom thionamides were contra-indicated due to adverse reactions or failure of treatment., Main Outcome Measures: Free thyroxine levels, time to euthyroidism, and side-effects of lithium., Results: A satisfactory response, defined as a fall by 40% or more in free thyroxine levels and clinical improvement, was achieved in eight patients within 1 to 2 weeks of lithium therapy. In four others, response occurred in 3 to 5 weeks. Response was slow and inadequate in one patient due to 'escape'. The median dosage of lithium was 750 mg daily, with a range of 500 to 1500 mg daily. The median serum lithium level was 0.63 mmol/L. Lithium toxicity was observed in one patient., Conclusions: A relatively low dose of lithium offers a safe and effective alternative means of controlling thyrotoxicosis in patients who cannot tolerate or do not respond to thionamides.

Objective: To assess the clinical utility and safety of the low-dose corticotropin stimulation test in the diagnosis of secondary adrenocortical insufficiency., Design: Prospective study., Setting: Regional hospital, Hong Kong., Participants: Seventy-two Chinese patients with suspected secondary adrenocortical insufficiency., Main Outcome Measure: Serum cortisol response during the low-dose corticotropin stimulation test, using the insulin tolerance test as the gold standard., Results: The 30-minute cortisol level during the low-dose corticotropin stimulation test was most closely correlated (r=0.79) with the peak cortisol level achieved during the insulin tolerance test. The optimum sensitivity and specificity of the low-dose corticotropin stimulation test were obtained at a cut-off value of 550 nmol/L or more for the 30-minute cortisol level. Using the insulin tolerance test as the gold standard for comparison, the low-dose corticotropin stimulation test had a sensitivity of 97%, a specificity of 78%, a positive predictive value of 81%, and a negative predictive value of 97% at this cut-off value. The positive likelihood ratio was 4.4 and the negative likelihood ratio 0.04., Conclusion: The low-dose corticotropin stimulation test, using the cortisol response at 30 minutes after synacthen 1 microg is a safe, convenient, and sensitive method for screening abnormalities of the hypothalamic-pituitary-adrenocortical axis in Chinese patients suspected of having secondary adrenocortical insufficiency.