Z-number based fuzzy MCDM models for analyzing non-traditional security threats to finance supply chains: A case study from Vietnam.

Non-traditional security (NTS) threats have a vast and profound impact on many aspects of economic, political, social, and many other areas, especially supply chain finance (SCF), particularly in countries like Vietnam, which potentially affects the economic efficiency of businesses' supply chain financial, thereby affecting the general economy of the country and the world. In order to prevent and minimize the negative impacts caused by NTS threats to SCF, this study was conducted to identify NTS threats affecting SCF in Vietnam, at the same time calculate the weight of the impact level and find out the cause and effect relationship between them. Solution strategies are also proposed and ranked, thereby serving as a reference basis for relevant parties to choose appropriate response solutions. Due to the multi-criteria nature of NTS threats, the multiple criteria decision-making (MCDM) method is used in combination with the Z-number concept and Fuzzy set theory to approach the problem of certainty and increase the accuracy of study. The NTS threats are first identified through a literature review and then validated for suitability using the DELPHI technique (DELPHI). Suitable threats will be determined by relationship, weighted by Decision Making Trial And Evaluation Laboratory (DEMATEL) method. Proposed strategies are ranked using the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method. The results indicate that there are 19 NTS factors affecting SCF in Vietnam, and the global economic downturn, pandemic and health crisis, financial crisis and cybersecurity risk are the four root cause factors with the most decisive influence. Businesses and concerns need to prioritize addressing these four threats because they not only have a strong impact but also entail many other threats. The two strategies considered to be the most effective are a sustainable practice and a risk-hedging strategy. Businesses, governments, and stakeholders also should pay attention to the macroeconomic environment, technology, and environment and build sustainable businesses, regularly monitoring economic fluctuations and creating plans to prevent risks.

The efficacy and tolerability of proteoglycan F in the treatment of knee osteoarthritis: A prospective, randomized, double-blind controlled trial.

Objective: To identify the efficacy and tolerability of Proteoglycan F in patients with primary knee OA.Design: A 24-week randomized, placebo-controlled, double-blind clinical trial with two arms: (1) Proteoglycan F (received 10 â€‹mg proteoglycan daily, for 24 weeks) and (2) control group (received placebo). Knee symptoms and joint cartilage status (evaluated by ultrasound and MRI of knee joints), quality of life, serum cytokine levels (IL-1ß and TNF-α), and safety evaluation were measured before, during, and after the treatment. Results: After 24-week treatment, pain reduction (in the KOOS pain score) of at least 20% and at least 50% (NRS scale) compared to baseline in the PGF group was significantly higher than those in the control group. The PGF group had greater reductions in the total scores of subchondral bone marrow edema, and bone cocoon under cartilage on knee MRI (classification according to WORMs), which were -2.27 (-4.0; -0.51) and -1.77 (-3.08; -0.46), respectively (p â€‹< â€‹0.05). The two groups had no statistically significant difference in knee ultrasound characteristics. After 4 weeks, 12, and 24 weeks compared to baseline, there was no statistically significant difference in levels of urea, creatinine, aspartate aminotransferase, and alanine aminotransferase within the group and between the two study groups. Conclusions: Salmon cartilage PG with 10 â€‹mg per day has potential to improve pain symptoms and subchondral bone marrow edema and bone cocoon under cartilage lesions in primary knee OA. However, the efficacy of PGF should be viewed with caution, and future studies are needed for more specific evaluation.

Integrated Antigenic and Nucleic Acid Detection in Single Virions and Extracellular Vesicles with Viral Content.

Virion-mediated outbreaks are imminent and despite rapid responses, continue to cause adverse symptoms and death. Therefore, tunable, sensitive, high-throughput assays are needed to help diagnose future virion-mediated outbreaks. Herein, we developed a tunable in situ assay to selectively enrich virions and extracellular vesicles (EVs) and simultaneously detect antigens and nucleic acids at a single-particle resolution. The Biochip Antigen and RNA Assay (BARA) enhanced sensitivities compared to quantitative reverse-transcription polymerase chain reaction (qRT-PCR), enabling the detection of virions in asymptomatic patients, genetic mutations in single virions, and enabling the continued long-term expression of viral RNA in the EV-enriched subpopulation in the plasma of patients with post-acute sequelae of COVID-19. BARA revealed highly accurate diagnoses of COVID-19 by simultaneously detecting the spike glycoprotein and nucleocapsid-encoding RNA in saliva and nasopharyngeal swab samples. Altogether, the single-particle detection of antigens and viral RNA provides a tunable framework for the diagnosis, monitoring, and mutation screening of current and future outbreaks. This article is protected by copyright. All rights reserved.

Iatrogenic femoral artery injury due to cerclage wiring for diaphyseal femoral fracture: A case report and review the literature.

INTRODUCTION AND IMPORTANCE: During femoral fracture osteosynthesis, the superficial femoral artery can be incarcerated in the cerclage wiring. We report a case that had an iatrogenic superficial femoral artery injury due to cerclage wiring during femoral osteosynthesis. CASE PRESENTATION: I reported a 57-year-old patient presented with a fracture at the distal third of the left femur. He had undergone a femoral nailing and a cerclage wiring. Four hours postoperative, his left leg was colder, and his dorsalis pedis and posterior tibial pulse were absent. A CTA revealed his left superficial femoral artery entrapment by cerclage wire. After cerclage removal, the superficial femoral artery and vein had normal flow. The dorsalis pedis and posterior tibial pulse could be palpated. One day following, there was no compromising of blood flow, sensation, or motor-nerve function. CLINICAL DISCUSSION: Cerclage wiring in the proximal half of the femur was less risk to the femoral artery than in the distal part. The SFA entrapment into a femoral cerclage wire requires an urgent diagnosis and treatment. A missed diagnosis could lead to necrosis of the lower extremity and even death. CONCLUSION: Our case shows that the superficial femoral artery can be incarcerated in the cerclage wiring during osteosynthesis. Cerclage wiring in the proximal half of the femur was less risk to the femoral artery than in the distal part. We recommend using a suitable cerclage passer precautionary in any femur fracture, particularly in the distal third of the femur. LEVEL OF EVIDENCE: A case report.

Development and validation of multiplex real-time PCR for simultaneous detection of six bacterial pathogens causing lower respiratory tract infections and antimicrobial resistance genes.

BACKGROUND: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract infections (LRTIs) globally, leading to substantial morbidity and mortality. The rapid increase of antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs are prescribed antibiotics empirically while awaiting several days for culture results. Rapid pathogen and AMR gene detection could prompt optimal antibiotic use and improve outcomes. METHODS: Here, we developed multiplex quantitative real-time PCR using EvaGreen dye and melting curve analysis to rapidly identify six major pathogens and fourteen AMR genes directly from respiratory samples. The reproducibility, linearity, limit of detection (LOD) of real-time PCR assays for pathogen detection were evaluated using DNA control mixes and spiked tracheal aspirate. The performance of RT-PCR assays was subsequently compared with the gold standard, conventional culture on 50 tracheal aspirate and sputum specimens of ICU patients. RESULTS: The sensitivity of RT-PCR assays was 100% for K. pneumoniae, A. baumannii, P. aeruginosa, E. coli and 63.6% for S. aureus and the specificity ranged from 87.5% to 97.6%. The kappa correlation values of all pathogens between the two methods varied from 0.63 to 0.95. The limit of detection of target bacteria was 1600 CFU/ml. The quantitative results from the PCR assays demonstrated 100% concordance with quantitative culture of tracheal aspirates. Compared to culture, PCR assays exhibited higher sensitivity in detecting mixed infections and S. pneumoniae. There was a high level of concordance between the detection of AMR gene and AMR phenotype in single infections. CONCLUSIONS: Our multiplex quantitative RT-PCR assays are fast and simple, but sensitive and specific in detecting six bacterial pathogens of LRTIs and their antimicrobial resistance genes and should be further evaluated for clinical utility.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Comparing the mechanical characteristics between leg lengthening using only an Ilizarov external fixator and leg lengthening over a nail using an external fixator manufactured in Vietnam.

PURPOSE: The mechanical characteristics of leg lengthening over a nail (LON) using an external fixator are not well known; specifically, the number of rings and K-wires required for this method has not been determined. This study aimed to compare the mechanical characteristics of leg LON using the simplest configuration for a domestic frame and those of leg lengthening using the Ilizarov frame alone. METHODS: The mechanical characteristics of cow tibial samples for lengthening over an intramedullary nail in combination with a domestic external fixator (LON samples) and for lengthening with the Ilizarov frame (Ilizarov samples) were evaluated by assessing axial compression, bending load, and torsional load. The research indices were compression stiffness, bending stiffness, torsion stiffness, yield axial load, ultimate axial load, yield bending load, and ultimate bending load. RESULTS: No statistically significant differences were observed in the compression stiffness, ultimate axial load, bending stiffness, and ultimate, yield bending forces between the Ilizarov samples and LON samples. The compressive stiffness, yield axial load, and ultimate axial load of the LON samples were 98 ± 1.31 N/mm, 915 ± 23.89 N, and 1032 ± 29.86 N, respectively. The anterior-posterior bending stiffness and lateral bending stiffness of the LON samples were 122.48 ± 2.92 N/mm and 116.34 ± 3.95 N/mm, respectively. The yield anterior-posterior bending and ultimate anterior-posterior bending forces of the LON samples were 616.4 ± 3.64 N and 753.2 ± 3.49 N, respectively. The yield lateral bending and ultimate lateral bending forces of the LON samples were 624.6 ± 4.04 N and 759.0 ± 3.39 N, respectively. The axial torsional stiffness of the LON samples was 1.73 ± 0.05 N m/°, which was significantly lower than that of the Ilizarov samples (2.63 ± 0.03 N m/°). CONCLUSION: No statistically significant differences were observed in the mechanical fixation characteristics of axial compression and bending between the Ilizarov samples and LON samples. However, the axial torsional stiffness of the Ilizarov samples was statistically greater than that of the LON samples. We recommend using the simplest configuration for domestic frames in combination with LON for limb lengthening. Partial weight-bearing is permitted in the distraction stage. LEVEL OF EVIDENCE: Case-control study.

Engineering a tunable micropattern-array assay to sort single extracellular vesicles and particles to detect RNA and protein in situ.

The molecular heterogeneity of extracellular vesicles (EVs) and the co-isolation of physically similar particles, such as lipoproteins (LPs), confounds and limits the sensitivity of EV bulk biomarker characterization. Herein, we present a single-EV and particle (siEVP) protein and RNA assay (siEVP PRA) to simultaneously detect mRNAs, miRNAs, and proteins in subpopulations of EVs and LPs. The siEVP PRA immobilizes and sorts particles via positive immunoselection onto micropatterns and focuses biomolecular signals in situ. By detecting EVPs at a single-particle resolution, the siEVP PRA outperformed the sensitivities of bulk-analysis benchmark assays for RNA and protein. To assess the specificity of RNA detection in complex biofluids, EVs from various glioma cell lines were processed with small RNA sequencing, whereby two mRNAs and two miRNAs associated with glioblastoma multiforme (GBM) were chosen for cross-validation. Despite the presence of single-EV-LP co-isolates in serum, the siEVP PRA detected GBM-associated vesicular RNA profiles in GBM patient siEVPs. The siEVP PRA effectively examines intravesicular, intervesicular, and interparticle heterogeneity with diagnostic promise.

Vericiguat.

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433.

DaGzang: a synthetic data generator for cross-domain recommendation services.

Research on cross-domain recommendation systems (CDRS) has shown efficiency by leveraging the overlapping associations between domains in order to generate more encompassing user models and better recommendations. Nonetheless, if there is no dataset belonging to a specific domain, it is a challenge to generate recommendations in CDRS. In addition, finding these overlapping associations in the real world is generally tricky, and it makes its application to actual services hard. Considering these issues, this study aims to present a synthetic data generation platform (called DaGzang) for cross-domain recommendation systems. The DaGzang platform works according to the complete loop, and it consists of the following three steps: (i) detecting the overlap association (data distribution pattern) between the real-world datasets, (ii) generating synthetic datasets based on these overlap associations, and (iii) evaluating the quality of the generated synthetic datasets. The real-world datasets in our experiments were collected from Amazon's e-commercial website. To validate the usefulness of the synthetic datasets generated from DaGzang, we embed these datasets into our cross-domain recommender system, called DakGalBi. We then evaluate the recommendations generated from DakGalBi with collaborative filtering (CF) algorithms, user-based CF, and item-based CF. Mean absolute error (MAE) and root mean square error (RMSE) metrics are measured to evaluate the performance of collaborative filtering (CF) CDRS. In particular, the highest performance of the three recommendation methods is user-based CF when using 10 synthetic datasets generated from DaGzang (0.437 at MAE and 0.465 at RMSE).

Encapsulation of Human Umbilical Cord Mesenchymal Stem Cells in LunaGel Photocrosslinkable Extracellular Matrix and Subcutaneous Transplantation in Mice.

Stem cells have significant potential in regenerative medicines. However, a major issue with implanting stem cells in the regeneration of new tissue is the methods to implant them and cell viability and functions before and after implantation. Here we developed a simple yet effective method that used photo-crosslinkable gelatin-based hydrogel (LunaGelTM) as a scaffold for the encapsulation, expansion, and eventually, transplantation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) into mice subcutaneously. We demonstrated the proliferation and maintenance of the original expression of mesenchymal stem cell markers as well as the ability to differentiate into mesoderm-derived cells. The hydrogel was highly stable with no signs of degradation after 20 days in PBS. The hUC-MSCs remained viable after transplantation into mice's subcutaneous pockets and migrated to integrate with the surrounding tissues. We showed a collagen-rich layer surrounding the transplanted cell-laden scaffold indicating the effects of growth factors secreted by the hUC-MSCs. A connective tissue layer was found between the implanted cell-laden scaffold and the collagen layer, and immunohistochemical staining results suggested that this tissue was derived from the MSCs which migrated from within the scaffold. The results, thus, also suggested a protective effect the scaffold has on the encapsulated cells from the antibodies and cytotoxic cells of the host immune system.

Treatment of 18 cm lower limb length discrepancy using lengthening over nail technique in tibia and lengthening and plating in femur - A case report.

INTRODUCTION AND IMPORTANCE: The management of extreme limb-length discrepancy remains a challenge for surgeons. Limb lengthening using an external fixator is a popular method for managing limb-length discrepancy; however, it had many complications. Other techniques using external fixators have been described, such as lengthening over a nail (LON) technique and lengthening and then plating (LATP), which decrease external fixator duration, equinus contracture, pin-site infection, bone alignment, and bone fracture. Only a few cases of management of extreme limb-length discrepancy due to hip dysplasia using LATP and LON techniques are reported in the literature. CASE PRESENTATION: We report a 24-year-old case of an 18 cm lower limb length discrepancy, who had tibial lengthening and Chiari pelvic osteotomy for treatment of congenital hip dislocation 12 years ago. The treatment for the patient was underwent the lengthening over nail technique in the tibia and lengthening and then plating in the femur. 9 months post-operative, the tibia and femur are union. The patient reported no pain and could walk and climb stairs without a crutch. CLINICAL DISCUSSION: Following pelvic osteotomy, leg lengthening is a good treatment for limb-length discrepancy due to hip dysplasia. The LON technique or LATN in the tibia and in the femur is an alternative choice for the treatment of extreme limb-length discrepancy. Lengthening and then plating could be widely employed in patients who are not suitable for the LON technique. Although the patient had gained the 18 cm lengthening, the range of motion of the left knee joint and left ankle joint was unrestricted, and without neurovascular complication. CONCLUSION: Following pelvic osteotomy, LON technique in the tibia and or LATP in the femur is considered an alternative choice for the treatment of extreme limb-length discrepancy due to hip dysplasia. LATP should be widely employed in patients who are not suitable for limb lengthening over a nail. LEVEL OF EVIDENCE: A case report.

Fabrication of an inverse opal structure of a hybrid metal-conducting polymer for plasmon-induced hyperthermia applications.

This paper describes the effective fabrication of an inverse opal (IO) structure for plasmon-induced hyperthermia applications using silver nanoparticles (AgNPs) doped in a conducting polymer of poly(3,4-ethylene dioxythiophene) (PEDOT). Indium tin oxide (ITO) substrates were firstly modified electrochemically by a layer of the inverse opal structure of PEDOT (IO-PEDOT). These as-prepared electrodes were subsequently used as working electrodes for electrodepositing AgNPs. The presence of plasmonic AgNPs doped inside a polymer network caused the hybrid of IO-PEDOT and AgNPs to generate significantly more heat than thin-film PEDOT, thin-film PEDOT/AgNPs, and IO-PEDOT under 532 nm laser irradiation. This is attributed to the synergistic effect of the large active area inverse opal structure and doped AgNPs, which exhibit more thermal energy and heat faster than the individual component structures. These findings point to a wide range of potential applications for hybrid IO-PEDOT/AgNPs in hyperthermia treatment.

Design and evaluation of novel analogs of 2-amino-4-boronobutanoic acid (ABBA) as inhibitors of human gamma-glutamyl transpeptidase.

Inhibitors of gamma-glutamyl transpeptidase (GGT1, aka gamma-glutamyl transferase) are needed for the treatment of cancer, cardiovascular illness and other diseases. Compounds that inhibit GGT1 have been evaluated in the clinic, but no inhibitor has successfully demonstrated specific and systemic GGT1 inhibition. All have severe side effects. L-2-amino-4­boronobutanoic acid (l-ABBA), a glutamate analog, is the most potent GGT1 inhibitor in vitro. In this study, we have solved the crystal structure of human GGT1 (hGGT1) with ABBA bound in the active site. The structure was interrogated to identify interactions between the enzyme and the inhibitor. Based on these data, a series of novel ABBA analogs were designed and synthesized. Their inhibitory activity against the hydrolysis and transpeptidation activities of hGGT1 were determined. The lead compounds were crystalized with hGGT1 and the structures solved. The kinetic data and structures of the complexes provide new insights into the critical role of protein structure dynamics in developing compounds for inhibition of hGGT1.

An immunogold single extracellular vesicular RNA and protein (Au SERP) biochip to predict responses to immunotherapy in non-small cell lung cancer patients.

Conventional PD-L1 immunohistochemical tissue biopsies only predict 20%-40% of non-small cell lung cancer (NSCLC) patients that will respond positively to anti-PD-1/PD-L1 immunotherapy. Herein, we present an immunogold biochip to quantify single extracellular vesicular RNA and protein (Au SERP) as a non-invasive alternative. With only 20 µl of purified serum, PD-1/PD-L1 proteins on the surface of extracellular vesicles (EVs) and EV PD-1/PD-L1 messenger RNA (mRNA) cargo were detected at a single-vesicle resolution and exceeded the sensitivities of their bulk-analysis conventional counterparts, ELISA and qRT-PCR, by 1000 times. By testing a cohort of 27 non-responding and 27 responding NSCLC patients, Au SERP indicated that the single-EV mRNA biomarkers surpass the single-EV protein biomarkers in predicting patient responses to immunotherapy. Dual single-EV PD-1/PD-L1 mRNA detection differentiated responders from non-responders with an accuracy of 72.2% and achieved an NSCLC diagnosis accuracy of 93.2%, suggesting the potential for Au SERP to provide enhanced immunotherapy predictions and cancer diagnoses within the clinical setting.

Water Harvesting Strategies through Solar Steam Generator Systems.

Solar steam generator (SSG) systems have attracted increasing attention, owing to its simple manufacturing, material abundance, cost-effectiveness, and environmentally friendly freshwater production. This system relies on photothermic materials and water absorbing substrates for a clean continuous distillation process. To optimize this process, there are factors that are needed to be considered such as selection of solar absorber and water absorbent materials, followed by micro/macro-structural system design for efficient water evaporation, floating, and filtration capability. In this contribution, we highlight the general interfacial SSG concept, review and compare recent progresses of different SSG systems, as well as discuss important factors on performance optimization. Furthermore, unaddressed challenges such as SSG's cost to performance ratio, filtration of untreatable micropollutants/microorganisms, and the need of standardization testing will be discussed to further advance future SSG studies.

Effects of harvesting on morphological and biochemical characteristics of microalgal biomass harvested by polyacrylamide addition, pH-induced flocculation, and centrifugation.

The effects of microalgae harvesting methods on microalgal biomass quality were evaluated using three species namely the freshwater green alga Chlorella vulgaris, marine red alga Porphyridium purpureum and marine diatom Phaeodactylum tricornutum. Harvesting efficiencies of polyacrylamide addition, alkaline addition, and centrifugation ranged from 85 to 95, 59-92 and 100%, respectively, across these species. Morphology of the harvested cells (i.e. compromised cell walls) was significantly impacted by alkaline pH-induced flocculation for all three species. Over 50% of C. vulgaris cells were compromised with alkaline pH compared to < 10% with polyacrylamide and centrifugation. The metabolic profiles varied depending on harvesting methods. Species-specific decrease of certain metabolites was observed. These results suggest that the method of harvest can alter the metabolic profile of the biomass amongst the three harvesting methods, polyacrylamide addition showed higher harvesting efficiency with less compromised cells and higher retention of industry important biochemicals.

Chiral Inversion of 2-Arylpropionic Acid Enantiomers under Anaerobic Conditions.

This work examined the chiral inversion of 2-arylpropionic acids (2-APAs) under anaerobic conditions and the associated microbial community. The anaerobic condition was simulated by two identical anaerobic digesters. Each digester was fed with the substrate containing 11 either pure (R)- or pure (S)-2-APA enantiomers. Chiral inversion was evidenced by the concentration increase of the other enantiomer in the digestate and the changes in the enantiomeric fraction between the two enantiomers. Both digesters showed similar and poor removal of 2-APAs (≤30%, except for naproxen) and diverse chiral inversion behaviors under anaerobic conditions. Four compounds exhibited (S → R) unidirectional inversion [flurbiprofen, ketoprofen, naproxen, and 2-(4-tert-butylphenyl)propionic acid], and the remaining seven compounds showed bidirectional inversion. Several aerobic and facultative anaerobic bacterial genera (Candidatus Microthrix, Rhodococcus, Mycobacterium, Gordonia, and Sphingobium) were identified in both digesters and predicted to harbor the 2-arylpropionyl-CoA epimerase (enzyme involved in chiral inversion) encoding gene. These genera presented at low abundances, <0.5% in the digester dosed with (R)-2-APAs and <0.2% in the digester dosed with (S)-2-APAs. The low abundances of these genera explain the limited extent of chiral inversion observed in this study.

Microalgae-bacteria consortium for wastewater treatment and biomass production.

The diversity of microalgae and bacteria allows them to form a complementary consortium for efficient wastewater treatment and nutrient recovery. This review highlights the potential of wastewater-derived microalgal biomass as a renewable feedstock for producing animal feed, biofertilisers, biofuel, and many valuable biochemicals. Data corroborated from this review shows that microalgae and bacteria can thrive in many environments. Microalgae are especially effective at utilising nutrients from the water as they grow. This review also consolidates the current understanding of microalgae characteristics and their interactions with bacteria in a consortium system. Recent studies on the performance of only microalgae and microalgae-bacteria wastewater treatment are compared and discussed to establish a research roadmap for practical implementation of the consortium systems for various wastewaters (domestic, industrial, agro-industrial, and landfill leachate wastewater). In comparison to the pure microalgae system, the consortium system has a higher removal efficiency of up to 15% and shorter treatment time. Additionally, this review addresses a variety of possibilities for biomass application after wastewater treatment.

Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double-blind, randomised controlled phase 1 and 2 trial.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.