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Most common methods of cellular analysis employ the top-down approach (investigating proteomics or genomics directly), thereby destroying the cell, which does not allow the possibility of using the same cell to correlate genomics with functional assays. Herein we describe an approach for single-cell tools that serve as a bottom-up approach. Our technology allows functional phenotyping to be conducted by observing the cytotoxicity of cells and then probe the underlying biology. We have developed a droplet microfluidic device capable of trapping droplets in the array and releasing the droplet of interest selectively using microvalves. Each droplet in the array encapsulates natural killer cells (NK cells) and tumour cells for real-time monitoring of burst kinetics and spatial coordination during killing by single NK cells. Finally, we use the microvalve actuation to selectively release droplets with the desired functional phenotype such as for fast and serial killing of target tumour cells by NK cells. From this perspective, our device allows for investigating first interactions and real-time monitoring of kinetics and later cell recovery on demand for single-cell omic analysis such as single-cell RNA sequencing (scRNA), which to date, is primarily based on in-depth analyses of the entire transcriptome of a relatively low number of cells.

Helicobacter pylori (H. pylori) increases production of reactive oxygen species (ROS) and activates signaling pathways associated with gastric cell invasion, which are mediated by matrix metalloproteinases (MMPs). We previously demonstrated that H. pylori activated mitogen-activated protein kinase (MAPK) and increased expression of MMP-10 in gastric epithelial cells. MMPs degrade the extracellular matrix, enhancing tumor invasion and cancer progression. The signaling pathway of phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is associated with MMP expression. ROS activates PIK3/AKT/mTOR signaling in cancer. Astaxanthin, a xanthophyll carotenoid, shows antioxidant activity by reducing ROS levels in gastric epithelial cells infected with H. pylori . This study aimed to determine whether astaxanthin inhibits MMP expression, cell invasion, and migration by reducing the PI3K/AKT/mTOR signaling in H. pylori -infected gastric epithelial AGS cells. H. pylori induced PIK3/AKT/mTOR and NF-κB activation, decreased IκBα, and induced MMP (MMP-7 and -10) expression, the invasive phenotype, and migration in AGS cells. Astaxanthin suppressed these H. pylori -induced alterations in AGS cells. Specific inhibitors of PI3K, AKT, and mTOR reversed the H. pylori -stimulated NF-κB activation and decreased IκBα levels in the cells. In conclusion, astaxanthin suppressed MMP expression, cell invasion, and migration via inhibition of PI3K/AKT/mTOR/NF-κB signaling in H. pylori -stimulated gastric epithelial AGS cells.

With the increasing use of MRI in clinical practice, the need for MRI-guided intervention is also increasing. Indeterminate lesions identified on MRI without mammographic or sonographic correlates will need to be approached under MRI guidance. MRI-guided biopsy is a skill that can be acquired with proper training and guidance. These procedures have their own set of challenges and issues; some of them are specific to the patient habitus in this region. Adequate knowledge and understanding of the challenges can help the radiologist to be better equipped to face these issues and solve them promptly during the procedure, thus increasing the overall success rate of the procedure. Not much local data from Asian countries is available on this front. This paper aims to share common challenges one may face while performing MRI-guided biopsy and share some tips and tricks to address these problems. Hopefully, this will help the readers achieve a higher success rate for MRI-guided interventions in their clinical practice.

Albeit the biodiesel production from suspended microalgal system has gained immense interests in recent years, the domineering limitation of being economically infeasible has hindered this technology from partaking into a large-scale operation. To curtail this issue, attached growth system had been introduced by various studies; however, those were still unable to alleviate the socio-economic challenges faced in commercializing the microalgal biomass production. Thus, this study had developed a novel approach in cultivating-cum-harvesting attached Chlorella vulgaris sp. microalgae, whilst using solid organic waste of palm kernel expeller (PKE) as the supporting and alimentation material for microalgal biofilm formation. The effects of three variables, namely, PKE dosage, light intensity, and photoperiod, were initially modelled and later optimized using Response Surface Methodology tool. The derived statistical models could predict the growth performances of attached microalgal biomass and lipid productivity. The optimum growing condition was attained at PKE dosage of 5.67 g/L, light intensity of 197 μmol/m 2 s and photoperiod of 8 light and 16 dark hours/cycle, achieving the microalgal density and lipid content of 9.87 ± 0.05 g/g and 3.39 ± 0.28 g/g, respectively, with lipid productivity of 29.6 mg/L day. This optimum condition had led to the intensification of biodiesel quality with a high percentage of monounsaturated fatty acid, i.e., oleic acid (C18:1), encompassing 81.86% of total fatty acid methyl ester components. Given that the positive acquisition of PKE as an excellent supporting material in enhancing the microalgal density and lipid productivity that had resulted in the commercially viable biodiesel quality, this study served as a novel revolution in augmenting the microalgae and solid waste utilities for sustainable energy generation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and triggers various stomach diseases. H. pylori induces reactive oxygen species (ROS) production and DNA damage. The heterodimeric Ku70/Ku80 protein plays an essential role in the repair of DNA double-strand breaks (DSB). Oxidative stress stimulate apoptosis and DNA damage that can be repaired by Ku70/80. However, excessive reactive oxygen species (ROS) can cause Ku protein degradation, resulting in DNA fragmentation and apoptosis. α-lipoic acid (α-LA), which is found in organ meats such as liver and heart, spinach, broccoli, and potatoes, quenches free radicals, chelates metal ions, and reduces intracellular DNA damage induced by oxidative stress. Here, we investigated whether H. pylori decreases Ku70/80 and induces apoptosis, and whether α-LA inhibits changes induced by H. pylori . We analyzed ROS, DNA damage markers (γ-H2AX, DNA fragmentation), levels of Ku70/80, Ku-DNA binding activity, Ku80 ubiquitination, apoptosis indices (Bcl-2, Bax, apoptosis-inducing factor (AIF), and caspase-3), and viability in a human gastric epithelial adenocarcinoma cell line (AGS). H. pylori increased ROS, DNA damage markers, Ku80 ubiquitination, and consequently induced apoptosis. It also decreased nuclear Ku70/80 levels and Ku-DNA-binding activity; increased Bax expression, caspase-3 cleavage, and truncated AIF; but decreased Bcl-2 expression. These H. pylori -induced alterations were inhibited by α-LA. The antioxidant N-acetylcysteine and proteasome inhibitor MG-132 suppressed H. pylori -induced cell death and decreased nuclear Ku70/80 levels. The results show that oxidative stress induced Ku70/80 degradation via the ubiquitin-proteasome system, leading to its nuclear loss and apoptosis in H. pylori -infected cells. In conclusion, α-LA inhibited apoptosis induced by H. pylori by reducing ROS levels and suppressing the loss of Ku70/80 proteins in AGS cells.

Cerulein‑induced pancreatitis resembles human acute pancreatitis in terms of pathological events, such as enzymatic activation and inflammatory cell infiltration in the pancreas. Cerulein is a cholecystokinin analog that increases levels of reactive oxygen species (ROS) and interleukin‑6 (IL‑6) expression level in pancreatic acinar cells. Serum levels of resistin, which is secreted from adipocytes, are reportedly higher in patients with acute pancreatitis than in healthy individuals. Previously, it was shown that the adipokine resistin can aggravate the cerulein‑induced increase in ROS levels and IL‑6 expression level in pancreatic acinar cells. Peroxisome proliferator‑activated receptor‑gamma (PPAR‑γ) is a key regulator of the transcription and expression of antioxidant enzymes, including heme oxygenase 1 (HO‑1) and catalase. α‑lipoic acid, a naturally occurring dithiol antioxidant, can prevent cerulein‑induced pancreatic damage in rats. In the present study, it was aimed to investigate whether α‑lipoic acid can attenuate the cerulein/resistin‑induced increase in IL‑6 expression and ROS levels via PPAR‑γ activation in pancreatic acinar AR42J cells. The anti‑inflammatory mechanism of α‑lipoic acid was determined using reverse transcription‑quantitative PCR, western blot analysis, enzyme‑linked immunosorbent assay, immunofluorescence staining and fluorometry. Treatment with cerulein and resistin increased ROS levels and IL‑6 expression level, which were inhibited by α‑lipoic acid in pancreatic acinar cells. α‑lipoic acid increased the nuclear translocation and expression level of PPAR‑γ and the expression levels of its target genes: HO‑1 and catalase. The PPAR‑γ antagonist GW9662 and HO‑1 inhibitor zinc protoporphyrin reversed the inhibitory effect of α‑lipoic acid on cerulein/resistin‑induced increase in ROS and IL‑6 levels. In conclusion, α‑lipoic acid inhibits the cerulein/resistin‑induced increase in ROS production and IL‑6 expression levels by activating PPAR‑γ and inducing the expression of HO‑1 and catalase in pancreatic acinar cells.

The low therapeutic efficacy of conventional cancer chemotherapy has been associated with an immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs), which display an M2-like phenotype, are abundant in many tumors and facilitate tumor growth and resistance to therapy. Here, we show that poly(L-arginine) (PLR), a cationic poly(amino acid) can induce the polarization of macrophages into the tumor-suppressive M1 phenotype, in vitro . Further, we demonstrate that hyaluronic acid (HA) and PLR-coated manganese dioxide (MnO 2 ) nanoparticles (hpMNPs) display efficient anti-cancer effects by upregulating nitric oxide (NO) production. Surface modification with biocompatible HA reduced the cytotoxicity of the cationic PLR. Additionally, manganese ions released from these nanoparticles by the high concentrations of glutathione (GSH) in the TME increased iNOS expression level in macrophages and enhanced the performance of T 1 weighted magnetic resonance imaging. Particularly, our results illustrate the therapeutic effects, such as growth inhibition and apoptosis of tumor cells, of hpMNP treated macrophages. Therefore, the newly designed multifunctional PLR-assisted MNPs may facilitate the polarization of M2 macrophages into the M1 phenotype, which can mediate NO-dependent anticancer immunotherapy.

Background: At the workplace, health care workers face multiple challenges in maintaining healthy dietary behaviors, which is the major factor behind obesity. A hospital-wide mass health screening exercise showed an increasing trend in the prevalence of obesity and median BMI from 2004 to 2019, as well as a higher crude obesity rate among shift workers., Objective: We aimed to evaluate the effectiveness of mobile app-based health coaching and incentives for achieving weight loss from better dietary choices among hospital nurses., Methods: We conducted a pilot study from June 2019 to March 2020, involving the use of a health-coaching app by 145 hospital nurses over 6 months. Weight and BMI were self-reported, and food scores were calculated. Data among overweight nurses, shift work nurses, and incentive groups were analyzed., Results: A total of 61 nurses were included in the final analysis. Of these 61 nurses, 38 (62%) lost weight. The median percentage weight loss was 1.2% (IQR 0%-2.9%; P<.001), and the median decrease in BMI was 0.35 (IQR -0.15 to 0.82; P<.001), but they were not clinically significant. The median improvement in the food score was 0.4 (IQR 0-0.8). There was no difference between the incentive and nonincentive groups. A total of 49 (34%) participants engaged for ≥8 weeks., Conclusions: The study demonstrated an association between the use of app-based health coaching and the attainment of some weight loss in nurses, without a significant improvement in the food score. Incentives may nudge on-boarding, but do not sustain engagement., (©Wei Xiang Lim, Stephanie Fook-Chong, John Wah Lim, Wee Hoe Gan. Originally published in JMIR Nursing (https://nursing.jmir.org), 15.07.2022.)

Black soldier fly larvae (BSFL) have been deployed to valorize various organic wastes. Nonetheless, its growth rate whilst being offered with waste activated sludge (WAS) is not promising, likely by virtue of the presence of extracellular polymeric substances' structure in WAS. In this work, the WAS were first thermally pre-treated under different treatment temperatures and durations before being administered as the feeding substrates for BSFL. The results showed the thermal pre-treatment could improve WAS palatability and subsequently, enhance the growth of BSFL especially after the pre-treatments at 75 °C and above. The highest larva weight gained was recorded at 2.16 mg/larva for the WAS sample being pre-treated at 90 °C and 16 h. Furthermore, the samples pre-treated above 75 °C also achieved higher degradation rates, indicating that the 75 °C was a threshold temperature to effectively hydrolyze the WAS. The changes of WAS characteristics, namely, (i) soluble chemical oxygen demand (SCOD), (ii) soluble carbohydrate, (iii) soluble protein, (iv) humic substances and (v) total soluble protein and humic substances, after the thermal pre-treatments were also studied in correlating with the BSFL growth. Accordingly, a model was successfully developed with the highest R 2 value attained at 0.95, evidencing the SCOD was the most suitable WAS characteristic to accurately predict the BSFL growth behavior., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to examine the advantages and usefulness of transient elastography (Fibroscan ® ) in diagnosing non-alcoholic steatohepatitis in children and adolescents compared to those of abdominal computed tomography and liver ultrasonography., Methods: Forty-six children and adolescent participants aged between 6 and 16 years who underwent transient elastography (Fibroscan ® ) as well as liver ultrasonography or abdominal computed tomography were included. Thirty-nine participants underwent liver ultrasonography and 11 underwent computed tomography. The physical measurements, blood test results, presence of metabolic syndrome, and the degree of liver steatosis and liver fibrosis were analyzed, and their correlations with transient elastography (Fibroscan ® ), abdominal computed tomography, and liver ultrasonography, as well as the correlations between examinations, were analyzed., Results: Thirty-six participants (78.3%) were boys, and the mean age was 12.29±2.57 years, with a mean body mass index of 27.88±4.28. In the 46 participants, the mean values for aspartate aminotransferase, alanine aminotransferase, and total bilirubin were 89.87±118.69 IU/L, 138.54±141.79 IU/L, and 0.77±0.61 mg/dL, respectively. Although transient elastography (Fibroscan ® ) and abdominal computed tomography grading had a statistically significant positive correlation with aspartate aminotransferase and alanine aminotransferase values, the correlations between the results of grading performed by transient elastography (Fibroscan ® ), abdominal computed tomography, and liver ultrasonography were not statistically., Conclusion: We confirmed that each examination was correlated with the results of some blood tests, suggesting the usefulness and possibility of diagnosis and treatment of steatohepatitis mediated by transient elastography (Fibroscan ® ) in the department of pediatrics., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest., (Copyright © 2022 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

The unique physicochemical and localized surface plasmon resonance assets of gold nanorods (GNRs) have offered combined cancer treatments with real-time diagnosis by integrating diverse theragnostic modalities into a single nanoplatform. In this work, a unique multifunctional nanohybrid material based on GNRs was designed for in vitro and in vivo tumor imaging along with synergistic and combinatorial therapy of tumor. The hybrid material with size less than 100 nm was achieved by embedding indocyanine green (ICG) on mesoporous silica-coated GNRs with further wrapping of reduced graphene oxide (rGO) and then attached with doxorubicin (DOX) and polyethylene glycol. The nanohybrid unveiled noteworthy stability and competently protected the embedded ICG from further aggregation, photobleaching, and nucleophilic attack by encapsulation of GNRs-ICG with rGO. Such combination of GNRs-ICG with rGO and DOX served as a real-time near-infrared (NIR) contrast imaging agent for cancer diagnosis. The hybrid material exhibits high NIR absorption property along with three destined capabilities, such as, nanozymatic activity, photothermal activity, and an excellent drug carrier for drug delivery. The integrated properties of the nanohybrid were then utilized for the triple mode of combined therapeutics of tumor cells, through synergistic catalytic therapy and chemotherapy with combinatorial photothermal therapy to achieve the maximum cancer killing efficiency. It is assumed that the assimilated multimodal imaging and therapeutic capability in single nanoparticle platform is advantageous for future practical applications in cancer diagnosis, therapy, and molecular imaging., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Low temperature thermal pre-treatment is a low-cost method to break down the structure of extracellular polymeric substances in waste activated sludge (WAS) while improving the sludge biodegradability. However, previous models on low temperature thermal pre-treatment did not adequately elucidate the behaviour of sludge hydrolysis process for the duration ranging from 5 to 9 h. Therefore, this work had developed an inclusive functional model to describe the kinetics of sludge hydrolysis for a wide range of treatment conditions (30 °C-90 °C within 0 and 16 h). As compared with treatment duration, the treatment temperature played a greater impact in solubilizing WAS. Accordingly, the 90 °C treatment had consistently produced WAS with the highest degree of solubility. Nonetheless, the mediocre discrepancies between 90 °C and 75 °C may challenge the practicality of increasing the treatment temperatures beyond 75 °C. The effects of treatment duration on soluble chemical oxygen demand, soluble carbohydrate and soluble protein were only significant during the first 4 h, except for humic substances release that continued to increase with treatment duration. Finally, a good fit with R 2  > 0.95 was achieved using an inclusive multivariate non-linear model, substantiating the functionality to predict the kinetics of sludge hydrolysis at arbitrary treatment conditions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Theoretical predictions of carbon dioxide absorption flux were analyzed by developing one-dimensional mathematical modeling using the chemical absorption theory based on mass-transfer resistances in series. The CO 2 absorption into monoethanolamine (MEA) solutions was treated as chemical absorption, accompanied by a large equilibrium constant. The experimental work of the CO 2 absorption flux using MEA solution was conducted in double-unit flat-plate membrane contactors with embedded 3D turbulence promoters under various absorbent flow rates, CO 2 feed flow rates, and inlet CO 2 concentrations in the gas feed stream for both concurrent and countercurrent flow operations. A more compact double-unit module with embedded 3D turbulence promoters could increase the membrane stability to prevent flow-induced vibration and enhance the CO 2 absorption rate by overwhelming the concentration polarization on the membrane surfaces. The measured absorption fluxes with a near pseudo-first-order reaction were in good agreement with the theoretical predictions for the CO 2 absorption efficiency in aqueous MEA solutions, which was shown to be substantially larger than the physical absorption in water. By embedding 3D turbulence promoters in the MEA feed channel, the new design accomplishes a considerable CO 2 absorption flux compared with an empty channel as well as the single unit module. This demonstrates the value and originality of the present study regarding the technical feasibility. The absorption flux enhancement for the double-unit module with embedded 3D turbulence promoters could provide a maximum relative increase of up to 40% due to the diminution in the concentration polarization effect. The correlated equation of the average Sherwood number was obtained numerically using the fourth Runge-Kutta method in a generalized and simplified expression to calculate the mass transfer coefficient of the CO 2 absorption in the double-unit flat-plate membrane contactor with turbulence promoter channels.

Being the second-largest country in the production of palm oil, Malaysia has a massive amount of palm kernel expeller (PKE) leftover. For that purpose, black soldier fly larvae (BSFL) are thus employed in this study to valorize the PKE waste. More specifically, this work elucidated the effects of the pre-fermentation of PKE via different amounts of Rhizopus oligosporus to enhance PKE palatability for the feeding of BSFL. The results showed that fermentation successfully enriched the raw PKE and thus contributed to the better growth of BSFL. BSFL grew to be 34% heavier at the optimum inoculum volume of 0.5 mL/10 g dry weight of PKE as compared to the control. Meanwhile, excessive fungal inoculum induced competition between BSFL and R. oligosporus , resulting in a reduction in BSFL weight. Under optimum feeding conditions, BSFL also registered the highest lipid yield (24.7%) and protein yield (44.5%). The biodiesel derived from BSFL lipid had also shown good compliance with the European biodiesel standard EN 14214. The high saturated fatty acid methyl esters (FAMEs) content (C12:0, C14:0, C16:0) in derived biodiesel made it highly oxidatively stable. Lastly, the superior degradation rate of PKE executed by BSFL further underpinned the sustainable conversion process in attaining valuable larval bioproducts.

In alcoholic pancreatitis, alcohol increases gut permeability, which increases the penetration of endotoxins, such as lipopolysaccharides (LPS). LPS act as clinically significant triggers to increase pancreatic damage in alcoholic pancreatitis. Ethanol or LPS treatment increases reactive oxygen species (ROS) production in pancreatic acinar cells. ROS induce inflammatory cytokine production in pancreatic acinar cells, leading to pancreatic inflammation. The nuclear erythroid-2-related factor 2 (Nrf2) pathway is activated as a cytoprotective response to oxidative stress, and induces the expression of NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Lycopene exerts anti-inflammatory and antioxidant effects in various cells. We previously showed that lycopene inhibits NADPH oxidase to reduce ROS and IL-6 levels, and zymogene activation in ethanol or palmitoleic acid-treated pancreatic acinar cells. In this study, we examined whether lycopene inhibits IL-6 expression by activating the Nrf2/NQO1-HO-1 pathway, and reducing intracellular and mitochondrial ROS levels, in ethanol and LPS-treated pancreatic AR42J cells. Lycopene increased the phosphorylated and nuclear-translocated Nrf2 levels by decreasing the amount of Nrf2 sequestered in the cytoplasm via a complex formation with Kelch-like ECH1-associated protein 1 (Keap1). Using exogenous inhibitors targeting Nrf2 and HO-1, we showed that the upregulation of activated Nrf2 and HO-1 results in lycopene-induced suppression of IL-6 expression and ROS production. The consumption of lycopene-rich foods may prevent the development of ethanol and LPS-associated pancreatic inflammation by activating Nrf2-mediated expression of NQO1 and HO-1, thereby decreasing ROS-mediated IL-6 expression in pancreatic acinar cells.

Helicobacter pylori ( H. pylori ) causes gastric diseases by increasing reactive oxygen species (ROS) and interleukin (IL)-8 expression in gastric epithelial cells. ROS and inflammatory responses are regulated by the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of Nrf2 target genes, superoxide dismutase ( SOD ) and heme oxygenase-1 ( HO-1 ). We previously demonstrated that Korean red ginseng extract (RGE) decreases H. pylori -induced increases in ROS and monocyte chemoattractant protein 1 in gastric epithelial cells. We determined whether RGE suppresses the expression of IL-8 via Nrf2 activation and the expression of SOD and HO-1 in H. pylori -infected gastric epithelial AGS cells. H. pylori -infected cells were treated with RGE with or without ML385, an Nrf2 inhibitor, or zinc protoporphyrin (ZnPP), a HO-1 inhibitor. Levels of ROS and IL-8 expression; abundance of Keap1, HO-1, and SOD; levels of total, nuclear, and phosphorylated Nrf2; indices of mitochondrial dysfunction (reduction in mitochondrial membrane potential and ATP level); and SOD activity were determined. As a result, RGE disturbed Nrf2-Keap1 interactions and increased nuclear Nrf2 levels in uninfected cells. H. pylori infection decreased the protein levels of SOD-1 and HO-1, as well as SOD activity, which was reversed by RGE treatment. RGE reduced H. pylori -induced increases in ROS and IL-8 levels as well as mitochondrial dysfunction. ML385 or ZnPP reversed the inhibitory effect of RGE on the alterations caused by H. pylori . In conclusion, RGE suppressed IL-8 expression and mitochondrial dysfunction via Nrf2 activation, induction of SOD-1 and HO-1, and reduction of ROS in H. pylori -infected cells.

Background: Fear of cancer recurrence (FCR) has been addressed as a cause of emotional distress among breast cancer survivors (BCSs). This study aimed to systematically review the evidence on randomized controlled trials (RCTs) of cognitive behavioral therapy (CBT) designed to reduce FCR among BCSs., Methods: A systematic review of published original research articles meeting the inclusion criteria was conducted. Five electronic databases, including the Cochrane Library, CINAHL, PubMed, PsycINFO, and Web of Science, were independently searched to identify relevant articles. The Consolidated Standards of Reporting Trials (CONSORT) 2010 checklist was used to evaluate the quality of the eligible studies., Results: Through a database search and a manual review process, seventeen quantitative studies with an RCT study design were included in the current systematic review. The interventions varied greatly in length and intensity, but the study designs and methodologies were similar. RCTs with face-to-face interventions of at least 1 month seemed to be more effective in reducing FCR outcomes and complying with than the CONSORT 2010 criteria than those with a brief online or telephone format of interventions; nevertheless, most RCT interventions appeared to be effective., Conclusions: These findings highlight the importance of conducting well-designed CBT interventions to reduce FCR in BCSs with diverse populations at multiple sites, thereby improving the quality of research in this area., (© 2021. The Author(s).)

The high investment cost required by modern treatment technologies of hazardous sewage sludge such as incineration and anaerobic digestion have discouraged their application by many developing countries. Hence, this review elucidates the status, performances and limitations of two low-cost methods for biological treatment of hazardous sewage sludge, employing vermicomposting and black soldier fly larvae (BSFL). Their performances in terms of carbon recovery, nitrogen recovery, mass reduction, pathogen destruction and heavy metal stabilization were assessed alongside with the mature anaerobic digestion method. It was revealed that vermicomposting and BSFL were on par with anaerobic digestion for carbon recovery, nitrogen recovery and mass reduction. Thermophilic anaerobic digestion was found superior in pathogen destruction because of its high operational temperature. Anaerobic digestion also had proven its ability to stabilize heavy metals, but no conclusive finding could confirm similar application from vermicomposting or BSFL treatment. However, the addition of co-substrates or biochar during vermicomposting or BSFL treatment may show synergistic effects in stabilizing heavy metals as demonstrated by anaerobic digestion. Moreover, vermicomposting and BSFL valorization had manifested their potentialities as the low-cost alternatives for treating hazardous sewage sludge, whilst producing value-added feedstock for biochemical industries., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The near-perivascular accumulation in solid tumors and short-lived span in circulation, derails even the most competent nanoparticles (NPs) from achieving their maximum therapeutic potential. Moreover, delivering them across the blood brain/tumor barrier (BBB/BTB) is further challenging to sought anticancer effect. To address these key challenges, we designed a linearly aligned nucleic acid-complexed polydixylitol-based polymeric nanochains (X-NCs), with inherent hyperosmotic properties enabling transmigration of the BBB/BTB and navigation through deeper regions of the brain tumor. The high aspect ratio adds shape-dependent functional aspects to parent particles by providing effective payload increment and nuclear factor of activated T cells-5 (NFAT5)-mediated cellular uptake. Therefore, serine hydroxymethyltransferase 1 (SHMT1) siRNA-loaded nanochains not only demonstrated to transmigrate the BTB, but also resulted in remarkably reducing the tumor size to 97% in the glioblastoma xenograft brain tumor mouse models. Our study illustrates how the hyperosmotic nanochains with high aspect ratio and aligned structure can accelerate a therapeutic effect in aggressive brain tumors post-transmigration of the BBB/BTB by utilizing an NFAT5 mode of uptake mechanism., (Copyright © 2021. Published by Elsevier Ltd.)

The presence of conventional and emerging pollutants infiltrating into our water bodies is a course of concern as they have seriously threatened water security. Established techniques such as photocatalysis and membrane technology have proven to be promising in removing various persistent organic pollutants (POP) from wastewaters. The emergence of hybrid photocatalytic membrane which incorporates both photocatalysis and membrane technology has shown greater potential in treating POP laden wastewater based on their synergistic effects. This article provides an in-depth review on the roles of both photocatalysis and membrane technology in hybrid photocatalytic membranes for the treatment of POP containing wastewaters. A concise introduction on POP's in terms of examples, their origins and their effect on a multitude of organisms are critically reviewed. The fundamentals of photocatalytic mechanism, current directions in photocatalyst design and their employment to treat POP's are also discussed. Finally, the challenges and future direction in this field are presented., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The cellular components of Akkermansia muciniphila are considered potential biotherapeutics for the improvement of obesity, diabetes, and metabolic diseases. However, the molecular-based mechanism of A. muciniphila for treatment of obesity, which can provide important evidence for human research, has rarely been explored. Here, we applied integrative multiomics approaches to investigate the underlying molecular mechanism involved in obesity treatment by A. muciniphila. First, the treatment with a cell lysate of A. muciniphila reduced lipid accumulation in 3T3-L1 cells and downregulated the mRNA expression of proteins involved in adipogenesis and lipogenesis. Our proteomic results revealed that A. muciniphila decreased the expression of proteins involved in fat cell differentiation, fatty acid metabolism, and energy metabolism in adipocytes. Moreover, A. muciniphila significantly reduced the level of metabolites related to glycolysis, the TCA cycle, and ATP in adipocytes. Interestingly, serine protease inhibitor A3 (SERPINA3) homologs were overexpressed in the 3T3-L1 cells treated with A. muciniphila. Small interfering RNA (siRNA) transfection demonstrated that A. muciniphila upregulates SERPINA3G expression and inhibits lipogenesis in adipocytes. Taken together, our multiomics-based approaches enabled to uncover the molecular mechanism of A. muciniphila for treatment of obesity and provide potent anti-lipogenic agents., (© 2021 Wiley-VCH GmbH.)

Quantitative mapping of temperature fields with nanometric resolution is critical in various areas of scientific research and emerging technology, such as nanoelectronics, surface chemistry, plasmonic devices, and quantum systems. A key challenge in achieving quantitative thermal imaging with scanning thermal microscopy (SThM) is the lack of knowledge of the tip-sample thermal resistance ( R TS ), which varies with local topography and is critical for quantifying the sample temperature. Recent advances in SThM have enabled simultaneous quantification of R TS and topography in situations where the temperature field is modulated enabling quantitative thermometry even when topographical features cause significant variations in R TS . However, such an approach is not applicable to situations where the temperature modulation of the device is not readily possible. Here we show, using custom-fabricated scanning thermal probes (STPs) with a sharp tip (radius ∼25 nm) and an integrated heater/thermometer, that one can quantitatively map unmodulated temperature fields, in a single scan, with ∼7 nm spatial resolution and ∼50 mK temperature resolution in a bandwidth of 1 Hz. This is accomplished by introducing a modulated heat input to the STP and measuring the AC and DC responses of the probe's temperature which allow for simultaneous mapping of the tip-sample thermal resistance and sample surface temperature. The approach presented here─contact resistance resolved scanning thermal microscopy (CR-SThM)─can greatly facilitate temperature mapping of a variety of microdevices under practical operating conditions.

In the present paper, low-dimensional Ag 2 S QDs were fabricated for the first time, with four different dithiocarbazate derivative Schiff bases (SB) as capping agents in a one-pot synthesis. These SB-capped Ag 2 S QDs were almost spherical with an average size range of 4.0 to 5.6 nm, which is slightly smaller than conventional thioglycolic acid (TGA)-capped Ag 2 S QDs. We demonstrate that the growth of Gram-positive bacteria ( Bacillus subtillus and Staphylococcus aureus ), Gram-negative bacteria ( Escherichia coli and Pseudomonas aeruginosa ), and a prevalent fungal pathogen ( Candida albicans ) are inhibited more when the bacterial and fungal cells were nurtured with the synthesized SB-Ag 2 S QDs, compared with TGA-Ag 2 S QDs or free unbound Schiff bases. The minimum inhibitory concentration (MIC) results confirmed that even low concentrations of SB-Ag 2 S QDs were able to inhibit bacterial (MIC 5-75 μg mL -1 ) and fungal growth (MIC 80-310 μg mL -1 ), and in some cases they performed better than streptomycin (8-25 μg mL -1 ). Lethality bioassay results confirmed that SB-Ag 2 S QDs were not toxic to brine shrimp ( Artemia salina ). The results show that capping agents are essential in the design of functional Ag 2 S QDs, and highlight that Schiff bases provide an excellent opportunity to optimize the biological activities of silver based QDs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The aim of this study was to develop a green method to fabricate a novel CS modified N-(4-hydroxyphenyl)- methacrylamide conjugate (CSNHMA) and to evaluate its biomedical potential. CSNHMA has been prepared by a simple method via aza Michael addition reaction between CS and N- (4-hydroxyphenyl)-methacrylamide (NHMA) in ethanol. Its structural and morphological properties were characterized by various analysis techniques. The obtained results confirmed that a highly porous network structure of CSNHMA was successfully synthesized via aza Michael addition reaction. Consequently, it was analyzed as a drug and gene carrier. CSNHMA/pGL3 showed an enhanced buffering capacity due to the presence of NHMA moiety leading to higher transfection efficiency in all cancer cells (A549, HeLa and HepG2) as compared to native CS and Lipofectamine®. Therefore, these findings clearly support the possibility of using CSNHMA as a good transfection agent. For in vitro drug release study, we prepared CSNHMA nanoparticles (NPs) and curcumin loaded CSNHMA NPs of size <230 nm respectively via the non-toxic ionic gelation route and the encapsulation efficiency of drug was found to be 77.03%. In vitro drug release studies demonstrated a faster and sustained release of curcumin loaded CSNHMA NPs at pH 5.0 compared to physiological pH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

To suffice the escalating global energy demand, microalgae are deemed as high potential surrogate feedstocks for liquid fuels. The major encumbrance for the commercialization of microalgae cultivation is due to the high costs of nutrients such as carbon, phosphorous, and nitrogen. Meanwhile, the organic-rich anaerobic digestate which is difficult to be purified by conventional techniques is appropriate to be used as a low-cost nutrient source for the economic viability and sustainability of microalgae production. This option is also beneficial in terms of reutilize the organic fraction of solid waste instead of discarded as zero-value waste. Anaerobic digestate is the side product of biogas production during anaerobic digestion process, where optimum nutrients are needed to satisfy the physiological needs to grow microalgae. Besides, the turbidity, competing biological contaminants, ammonia and metal toxicity of the digestate are also potentially contributing to the inhibition of microalgae growth. Thus, this review is aimed to explicate the feasibility of utilizing the anaerobic digestate to cultivate microalgae by evaluating their potential challenges and solutions. The proposed potential solutions (digestate dilution and pre-treatment, microalgae strain selection, extra organics addition, nitrification and desulfurization) corresponding to the state-of-the-art challenges are applicable as future directions of the research., 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 © 2021 Elsevier B.V. All rights reserved.)

This study aimed to develop a label-free fluorescent aptasensor for the detection of diazinon (DZN) on a cyclic olefin copolymer (COC) substrate. The aptasensor design was based on rolling circle amplification (RCA) technology and the use of self-assembled copper nanoparticles (CuNPs). A dual-function (DF) probe, capable of binding to circular DNA and an aptamer, was designed and immobilized on a COC-bottom 96-well plate. An aptamer was used for selective recognition of DZN, and the specific site of the aptamer that strongly reacted with DZN was successfully identified using circular dichroism (CD) analysis. In presence of DZN, the aptamer and DZN formed a strong complex, thus providing an opportunity for hybridization of the DF probe and circular DNA, thereby initiating an RCA reaction. Repetitive poly thymine (T) sequence with a length of 30-mer, generated in the RCA reaction, served as a template for the synthesis of fluorescent copper nanoparticles, emitting an orange fluorescence signal (at approximately 620 nm) proportional to the amount of RCA product, within 10 min under UV irradiation. The CuNP fluorescence was imaged and quantified using an image analysis software. A linear correlation of the fluorescence signal was confirmed in the DZN concentration range of 0.1-3 ppm, with a detection limit of 0.15 ppm. Adoption of a label-free detection method, utilizing RCA and fluorescent CuNPs on COC substrates, reduced the need for complex equipment and requirements for DZN analysis, thereby representing a simple and rapid sensing method circumventing the limitations of current complex and labor-intensive methods., Electronic Supplementary Material Esm: The online version of this article (doi:10.1007/s12257-021-0220-0) contains supplementary material, which is available to authorized users., (© The Korean Society for Biotechnology and Bioengineering and Springer 2022.)

Despite the expanding clinical application of hydroxychloroquine in dermatology, the overall data on hydroxychloroquine use among dermatologists are limited. With retrospective review of the medical records of the 790 patients who were prescribed hydroxychloroquine, we classified the diagnoses into 12 disease categories, the lupus erythematosus group being the largest. The lupus erythematosus group had the longest prescription duration (median, 6.2 months), whereas the photodermatitis group had a significantly shorter prescription duration (median, 0.5 months). The overall good response rate was 77.1%. The photodermatitis group had the best response (88.7%), followed by the lupus panniculitis (85.1%) and lichen planus (84.4%). In conclusion, hydroxychloroquine has proven utility for various inflammatory skin diseases, including but not limited to cutaneous lupus erythematosus., (© 2021 Japanese Dermatological Association.)

A recurrent pandemic with unpredictable viral nature has implied the need for a rapid diagnostic technology to facilitate timely and appropriate countermeasures against viral infections. In this study, conductive polymer-based nanoparticles have been developed as a tool for rapid diagnosis of influenza A (H1N1) virus. The distinctive property of a conductive polymer that transduces stimulus to respond, enabled immediate optical signal processing for the specific recognition of H1N1 virus. Conductive poly(aniline-co-pyrrole)-encapsulated polymeric vesicles, functionalized with peptides, were fabricated for the specific recognition of H1N1 virus. The low solubility of conductive polymers was successfully improved by employing vesicles consisting of amphiphilic copolymers, facilitating the viral titer-dependent production of the optical response. The optical response of the detection system to the binding event with H1N1, a mechanical stimulation, was extensively analyzed and provided concordant information on viral titers of H1N1 virus in 15 min. The specificity toward the H1N1 virus was experimentally demonstrated via a negative optical response against the control group, H3N2. Therefore, the designed system that transduces the optical response to the target-specific binding can be a rapid tool for the diagnosis of H1N1., Electronic Supplementary Material: Supplementary material (Table S1 and Figs. S1-S8) is available in the online version of this article at 10.1007/s12274-021-3772-6., (© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021.)

BiFeO 3 nanoparticle decorated on flower-like ZnO (BiFeO 3 /ZnO) was fabricated through a facile hydrothermal-reflux combined method. This material was utilized as a composite photocathode for the first time in microbial fuel cell (MFC) to reduce the copper ion (Cu 2+ ) and power generation concomitantly. The resultant BiFeO 3 /ZnO-based MFC displayed distinct photoelectrocatalytic activities when different weight percentages (wt%) BiFeO 3 were used. The 3 wt% BiFeO 3 /ZnO MFC achieved the maximum power density of 1.301 W m -2 in the catholyte contained 200 mg L -1 of Cu 2+ and the power density was greatly higher than those pure ZnO and pure BiFeO 3 photocathodes. Meanwhile, the MFC exhibited 90.7% removal of Cu 2+ within 6 h under sunlight exposure at catholyte pH 4. The addition of BiFeO 3 nanoparticles not only manifested outstanding capability in harvesting visible light, but also facilitated the formation of Z-scheme BiFeO 3 /ZnO heterojunction structure to induce the charge carrier transfer along with enhanced redox abilities for the cathodic reduction. The pronounced electrical output and Cu 2+ reduction efficiencies can be realized through the synergistic cooperation between the bioanode and BiFeO 3 /ZnO photocathode in the MFC. Furthermore, the developed BiFeO 3 /ZnO composite presented a good stability and reusability of photoelectrocatalytic activity up to five cyclic runs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Over the past decade, there has been a surge of interest in using char (hydrochar or biochar) derived from biomass as persulfate (PS, either peroxymonosulfate or peroxydisulfate) activator for anthropogenic pollutants removal. While extensive investigation showed that char could be used as a PS activator, its sustainability over prolonged application is equivocal. This review provides an assessment of the knowledge gap related to the sustainability of char as a PS activator. The desirable char properties for PS activation are identified, include the high specific surface area and favorable surface chemistry. Various synthesis strategies to obtain the desirable properties during biomass pre-treatment, hydrochar and biochar synthesis, and char post-treatment are discussed. Thereafter, factors related to the sustainability of employing char as a PS activator for anthropogenic pollutants removal are critically evaluated. Among the critical factors include performance uncertainty, competing adsorption process, char stability during PS activation, biomass precursor variation, scalability, and toxic components in char. Finally, some potential research directions are provided. Fulfilling the sustainability factors will provide opportunity to employ char as an economical and efficient catalyst for sustainable environmental remediation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Endophytic fungi are microorganisms that colonize living plants' tissues without causing any harm. They are known as a natural source of bioactive metabolites with diverse pharmacological functions. Many structurally different chemical metabolites were isolated from endophytic fungi. Recently, the increasing trends in human health problems and diseases have escalated the search for bioactive metabolites from endophytic fungi. The conventional bioassay-guided study is known as laborious due to chemical complexity. Thus, metabolomics studies have attracted extensive research interest owing to their potential in dealing with a vast number of metabolites. Metabolomics coupled with advanced analytical tools provides a comprehensive insight into systems biology. Despite its wide scientific attention, endophytic fungi metabolomics are relatively unexploited. This review highlights the recent developments in metabolomics studies of endophytic fungi in obtaining the global metabolites picture.

While two-dimensional (2D) hexagonal boron nitride (h-BN) is emerging as an atomically thin and dangling bond-free insulating layer for next-generation electronics and optoelectronics, its practical implementation into miniaturized integrated circuits has been significantly limited due to difficulties in large-scale growth directly on epitaxial semiconductor wafers. Herein, the realization of a wafer-scale h-BN van der Waals heterostructure with a 2 in. AlGaN/GaN high-electron mobility transistor (HEMT) wafer using metal-organic chemical vapor deposition is presented. The combination of state-of-the-art microscopic and spectroscopic analyses and theoretical calculations reveals that the heterointerface between ∼2.5 nm-thick h-BN and AlGaN layers is atomically sharp and exhibits a very weak van der Waals interaction without formation of a ternary or quaternary alloy that can induce undesired degradation of device performance. The fabricated AlGaN/GaN HEMT with h-BN shows very promising performance including a cutoff frequency ( f T ) and maximum oscillation frequency ( f MAX ) as high as 28 and 88 GHz, respectively, enabled by an effective passivation of surface defects on the HEMT wafer to deliver accurate information with minimized power loss. These findings pave the way for practical implementation of 2D materials integrated with conventional microelectronic devices and the realization of future all-2D electronics.

Streptococcus zoonotic bacteria cause serious problems in aquaculture with clinical effects on humans. A structure-antibacterial activity relationships analysis of 22 isoflavones isolated from M. tricuspidata (leaves, ripe fruits, and unripe fruits) against S. iniae revealed that prenylation of the isoflavone skeleton was an important key for their antibacterial activities (minimum inhibitory concentrations: 1.95-500 μg/mL). Through principal component analysis, characteristic prenylated isoflavones such as 6,8-diprenlygenistein ( 4 ) were identified as pivotal compounds that largely determine each part's antibacterial activities. M. tiricuspidata ripe fruits (MTF), which showed the highest antibacterial activity among the parts tested, were optimized for high antibacterial activity and low cytotoxicity on fathead minnow cells using Box-Behnken design. Optimized extraction conditions were deduced to be 50%/80 °C/7.5 h for ethanol concentration/extraction temperature/time, and OE-MTF showed contents of 6,8-diprenlygenistein ( 4 ), 2.09% with a MIC of 40 µg/mL. These results suggest that OE-MTF and its active isoflavones have promising potential as eco-friendly antibacterial agents against streptococcosis in aquaculture.

A new design of direct-contact membrane distillation (DCMD) modules with cross-diagonal carbon-fiber spacers of various hydrodynamic angles in flow channels to promote turbulence intensity was proposed to enhance pure water productivity. Attempts to reduce the temperature polarization coefficient were achieved by inserting cross-diagonal carbon-fiber spacers in channels, which create wakes and eddies in both heat and mass transfer behaviors to enhance the permeate flux enhancement. A simplified equation was formulated to obtain the theoretical predictions of heat transfer coefficients in the current DCMD device. The permeate fluxes and temperature distributions of both hot and cold feed streams are represented graphically with the inlet volumetric flow rate and inlet temperature of the hot saline feed stream as parameters. The higher distillate flux of countercurrent-flow operations for saline water desalination was accomplished as compared to the concurrent-flow operations of various hydrodynamic angles. The results show that the agreement between the theoretical predictions and experimental results is reasonably good. The effects of countercurrent-flow operations and inserting carbon fiber spacers have confirmed technical feasibility and device performance enhancement of up to 45%. The influences of operating and design parameters on the pure water productivity with the expense of energy consumption are also discussed.

Specific interactions between viruses and host cells provide essential insights into material science-based strategies to combat emerging viral diseases. pH-triggered viral fusion is ubiquitous to multiple viral families and is important for understanding the viral infection cycle. Inspired by this process, virus detection has been achieved using nanomaterials with host-mimetic membranes, enabling interactions with amphiphilic hemagglutinin fusion peptides of viruses. Most research has been on designing functional nanoparticles with fusogenic capability for virus detection, and there has been little exploitation of the kinetic stability to alter the ability of nanoparticles to interact with viral membranes and improve their sensing performance. In this study, a homogeneous fluorescent assay using self-assembled polymeric nanoparticles (PNPs) with tunable responsiveness to external stimuli is developed for rapid and straightforward detection of an activated influenza A virus. Dissociation of PNPs induced by virus insertion can be readily controlled by varying the fraction of hydrophilic segments in copolymers constituting PNPs, giving rise to fluorescence signals within 30 min and detection of various influenza viruses, including H9N2, CA04(H1N1), H4N6, and H6N8. Therefore, the designs demonstrated in this study propose underlying approaches for utilizing engineered PNPs through modulation of their kinetic stability for direct and sensitive identification of infectious viruses.

Neuromorphic devices have been investigated extensively for technological breakthroughs that could eventually replace conventional semiconductor devices. In contrast to other neuromorphic devices, the device proposed in this paper utilizes deep trap interfaces between the channel layer and the charge-inducing dielectrics (CID). The device was fabricated using in-situ atomic layer deposition (ALD) for the sequential deposition of the CID and oxide semiconductors. Upon the application of a gate bias pulse, an abrupt change in conducting states was observed in the device from the semiconductor to the metal. Additionally, numerous intermediate states could be implemented based on the number of cycles. Furthermore, each state persisted for 10,000 s after the gate pulses were removed, demonstrating excellent synaptic properties of the long-term memory. Moreover, the variation of drain current with cycle number demonstrates the device's excellent linearity and symmetry for excitatory and inhibitory behaviors when prepared on a glass substrate intended for transparent devices. The results, therefore, suggest that such unique synaptic devices with extremely stable and superior properties could replace conventional semiconducting devices in the future.

Background: The major limitation of arteriovenous graft access is the high incidence of thrombotic occlusion. This study investigated the outcomes of our salvage strategy for thrombosed hemodialysis arteriovenous grafts (including surgical thrombectomy with balloon angioplasty) and evaluated the efficacy of intragraft curettage., Methods: Salvage operations were performed for 290 thrombotic occluded arteriovenous grafts with clinical stenotic lesions from 2010 to 2018. Of these, 117 grafts received surgical thrombectomy and balloon angioplasty from 2010 to 2012 (group A), and 173 grafts received surgical thrombectomy and balloon angioplasty, with an additional salvage procedure using a curette and a graft thrombectomy catheter, from 2013 to 2018 (group B). Outcomes were described in terms of post-intervention primary patency and secondary patency rates., Results: The post-intervention primary patency rates in groups A and B were 44.2% and 66.1% at 6 months and 23.0% and 38.3% at 12 months, respectively (p=0.003). The post-intervention secondary patency rates were 87.6% and 92.6% at 6 months and 79.7% and 85.0% at 12 months, respectively (p=0.623). Multivariate Cox regression analysis demonstrated that intragraft curettage was a positive predictor of post-intervention primary patency (hazard ratio, 0.700; 95% confidence interval, 0.519-0.943; p=0.019)., Conclusion: Surgical thrombectomy and balloon angioplasty showed acceptable outcomes concerning post-intervention primary and secondary patency rates. Additionally, intragraft curettage may offer better patency to salvage thrombotic occluded arteriovenous grafts with intragraft stenosis.

Anaerobic digestion produces large quantities of digestate as a by-product, which can potentially be applied as an organic fertilizer, but untreated anaerobic digestate (AD) may contain phytotoxins and the large volume of AD makes transportation and storage difficult. This study explored two relatively inexpensive processing methods to improve the agronomic performance of AD as a fertilizer via vegetable cultivation experiments. We first investigated the effect of dilution on AD's performance using four leafy vegetables (Chinese spinach, water spinach, Chinese cabbage and lettuce). The optimal concentrations of the AD were 20-40% (v/v in 250 mL applications per single-plant pot) for all four vegetables based on shoot fresh weight and comparable to the control treatment using commercial fertilizer. AD application also introduced Synergistetes bacteria into the growing medium, but the overall bacterial diversity and composition were similar to those of the control treatment. Considering the nutrient separation in the liquid and solid fractions of AD and the need to reduce the volume, we then experimented with the recovery of nutrients from both the liquid and solid fractions by filtering AD using two types of wood-based biochar (100 g biochar: 1 L AD) before applying the AD-biochar residues as side dressing at 1% (w/w). Both types of biochar achieved yields comparable to the treatment using a commercial fertilizer for the three vegetables tested (kale, lettuce and rocket salad). Our results show that dilution and biochar filtration can improve the agronomic performance of AD, making it a sustainable substitute for commercial fertilizer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Microalgae have emerged as an effective dual strategy for bio-valorisation of food processing wastewater and food waste hydrolysate which favours microalgae cultivation into producing value-added by products mainly lipids, carbohydrates, and proteins to the advantages of bioplastic production. Moreover, various microalgae have successfully removed high amount of organic pollutants from food processing wastewater prior discharging into the environment. Innovation of microalgae cultivating in food processing wastewater greatly reduced the cost of wastewater treatment compared to conventional approach in terms of lower carbon emissions, energy consumption, and chemical usage while producing microalgae biomass which can benefit low-cost fertilizer and bioplastic applications. The study on several microalgae species has all successfully grown on food waste hydrolysates showing high exponential growth rate and biomass production rich in proteins, lipids, carbohydrates, and fatty acids. Multiple techniques have been implemented for the extraction of food wastes to be incorporate into the bioplastic production., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To develop unique small-molecule inhibitors of hepatitis C virus (HCV), thiophen urea (TU) derivatives were synthesised and screened for HCV entry inhibitory activities. Among them, seven TU compounds exhibited portent anti-viral activities against genotypes 1/2 (EC 50 < 30 nM) and subsequently, they were further investigated; based on the pharmacological, metabolic, pharmacokinetic, and safety profiles, J2H-1701 was selected as the optimised lead compound as an HCV entry inhibitor. J2H-1701 possesses effective multi-genotypic antiviral activity. The docking results suggested the potential interaction of J2H-1701 with the HCV E2 glycoprotein. These results suggest that J2H-1701 can be a potential candidate drug for the development of HCV entry inhibitors.

Astaxanthin (ASX), a red‑colored xanthophyll carotenoid, functions as an antioxidant or pro‑oxidant. ASX displays anticancer effects by reducing or increasing oxidative stress. Reactive oxygen species (ROS) promote cancer cell death by necroptosis mediated by receptor‑interacting protein kinase 1 (RIP1) and RIP3. NADPH oxidase is a major source of ROS that may promote necroptosis in some cancer cells. The present study aimed to investigate whether ASX induces necroptosis by increasing NADPH oxidase activity and ROS levels in gastric cancer AGS cells. AGS cells were treated with ASX with or without ML171 (NADPH oxidase 1 specific inhibitor), N‑acetyl cysteine (NAC; antioxidant), z‑VAD (pan‑caspase inhibitor) or Necrostatin‑1 (Nec‑1; a specific inhibitor of RIP1). As a result, ASX increased NADPH oxidase activity, ROS levels and cell death, and these effects were suppressed by ML171 and NAC. Furthermore, ASX induced RIP1 and RIP3 activation, ultimately inducing mixed lineage kinase domain‑like protein (MLKL) activation, lactate dehydrogenase (LDH) release and cell death. Moreover, the ASX‑induced decrease in cell viability was reversed by Nec‑1 treatment and RIP1 siRNA transfection, but not by z‑VAD. ASX did not increase the ratio of apoptotic Bax/anti‑apoptotic Bcl‑2, the number of Annexin V‑positive cells, or caspase‑9 activation, which are apoptosis indices. In conclusion, ASX induced necroptotic cell death by increasing NADPH oxidase activity, ROS levels, LDH release and the number of propidium iodide‑positive cells, as well as activating necroptosis‑regulating proteins, RIP1/RIP3/MLKL, in gastric cancer AGS cells. The results of this study demonstrated the necroptotic effect of ASX on gastric cancer AGS cells, which required NADPH oxidase activation and RIP1/RIP3/MLKL signaling in vitro .

Small molecule modulators of mitochondrial function have been attracted much attention in recent years due to their potential therapeutic applications for neurodegenerative diseases. The mitochondrial translocator protein (TSPO) is a promising target for such compounds, given its involvement in the formation of the mitochondrial permeability transition pore in response to mitochondrial stress. In this study, we performed a ligand-based pharmacophore design and virtual screening, and identified a potent hit compound, 7 ( VH34 ) as a TSPO ligand. After validating its biological activity against amyloid-β (Aβ) induced mitochondrial dysfunction and in acute and transgenic Alzheimer's disease (AD) model mice, we developed a library of analogs, and we found two most active compounds, 31 and 44 , which restored the mitochondrial membrane potential, ATP production, and cell viability under Aβ-induced mitochondrial toxicity. These compounds recovered learning and memory function in acute AD model mice with improved pharmacokinetic properties.

A protocol for the synthesis of α-tertiary amines was developed by iterative addition of carbon nucleophiles to N , N -dialkyl carboxamides. Nucleophilic 1,2-addition of organolithium reagents to carboxamides forms anionic tetrahedral carbinolamine (hemiaminal) intermediates, which are subsequently treated with bromotrimethylsilane (Me 3 SiBr) followed by organomagnesium (Grignard) reagents, organolithium reagents or tetrabutylammonium cyanide, affording α-tertiary amines. Employment of (trimethylsilyl)methylmagnesium bromide as the 2 nd nucleophile allowed for aza-Peterson olefination of the resulting α-tertiary (trimethylsilyl)methylamines with acidic work-up, resulting in the formation of 1,1-diarylethylenes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This study aimed to evaluate whether manipulation under anesthesia (MUA) affect clinical outcome including range of motion (ROM) and patient satisfaction after total knee arthroplasty (TKA). It is hypothesized that MUA improves clinical outcomes and patient satisfaction after primary TKA. This retrospective study analyzed 97 patients who underwent staged bilateral primary TKA. MUA of knee flexion more than 120 degrees was performed a week after index surgery just before operation of the opposite site. The first knees with MUA were classified as the MUA group and the second knees without MUA as the control group. ROM, Knee Society Knee Score, Knee Society Functional Score, Western Ontario and McMaster Universities (WOMAC) score, and patient satisfaction were assessed. Postoperative flexion was significantly greater in the MUA group during 6 months follow-up (6 weeks: 111.6 vs. 99.8 degrees, p  < 0.001; 3 months: 115.9 vs. 110.2 degrees, p  = 0.001; 6 months: 120.2 vs. 117.0 degrees, p  = 0.019). Clinical outcomes also showed similar results with knee flexion during 2 years follow-up. Patient satisfaction was significantly high in the MUA group during 12 months (3 months: 80.2 vs. 71.5, p  < 0.001; 6 months: 85.8 vs. 79.8, p  < 0.001; 12 months: 86.1 vs. 83.9, p  < 0.001; 24 months: 86.6 vs. 85.5, p  = 0.013). MUA yielded improvement of clinical outcomes including ROM, and patient satisfaction, especially in the early period after TKA. MUA in the first knee could be taken into account to obtain early recovery and to improve patient satisfaction in staged bilateral TKA., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: To evaluate the arthroscopic findings of subtalar joints, including interosseous talocalcaneal ligament (ITCL) tear, in patients with chronic lateral ankle instability (CLAI) and sinus tarsi pain., Methods: A total of 118 ankles (109 patients) having CLAI with sinus tarsi pain who had undergone subtalar arthroscopy and lateral ankle ligament surgery were evaluated. The medical records, radiologic images, and the arthroscopic images and videos were reviewed. ITCL tears were classified into 4 grades: grade 0 (no tear), grade 1 (mild), grade 2 (moderate), and grade 3 (severe). The efficacy of magnetic resonance imaging (MRI) in diagnosing ITCL tears was also evaluated by comparing preoperative official readings of MRI to arthroscopic findings. The pre- and postoperative functional scores were also assessed., Results: The overall tear rate of ITCL was 107/118 (90.7%). There were 29 ankles (23.6%) with grade 1, 42 ankles (35.6%) with grade 2, and 36 ankles (30.5%) with grade 3 tears. Isolated lateral ankle instability (LAI) was diagnosed in 43 ankles (36.4%), subtalar instability (STI) in 30 ankles (25.4%), and LAI with STI in 45 ankles (38.1%). There was a statistically significant relationship between the ITCL tear grade and the final diagnosis. ITCL tear was confirmed or suspected in 81 ankles (68.6%) on preoperative MRI. Pain Visual Analog Score and functional outcome scores including the American Orthopaedic Foot & Ankle Society and Karlsson-Peterson scores showed significant improvement after the surgery., Conclusion: A high rate (90.7%) of ITCL tears was noted in CLAI patients with sinus tarsi pain. ITCL damage may play an important role in subtalar instability in patients with CLAI and sinus tarsi pain. Subtalar arthroscopic evaluation for ITCL tear is important for correct diagnosis for CLAI with sinus tarsi pain., Level of Evidence: IV., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

While the coronavirus disease (COVID-19) accounts for the current global pandemic, the emergence of other unknown pathogens, named "Disease X," remains a serious concern in the future. Emerging or re-emerging pathogens continue to pose significant challenges to global public health. In response, the scientific community has been urged to create advanced platform technologies to meet the ever-increasing needs presented by these devastating diseases with pandemic potential. This review aims to bring new insights to allow for the application of advanced nanomaterials in future diagnostics, vaccines, and antiviral therapies, thereby addressing the challenges associated with the current preparedness strategies in clinical settings against viruses. The application of nanomaterials has advanced medicine and provided cutting-edge solutions for unmet needs. Herein, an overview of the currently available nanotechnologies is presented, highlighting the significant features that enable them to control infectious diseases, and identifying the challenges that remain to be addressed for the commercial production of nano-based products is presented. Finally, to conclude, the development of a nanomaterial-based system using a "One Health" approach is suggested. This strategy would require a transdisciplinary collaboration and communication between all stakeholders throughout the entire process spanning across research and development, as well as the preclinical, clinical, and manufacturing phases., (© 2021 Wiley-VCH GmbH.)

Hypotension in the early stages of life appears in 20% of very low birth weight (VLBW) infants. The gestational age and birth weight are the risk factors highly related to the postnatal hypotension. Other risk factors slightly differ between different studies. So, we evaluated the risk factors and prognosis that are associated with infants treated with hypotension in the early stages of life, after excluding the influences of gestational age and small for gestational age (SGA). VLBW infants registered in the Korean Neonatal Network between 2013 and 2015 treated for hypotension within a week after their birth were selected as study subjects. The rest were used as a control group. Risk factors and the prevalence of severe complications, including mortality, were investigated and compared after matching for gestational age and SGA. The treatment rate for hypotension within the first postnatal week was inversely related to decreasing gestational ages and birth weights. In particular, 63.4% of preterm infants born at ≤ 24 weeks' gestation and 66.9% of those with a birth weight < 500 g were treated for hypotension within a week of birth. Regression analysis after matching showed that 1-minute Apgar score, neonatal cardiac massage or epinephrine administration, symptomatic patent ductus arteriosus, early onset sepsis, and chorioamnionitis were significantly associated with hypotension. In the hypotension group, mortality, grade 3 or higher intraventricular hemorrhage, periventricular leukomalacia, and moderate to severe bronchopulmonary dysplasia rates were significantly higher after the matching for gestational age and SGA. Hypotension during the first postnatal week is very closely related to the prematurity and the condition of the infant shortly after birth. Regular prenatal care including careful monitoring and appropriate neonatal resuscitation are very crucial to decrease the risk of hypotension in the early stages of life., Competing Interests: The authors have declared that no competing interests exist.

Background: The effect of supramalleolar osteotomy without a bone marrow-stimulating procedure for articular cartilage regeneration in the ankle joint remains unknown. We investigated whether supramalleolar osteotomy yielded favorable clinical and radiographic outcomes. We also evaluated the joint tissue appearance after supramalleolar osteotomy without a bone marrow-stimulating procedure with use of second-look arthroscopy and its correlation with the outcome., Methods: Twenty-nine ankles were retrospectively reviewed at a mean of 2.9 years after supramalleolar osteotomy without a bone marrow-stimulating procedure. All 29 ankles had had second-look arthroscopy to evaluate tibiotalar joint tissue regeneration at a minimum of 1 year postoperatively. A visual analog scale (VAS) pain score, the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, and patient satisfaction were used for functional evaluations. Ankle osteoarthritis was classified with the Takakura staging system, and the tibial anterior surface (TAS) angle and tibial lateral surface (TLS) angle were measured on radiographs., Results: The mean VAS and AOFAS scores improved from 6.2 (95% confidence interval [CI], 5.7 to 6.8) preoperatively to 1.5 (95% CI, 0.9 to 2.1) postoperatively and from 60.5 (95% CI, 54.9 to 66.1) preoperatively to 88.3 (95% CI, 84.3 to 92.3) postoperatively, respectively. Patient satisfaction with the outcome of the procedure was classified as very satisfied or satisfied for 27 ankles (93.1%). Sixteen of 21 ankles that were classified as Takakura stage-IIIa and 2 of 3 ankles that were classified as stage-IIIb preoperatively improved to stage II postoperatively. The mean TAS and TLS angles significantly improved from 83.5° (95% CI, 82.2° to 84.7°) and 77.0° (95% CI, 75.4° to 78.7°) preoperatively to 94.2° (95% CI, 92.7° to 95.7°) and 80.4° (95% CI, 78.3° to 82.5°) postoperatively, respectively. On second-look arthroscopy, 26 ankles (89.7%) showed tissue regeneration of the medial compartment of the ankle joint and no patient showed cartilage deterioration., Conclusions: Medial tibiotalar tissue regeneration was identified in most patients with medial compartment ankle osteoarthritis following supramalleolar osteotomy without a bone marrow-stimulating procedure. The procedure results in satisfactory clinical and radiographic outcomes with high patient satisfaction., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G556)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)