The presence of broadly neutralizing anti-SARS-CoV-2 RBD antibodies elicited by primary series and booster dose of COVID-19 vaccine.

Antibody-mediated immunity plays a key role in protection against SARS-CoV-2. We characterized B-cell-derived anti-SARS-CoV-2 RBD antibody repertoires from vaccinated and infected individuals and elucidate the mechanism of action of broadly neutralizing antibodies and dissect antibodies at the epitope level. The breadth and clonality of anti-RBD B cell response varies among individuals. The majority of neutralizing antibody clones lose or exhibit reduced activities against Beta, Delta, and Omicron variants. Nevertheless, a portion of anti-RBD antibody clones that develops after a primary series or booster dose of COVID-19 vaccination exhibit broad neutralization against emerging Omicron BA.2, BA.4, BA.5, BQ.1.1, XBB.1.5 and XBB.1.16 variants. These broadly neutralizing antibodies share genetic features including a conserved usage of the IGHV3-53 and 3-9 genes and recognize three clustered epitopes of the RBD, including epitopes that partially overlap the classically defined set identified early in the pandemic. The Fab-RBD crystal and Fab-Spike complex structures corroborate the epitope grouping of antibodies and reveal the detailed binding mode of broadly neutralizing antibodies. Structure-guided mutagenesis improves binding and neutralization potency of antibody with Omicron variants via a single amino-substitution. Together, these results provide an immunological basis for partial protection against severe COVID-19 by the ancestral strain-based vaccine and indicate guidance for next generation monoclonal antibody development and vaccine design.

Are high-throughput root phenotyping platforms suitable for informing root system architecture models with genotype-specific parameters? An evaluation based on the root model ArchiSimple and a small panel of wheat cultivars.

Given the difficulties in accessing plant roots in situ, high-throughput root phenotyping (HTRP) platforms under controlled conditions have been developed to meet the growing demand for characterizing root system architecture (RSA) for genetic analyses. However, a proper evaluation of their capacity to provide the same estimates for strictly identical root traits across platforms has never been achieved. In this study, we performed such an evaluation based on six major parameters of the RSA model ArchiSimple, using a diversity panel of 14 bread wheat cultivars in two HTRP platforms that had different growth media and non-destructive imaging systems together with a conventional set-up that had a solid growth medium and destructive sampling. Significant effects of the experimental set-up were found for all the parameters and no significant correlations across the diversity panel among the three set-ups could be detected. Differences in temperature, irradiance, and/or the medium in which the plants were growing might partly explain both the differences in the parameter values across the experiments as well as the genotype × set-up interactions. Furthermore, the values and the rankings across genotypes of only a subset of parameters were conserved between contrasting growth stages. As the parameters chosen for our analysis are root traits that have strong impacts on RSA and are close to parameters used in a majority of RSA models, our results highlight the need to carefully consider both developmental and environmental drivers in root phenomics studies.

LRRC8A anion channels modulate vascular reactivity via association with myosin phosphatase rho interacting protein.

Leucine-rich repeat containing 8A (LRRC8A) volume regulated anion channels (VRACs) are activated by inflammatory and pro-contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II and stretch. LRRC8A associates with NADPH oxidase 1 (Nox1) and supports extracellular superoxide production. We tested the hypothesis that VRACs modulate TNFα signaling and vasomotor function in mice lacking LRRC8A exclusively in vascular smooth muscle cells (VSMCs, Sm22α-Cre, Knockout). Knockout (KO) mesenteric vessels contracted normally but relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) was enhanced compared to wild type (WT). Forty-eight hours of ex vivo exposure to TNFα (10 ng/mL) enhanced contraction to norepinephrine (NE) and markedly impaired dilation to ACh and SNP in WT but not KO vessels. VRAC blockade (carbenoxolone, CBX, 100 µM, 20 min) enhanced dilation of control rings and restored impaired dilation following TNFα exposure. Myogenic tone was absent in KO rings. LRRC8A immunoprecipitation followed by mass spectroscopy identified 33 proteins that interacted with LRRC8A. Among them, the myosin phosphatase rho-interacting protein (MPRIP) links RhoA, MYPT1 and actin. LRRC8A-MPRIP co-localization was confirmed by confocal imaging of tagged proteins, Proximity Ligation Assays, and IP/western blots. siLRRC8A or CBX treatment decreased RhoA activity in VSMCs, and MYPT1 phosphorylation was reduced in KO mesenteries suggesting that reduced ROCK activity contributes to enhanced relaxation. MPRIP was a target of redox modification, becoming oxidized (sulfenylated) after TNFα exposure. Interaction of LRRC8A with MPRIP may allow redox regulation of the cytoskeleton by linking Nox1 activation to impaired vasodilation. This identifies VRACs as potential targets for treatment or prevention of vascular disease.

Improved expression and purification of highly-active 3 chymotrypsin-like protease from SARS-CoV-2.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease-19 (COVID-19). The COVID-19 pandemic has resulted in millions of deaths and widespread socio-economic damage worldwide. Therefore, numerous studies have been conducted to identify effective measures to control the spreading of the virus. Among various potential targets, the 3 chymotrypsin-like protease (3CLpro), also known as Mpro, stands out as the key protease of SARS-CoV-2, playing an essential role in virus replication and assembly, is the most prospective. In this study, we modified the commercial vector, pETM33-Nsp5-Mpro (plasmid # 156475, Addgene, USA), by inserting an autocleavage site (AVLQ) of 3CLpro and 6 × His-tag encoding sequences before and after the Nsp5-Mpro sequence, respectively. This modification enabled the expression of 3CLpro as an authentic N terminal protease (au3CLpro), which was purified to electrophoretic homogeneity by a single-step chromatography using two tandem Glutathione- and Ni-Sepharose columns. The enzyme au3CLpro demonstrated significantly higher activity (3169 RFU/min/µg protein) and catalytic efficiency (Kcat/Km of 0.007 µM-1.s-1) than that of the 3CLpro (com3CLpro) expressed from the commercial vector (pETM33-Nsp5-Mpro) with specific activity 889 RFU/min/µg and Kcat/Km of 0.0015 µM-1.s-1, respectively. Optimal conditions for au3CLpro activity included a 50 mM Tris-HCl buffer at pH 7, containing 150 mM NaCl and 0.1 mg/ml BSA at 37 °C.

Three Pillars of Support for Orphan Drug Programs: Individual Valuations, Societal Valuations, and Anonymous Altruism.

OBJECTIVES: To identify and describe potential societal and individual sources of support for orphan drug programs. METHODS: The generalized risk-adjusted cost-effectiveness (GRACE) method shows that acute illness and disability severity increase individuals' willingness to pay (WTP) for health gains. We develop a social welfare function (SWF) that incorporates individuals' own values, combined with politically- or ethically determined weights. We introduce the concept of horizontal equity-that individuals in similar situations should be treated similarly-into the SWF. Finally, we introduce anonymous altruism into individuals' utility functions-the desire to help others, without knowing their identity. RESULTS: Combined with the empirical link between disease severity and rarity, GRACE demonstrates heightened WTP for health gains, leading rational individuals to support orphan drug programs, our first pillar of support. Adding horizontal equity to the SWF further increases societal support for orphan drug programs. Anonymous altruism, focusing most strongly on those in the most-dire circumstances, leads to altruistic support for those with severe disorders. Because innovators' economic incentives lead them to focus on larger markets, anonymous altruistic individuals to specifically support orphan drug programs. The presence of free-rider problems translates this into public program support. CONCLUSIONS: We identify supporting three pillars for orphan drug programs: (1) individuals' desire for treatments to treat rare disease that are often severe and life-threatening; (2) the concept of horizontal equity in our SWF: (3) anonymous altruism, the desire to people, even when unknown, in dire circumstances.

On Inactivation of the Coronavirus Main Protease.

A deeper understanding of the inactive conformations of the coronavirus main protease (MPro) could inform the design of allosteric drugs. Based on extensive molecular dynamics simulations, we built a Markov State Model to investigate structural changes that can inactivate the SARS-CoV-2 MPro. In a subset of structures, one subunit of the homodimer assumes an inactive conformation that resembles an inactive crystal structure. However, contradicting the widely held half-of-sites activity hypothesis, the most populated enzyme structures have two active subunits. We then used transition path theory (TPT) and the Jensen-Shannon Divergence (JSD) to pinpoint residues involved in the inactivation process. A π stack between Phe140 and His163 is a key feature that can distinguish active and inactive conformations of MPro. Each subunit has unique inactive conformations stabilized by π stacking interactions involving residues Phe140, Tyr118, His163, and His172, a hydrogen bonding network centered around His163 and His172, and a modified network of interactions in the dimer interface. The importance of these residues in maintaining an active structure explains the sensitivity of enzymatic activity to site-directed mutagenesis.

Implementing living-donor pediatric liver transplantation in Southern Vietnam: 15-year results and perspectives.

BACKGROUND: ND2 in Ho Chi Minh City is currently the only public center that performs PLT in Southern Vietnam. In 2005, the first PLT was successfully performed, with support from Belgian experts. This study reviews the implementation of PLT at our center and evaluates the results and challenges. METHODS: Implementation of PLT at ND2 required medico-surgical team building and extensive improvement of hospital facilities. Records of 13 transplant recipients from 2005 to 2020 were studied retrospectively. Short- and long-term complications, as well as the survival rates, were reported. RESULTS: The mean follow-up time was 8.3 ± 5.7 years. Surgical complications included one case of hepatic artery thrombosis that was successfully repaired, one case of colon perforation resulting in death from sepsis, and two cases of bile leak that were drained surgically. PTLD was observed in five patients, of whom three died. There were no cases of retransplantation. The 1-year, 5-year, and 10-year patient survival rates were 84.6%, 69.2%, and 69.2%, respectively. There were no cases of complication or death among the donors. CONCLUSION: Living-donor PLT was developed at ND2 for providing a life-saving treatment to children with end-stage liver disease. Early surgical complication rate was low, and the patient survival rate was satisfactory at 1 year. Long-term survival decreased considerably due to PTLD. Future challenges include surgical autonomy and improvement of long-term medical follow-up with a particular emphasis on prevention and management of Epstein-Barr virus-related disease.

The Acyl-Proteome of Syntrophus aciditrophicus Reveals Metabolic Relationships in Benzoate Degradation.

Syntrophus aciditrophicus is a model syntrophic bacterium that degrades fatty and aromatic acids into acetate, CO2, formate, and H2 that are utilized by methanogens and other hydrogen-consuming microbes. S. aciditrophicus benzoate degradation proceeds by a multistep pathway with many intermediate reactive acyl-coenzyme A species (RACS) that can potentially Nε-acylate lysine residues. Herein, we describe the identification and characterization of acyl-lysine modifications that correspond to RACS in the benzoate degradation pathway. The amounts of modified peptides are sufficient to analyze the post-translational modifications without antibody enrichment, enabling a range of acylations located, presumably, on the most extensively acylated proteins throughout the proteome to be studied. Seven types of acyl modifications were identified, six of which correspond directly to RACS that are intermediates in the benzoate degradation pathway including 3-hydroxypimeloylation, a modification first identified in this system. Indeed, benzoate-degrading enzymes are heavily represented among the acylated proteins. A total of 125 sites were identified in 60 proteins. Functional deacylase enzymes are present in the proteome, indicating a potential regulatory system/mechanism by which S. aciditrophicus modulates acylation. Uniquely, Nε-acyl-lysine RACS are highly abundant in these syntrophic bacteria, raising the compelling possibility that post-translational modifications modulate benzoate degradation in this and potentially other, syntrophic bacteria. Our results outline candidates for further study of how acylations impact syntrophic consortia.

Induction of Human Wharton's Jelly of Umbilical Cord Derived Mesenchymal Stem Cells to Be Chondrocytes and Transplantation in Guinea Pig Model with Spontaneous Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease commonly found in elderly people and obese patients. Currently, OA treatments are determined based on their condition severity and a medical professional's advice. The aim of this study was to differentiate human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) into chondrocytes for transplantation in OA-suffering guinea pigs. hWJ-MSCs were isolated using the explant culture method, and then, their proliferation, phenotypes, and differentiation ability were evaluated. Subsequently, hWJ-MSCs-derived chondrocytes were induced and characterized based on immunofluorescent staining, qPCR, and immunoblotting techniques. Then, early-OA-suffering guinea pigs were injected with hyaluronic acid (HA) containing either MSCs or 14-day-old hWJ-MSCs-derived chondrocytes. Results showed that hWJ-MSCs-derived chondrocytes expressed specific markers of chondrocytes including Aggrecan, type II collagen, and type X collagen proteins and ß-catenin, Sox9, Runx2, Col2a1, Col10a1, and ACAN gene expression markers. Administration of HA plus hWJ-MSCs-derived chondrocytes (HA-CHON) produced a better recovery rate of degenerative cartilages than HA plus MSCs or only HA. Histological assessments demonstrated no significant difference in Mankin's scores of recovered cartilages between HA-CHON-treated guinea pigs and normal articular cartilage guinea pigs. Transplantation of hWJ-MSCs-derived chondrocytes was more effective than undifferentiated hWJ-MSCs or hyaluronic acid for OA treatment in guinea pigs. This study provides a promising treatment to be used in early OA patients to promote recovery and prevent disease progression to severe osteoarthritis.

Optimal timing of PD-1 blockade in combination with oncolytic virus therapy.

Anti-PD-1 and oncolytic viruses (OVs) have non-overlapping anti-tumor mechanisms, since each agent works at different steps of the cancer-immunity cycle. Evidence suggests that OVs improve therapeutic responses to anti-PD-1 therapy by reversing immunosuppressive factors, increasing the number and diversity of infiltrating lymphocytes, and promoting PD-L1 expression in both injected and non-injected tumors. Many studies in preclinical models suggest that the timing of anti-PD-1 administration influences the therapeutic success of the combination therapy (anti-PD-1 + OV). Therefore, determining the appropriate sequencing of agents is of critical importance to designing a rationale OV-based combinational clinical trial. Currently, the combination of anti-PD-1 and OVs are being delivered using various schedules, and we have classified the timing of administration of anti-PD-1 and OVs into five categories: (i) anti-PD-1 lead-in → OV; (ii) concurrent administration; (iii) OV lead-in → anti-PD-1; (iv) concurrent therapy lead-in → anti-PD-1; and (v) OV lead-in → concurrent therapy. Based on the reported preclinical and clinical literature, the most promising treatment strategy to date is hypothesized to be OV lead-in → concurrent therapy. In the OV lead-in → concurrent therapy approach, initial OV treatment results in T cell priming and infiltration into tumors and an immunologically hot tumor microenvironment (TME), which can be counterbalanced by engagement of PD-L1 to PD-1 receptor on immune cells, leading to T cell exhaustion. Therefore, after initial OV therapy, concurrent use of both OV and anti-PD-1 is critical through which OV maintains T cell priming and an immunologically hot TME, whereas PD-1 blockade helps to overcome PD-L1/PD-1-mediated T cell exhaustion. It is important to note that the hypothetical conclusion drawn in this review is based on thorough literature review on current understanding of OV + anti-PD-1 combination therapies and rhythm of treatment-induced cancer-immunity cycle. A variety of confounding factors such as tumor types, OV types, presence or absence of cytokine transgenes carried by an OV, timing of treatment initiation, varying dosages and treatment frequencies/duration of OV and anti-PD-1, etc. may affect the validity of our conclusion that will need to be further examined by future research (such as side-by-side comparative studies using all five treatment schedules in a given tumor model).

Spatial regulation of RBOHD via AtECA4-mediated recycling and clathrin-mediated endocytosis contributes to ROS accumulation during salt stress response but not flg22-induced immune response.

Various environmental stresses can induce production of reactive oxygen species (ROS) to turn on signaling for proper responses to those stresses. Plasma membrane (PM)-localized respiratory burst oxidase homologs (RBOHs), in particular RBOHD, produce ROS via the post-translational activation upon abiotic and biotic stresses. Although the mechanisms of RBOHD activation upon biotic stress have been elucidated in detail, it remains elusive how salinity stress activates RBOHD. Here, we present evidence that trafficking of PM-localized RBOHD to endosomes and then its recycling back to the PM is critical for ROS accumulation upon salinity stress. ateca4 plants that were defective in recycling of proteins from endosomes to the PM and clc2-1 and chc2-1 plants that were defective in endocytosis showed a defect in salinity stress-induced ROS production. In addition, ateca4 plants showed a defect in transient accumulation of GFP:RBOHD to the PM at the early stage of salinity stress. By contrast, ateca4 plants showed no defect in the increase in the ROS level and accumulation of RBOHD to the PM upon flg22 treatment as wild-type plants. Based on these observations, we propose that factors involved in the trafficking machinery such as AtECA4 and clathrin are important players in salt stress-induced, but not flg22-induced, ROS accumulation.

Monkeypox Virus Infection in 2 Female Travelers Returning to Vietnam from Dubai, United Arab Emirates, 2022.

Mpox was diagnosed in 2 women returning to Vietnam from the United Arab Emirates. The monkeypox viruses belonged to an emerging sublineage, A.2.1, distinct from B.1, which is responsible for the ongoing multicountry outbreak. Women could contribute to mpox transmission, and enhanced genomic surveillance is needed to clarify pathogen evolution.

Associations between four polymorphisms of the SLCO1B1 and effectiveness of the statins: a meta-analysis.

OBJECTIVE: Statins are the first-choice therapy for dyslipidemia, but their effectiveness can be influenced by genetic polymorphisms. This study was conducted to assess the association of variants of the solute carrier anion transporter family 1B1 (SLCO1B1) gene, which encodes a transporter involving the hepatic clearance of the statins and their therapeutic efficacy. METHOD: A systematic review was performed on four electronic databases to identify relevant studies. The pooled mean difference with 95% confidence interval (CI) in percentage change of concentration of LDL-C, total cholesterol (TC), HDL-C, and triglycerides was calculated. Heterogeneity between studies and publication bias, subgroup analyses, and sensitivity analyses were also carried out using R software. RESULTS: Twenty-one studies on 24 365 participants and four variants [rs4149056 (c.521T>C), rs2306283 (c.388A>G), rs11045819 (c.463C>A), rs4363657 (g.89595T>C)] were analyzed. A statistically significant association was found between the LDL-C-lowering effectiveness and the rs4149056 and rs11045819 in the heterozygote model; and the rs4149056, rs2306283, and rs11045819 in the homozygote model. In the subgroup analyses, non-Asian populations, simvastatin, and pravastatin showed significant associations between LDL-C-lowering efficacy and the rs4149056 or rs2306283. Significant associations between the rs2306283 and HDL-C-increasing effectiveness were found in the homozygote model. Regarding TC-reducing, significant associations were observed in the heterozygote and homozygote models of the rs11045819. There was no heterogeneity and publication bias among most studies. CONCLUSION: SLCO1B1 variants can be used as signals to predict the statins' effectiveness.

A Listeria-based vaccine targeting ISG15 exerts anti-tumor efficacy in renal cell carcinoma.

Renal cell carcinoma (RCC) is the deadliest form of urological cancer and is projected to be the fourth most common neoplasm in the USA in males by 2040. In addition to the current poor prognosis with 5-year survival rates hardly reaching 15%, the prevalence of resistance to currently available systemic therapies has also established an urgent need to develop new treatment regimen(s) for advanced RCC. Interferon-stimulated gene 15 (ISG15) is the first identified ubiquitin-like modifier and has been intensively studied for its central role in innate immunity against intracellular pathogens. However, in this study, we identified ISG15 as a novel tumor-associated antigen and prognostic marker in RCC. Further, we therapeutically targeted elevated ISG15 expression by means of a Listeria monocytogenes (Lm)-based vaccine, designated Lm-LLO-ISG15, in both subcutaneous and orthotopic RCC mouse models. Treatment with Lm-LLO-ISG15 resulted in an influx of tumor-infiltrating effector T cells and significant anti-tumor efficacy in both subcutaneous and orthotopic RCC tumor models. Treatment with Lm-LLO-ISG15 also generated a robust interferon-gamma response and attracted a larger pool of polyfunctional T cells into the tumor microenvironment. Importantly, the therapeutic efficacy of Lm-LLO-ISG15 in RCC is comparable to that of anti-PD-1 and sunitinib, the current frontline therapies for RCC patients. Collectively, our work illustrates that targeting ISG15 in RCC with a CTL-based immunotherapy such as Lm-LLO-ISG15 is a promising and potentially translatable therapeutic strategy to enhance survival in RCC patients.

Tumoral CD105 promotes immunosuppression, metastasis, and angiogenesis in renal cell carcinoma.

CD105 (endoglin) is a transmembrane protein that functions as a TGF-beta coreceptor and is highly expressed on endothelial cells. Unsurprisingly, preclinical and clinical evidence strongly suggests that CD105 is an important contributor to tumor angiogenesis and tumor progression. Emerging evidence suggests that CD105 is also expressed by tumor cells themselves in certain cancers such as renal cell carcinoma (RCC). In human RCC tumor cells, CD105 expression is associated with stem cell-like properties and contributes to the malignant phenotype in vitro and in xenograft models. However, as a regulator of TGF-beta signaling, there is a striking lack of evidence for the role of tumor-expressed CD105 in the anti-tumor immune response and the tumor microenvironment. In this study, we report that tumor cell-expressed CD105 potentiates both the in vitro and in vivo tumorigenic potential of RCC in a syngeneic murine RCC tumor model. Importantly, we find that tumor cell-expressed CD105 sculpts the tumor microenvironment by enhancing the recruitment of immunosuppressive cell types and inhibiting the polyfunctionality of tumor-infiltrating CD4+ and CD8+ T cells. Finally, while CD105 expression by endothelial cells is a well-established contributor to tumor angiogenesis, we also find that tumor cell-expressed CD105 significantly contributes to tumor angiogenesis in RCC.

Chloride Channel-3 (ClC-3) Modifies the Trafficking of Leucine-Rich Repeat-Containing 8A (LRRC8A) Anion Channels.

Chloride channel-3 (ClC-3) Cl-/H+ antiporters and leucine-rich repeat-containing 8 (LRRC8) family anion channels have both been associated with volume-regulated anion currents (VRACs). VRACs are often altered in ClC-3 null cells but are absent in LRRC8A null cells. To explore the relationship between ClC-3, LRRC8A, and VRAC we localized tagged proteins in human epithelial kidney (HEK293) cells using multimodal microscopy. Expression of ClC-3-GFP induced large multivesicular bodies (MVBs) with ClC-3 in the delimiting membrane. LRRC8A-RFP localized to the plasma membrane and to small cytoplasmic vesicles. Co-expression demonstrated co-localization in small, highly mobile cytoplasmic vesicles that associated with the early endosomal marker Rab5A. However, most of the small LRRC8A-positive vesicles were constrained within large MVBs with abundant ClC-3 in the delimiting membrane. Dominant negative (S34A) Rab5A prevented ClC-3 overexpression from creating enlarged MVBs, while constitutively active (Q79L) Rab5A enhanced this phenotype. Thus, ClC-3 and LRRC8A are endocytosed together but independently sorted in Rab5A MVBs. Subsequently, LRRC8A-labeled vesicles were sorted to MVBs labeled by Rab27A and B exosomal compartment markers, but not to Rab11 recycling endosomes. VRAC currents were significantly larger in ClC-3 null HEK293 cells. This work demonstrates dependence of LRRC8A trafficking on ClC-3 which may explain the association between ClC-3 and VRACs.

SCRINSHOT enables spatial mapping of cell states in tissue sections with single-cell resolution.

Changes in cell identities and positions underlie tissue development and disease progression. Although single-cell mRNA sequencing (scRNA-Seq) methods rapidly generate extensive lists of cell states, spatially resolved single-cell mapping presents a challenging task. We developed SCRINSHOT (Single-Cell Resolution IN Situ Hybridization On Tissues), a sensitive, multiplex RNA mapping approach. Direct hybridization of padlock probes on mRNA is followed by circularization with SplintR ligase and rolling circle amplification (RCA) of the hybridized padlock probes. Sequential detection of RCA-products using fluorophore-labeled oligonucleotides profiles thousands of cells in tissue sections. We evaluated SCRINSHOT specificity and sensitivity on murine and human organs. SCRINSHOT quantification of marker gene expression shows high correlation with published scRNA-Seq data over a broad range of gene expression levels. We demonstrate the utility of SCRINSHOT by mapping the locations of abundant and rare cell types along the murine airways. The amenability, multiplexity, and quantitative qualities of SCRINSHOT facilitate single-cell mRNA profiling of cell-state alterations in tissues under a variety of native and experimental conditions.

Emerging waste-to-wealth applications of fly ash for environmental remediation: A review.

The considerable increase in world energy consumption owing to rising global population, intercontinental transportation and industrialization has posed numerous environmental concerns. Particularly, in order to meet the required electricity supply, thermal power plants for electricity generation are widely used in many countries. However, an annually excessive quantity of waste fly ash up to 1 billion tones was globally discarded from the combustion of various carbon-containing feedstocks in thermoelectricity plants. About half of the industrially generated fly ash is dumped into landfills and hence causing soil and water contamination. Nonetheless, fly ash still contains many valuable components and possesses outstanding physicochemical properties. Utilizing waste fly ash for producing value-added products has gained significant interests. Therefore, in this work, we reviewed the current implementation of fly ash-derived materials, namely, zeolite and geopolymer as efficient adsorbents for the environmental treatment of flue gas and polluted water. Additionally, the usage of fly ash as a catalyst support for the photodegradation of organic pollutants and reforming processes for the corresponding wastewater remediation and H2 energy generation is thoroughly covered. In comparison with conventional carbon-based adsorbents, fly ash-derived geopolymer and zeolite materials reportedly exhibited greater heavy metal ions removal and reached the maximum adsorption capacity of about 150 mg g-1. As a support for biogas reforming process, fly ash could enhance the activity of Ni catalyst with 96% and 97% of CO2 and CH4 conversions, respectively.

Telepharmacy: A Systematic Review of Field Application, Benefits, Limitations, and Applicability During the COVID-19 Pandemic.

Introduction: Telepharmacy is widely known as the delivery of pharmacy care offered by registered pharmacists and pharmacies using telecommunication technologies to patients at a distance. We conducted a systematic review of the reported usages, benefits, and limitations of telepharmacy models worldwide to further clarify the pros and cons of a telepharmacy model. Methods: A total of 39 relevant articles was included after searching for articles with a fixed term on four databases, including PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of April 2021. Results: Our review suggested that telepharmacy has played an essential role in addressing pharmacist shortages and helping patients both safely and effectively administer medications in underserved areas. During the COVID-19 pandemic, remote dispensing and counseling are effective measures to avoid infection. Conclusion: Telepharmacy could potentially replace or complement pharmaceutical-related activities, facilitating future innovation in the health care industry.

The Efficiency of Neurospheres Derived from Human Wharton's Jelly Mesenchymal Stem Cells for Spinal Cord Injury Regeneration in Rats.

Spinal cord injury (SCI) causes inflammation and neuronal degeneration, resulting in functional movement loss. Since the availability of SCI treatments is still limited, stem cell therapy is an alternative clinical treatment for SCI and neurodegenerative disorders. Human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) are an excellent option for cell therapy. This study aimed to induce hWJ-MSCs into neural stem/progenitor cells in sphere formation (neurospheres) by using neurogenesis-enhancing small molecules (P7C3 and Isx9) and transplant to recover an SCI in a rat model. Inducted neurospheres were characterized by immunocytochemistry (ICC) and gene expression analysis. The best condition group was selected for transplantation. The results showed that the neurospheres induced by 10 µM Isx9 for 7 days produced neural stem/progenitor cell markers such as Nestin and ß-tubulin 3 through the Wnt3A signaling pathway regulation markers (ß-catenin and NeuroD1 gene expression). The neurospheres from the 7-day Isx9 group were selected to be transplanted into 9-day-old SCI rats. Eight weeks after transplantation, rats transplanted with the neurospheres could move normally, as shown by behavioral tests. MSCs and neurosphere cells were detected in the injured spinal cord tissue and produced neurotransmitter activity. Neurosphere-transplanted rats showed the lowest cavity size of the SCI tissue resulting from the injury recovery mechanism. In conclusion, hWJ-MSCs could differentiate into neurospheres using 10 µM Isx9 media through the Wnt3A signaling pathway. The locomotion and tissue recovery of the SCI rats with neurosphere transplantation were better than those without transplantation.