Novel protein-truncating variants of a chromatin-modifying gene MSL2 in syndromic neurodevelopmental disorders.

Numerous large scale genomic studies have uncovered rare but recurrent pathogenetic variants in a significant number of genes encoding epigenetic machinery in cases with neurodevelopmental disorders (NDD) especially autism spectrum disorder (ASD). These findings provide strong support for the functional importance of epigenetic regulators in neurodevelopment. After the clinical genomics evaluation of the patients using exome sequencing, we have identified, three novel protein-truncating variants (PTVs) in the MSL2 gene (OMIM: 614802) which encodes a chromatin modifying enzyme. MSL2 modifies chromatin through both mono-ubiquitination of histone 2B on lysine 34 (K34) and acetylation of histone H4 on lysine 16 (K16). We reported first time the detailed clinical features associated with 3 MSL2 PTVs. There are 15 PTVs (13 de novo) reported from the large genomics studies (12 cases) or ClinVar (3 cases) of NDD, ASD, and developmental disorders (DD) but the specific clinical features for these cases are not described. Taken together, our descriptions of dysmorphic face and other features support the causal role of MSL2 in a likely syndromic neurodevelopmental disorder and add MSL2 to a growing list of epigenetic genes implicated in ASD.

Enhanced efficiency of AgAlO2/g-C3N4 binary composite to degrade organic pollutants for environmental remediation under visible light irradiation.

This study explores the utilization of semiconductor-based photocatalysts for environmental remediation through photocatalytic degradation, harnessing solar energy for effective treatment. The primary focus is on the application of photocatalytic technology for the degradation of 2-chlorophenol and methylene blue, critical pollutants requiring remediation. The research involves the synthesis of binary AgAlO2/g-C3N4 nanocomposites through an exchange ion method, subsequent calcination, and sonication. This process enhances the transfer of photogenerated electrons from AgAlO2 to g-C3N4, resulting in a significantly increased reductive electron charge on the surface of g-C3N4. The photocatalytic activity of the synthesized composites is comprehensively examined in the degradation of 2-chlorophenol and methylene blue through detailed crystallographic, electron-microscopy, photoemission spectroscopy, electrochemical, and spectroscopic characterizations. Among the various composites, AgAlO2/20% g-C3N4 emerges as the most active photocatalyst, achieving an impressive 98% degradation of methylene blue and 97% degradation of 2-chlorophenol under visible light. Notably, AgAlO2/20% g-C3N4 surpasses bare AgAlO2 and bare g-C3N4, exhibiting 1.66 times greater methylene blue degradation and constant rate (k) values of 20.17 × 10-3 min-1, 4.18 × 10-3 min-1 and 3.48 × 10-3 min-1, respectively. The heightened photocatalytic activity is attributed to the diminished recombination rate of electron-hole pairs. Scavenging evaluations confirm that O2•- and h+ are the primary photoactive species steering methylene blue photodegradation over AgAlO2/g-C3N4 in the visible region. These findings present new possibilities for the development of efficient binary photocatalysts for environmental remediation.

Stably suspended SiO2-supported CdS photocatalyst for a promising organic pollutant degradation in the absence of mechanical stirring.

Even with solar-activatable photocatalyst, incommensurable energy input for stirring is still required to overcome the transport limitations in powder-photocatalysis. To counter this, a novel concept of auto-suspending photocatalyst based on SiO2/CdS was proposed to enable promising photo-activity even under stirring-free condition. Functionally-speaking, CdS would act as photoreaction-driver while SiO2 endows sufficient buoyance for suspension-stabilization during stirring-free photocatalysis. In photoreactions degrading methylene blue for theoretical demonstration, SiO2/CdS_0.3 promises only 4.57% activity reduction in non-stirred photoreaction, enabling 15.26% of methylene blue decolorization comparing to 15.99% of stirred-photoreaction under visible light irradiation. This could be ascribed to the slow settling tendency of SiO2/CdS_0.3, evading severe light-shielding under stacked condition. Also, its rightly-exposed SiO2 surface permits 'adsorb-and-degrade' mechanism, thereby overcoming the sluggish surface transport across thick boundary layer. Contrarily, photocatalyst with quintuple CdS content (SiO2/CdS_1.5) exhibits largest activity reduction (31.47%), reasoned by its quick-settling tendency. Overall, current study provides new perspectives to photocatalysis-community. The success elimination of mechanical stirring from photocatalysis promises significant energy-saving (19.1-136 kW/m3), thus consenting better practicality for solar energy-harvesting and environmental protection.

Long-term evaluation of palm oil mill effluent (POME) steam reforming over lanthanum-based perovskite oxides.

To replace the obsolete ponding system, palm oil mill effluent (POME) steam reforming (SR) over net-acidic LaNiO3 and net-basic LaCoO3 were proposed as the POME primary treatments, with promising H2-rich syngas production. Herein, the long-term evaluation of POME SR was scrutinized with both catalysts under the optimal conditions (600 °C, 0.09 mL POME/min, 0.3 g catalyst, & 74-105 µm catalyst particle size) to examine the catalyst microstructure changes, transient process stability, and final effluent evaluation. Extensive characterization proved the (i) adsorption of POME vapour on catalysts before SR, (ii) deposition of carbon and minerals on spent SR catalysts, and (iii) dominance of coking deactivation over sintering deactivation at 600 °C. Despite its longer run, spent LaCoO3 (50.54 wt%) had similar carbon deposition with spent LaNiO3 (50.44 wt%), concurring with its excellent coke resistance. Spent LaCoO3 (6.12 wt%; large protruding crystals) suffered a harsher mineral deposition than spent LaNiO3 (3.71 wt%; thin film coating), confirming that lower reactivity increased residence time of reactants. Transient syngas evolution of both SR catalysts was relatively steady up to 4 h but perturbed by coking deactivation thereafter. La2O2CO3 acted as an intermediate species that hastened the coke removal via reverse Boudouard reaction upon its decarbonation. La2O2CO3 decarbonation occurred continuously in LaCoO3 system but intermittently in LaNiO3 system. LaNiO3 system only lasted for 13 h as its compact ash blocked the gas flow. LaCoO3 system lasted longer (17 h) with its porous ash, but it eventually failed because KCl crystallites blocked its active sites. Relatively, LaCoO3 system offered greater net H2 production (72.78%) and POME treatment volume (30.77%) than LaNiO3 system. SR could attain appreciable POME degradation (>97% COD, BOD5, TSS, & colour intensity). Withal, SR-treated POME should be polished to further reduce its incompliant COD and BOD5.

Instant Formulation of Inhalable Beclomethasone Dipropionate-Gamma-Cyclodextrin Composite Particles Produced Using Supercritical Assisted Atomization.

Medical composites derived from Gamma-cyclodextrin (γ-CD) and beclomethasone dipropionate-gamma-cyclodextrin (BDP-γ-CD) are synthesized over supercritical-assisted atomization (SAA) herein. Carbon dioxide, which serves the dual function of spraying medium and co-solute, is incorporated in this process along with the ethanolic solvent. Results indicate that, for fine spherical particles, optimized aerosol performance could be obtained with 50.0% (w/w) ethanolic solvent, precipitator, and saturator at 373.2 K and 353.2 K, respectively, and carbon dioxide-to-γ-CD flow ratio of 1.8 in the presence of 10 wt% leucine (LEU) as dispersion enhancer. It is also noted that γ-CD solution at low concentration typically renders better aerosol performance of the particles. During drug particle-derivation, the solubility of drug BDP elevated considerably due to the formation of inclusion complexes, further assisted by the ethanolic solvent which increases the lipophilicity of BDP. Meanwhile, the in vitro aerosolization and dissolution performance of drug composites derived from varied γ-CD-to-BDP mass ratio (Z) were also evaluated. It was found that high Z promises higher fine particle fraction in the obtained drug composite while the dissolution rate of active ingredient (BDP) exhibits positive correlation to the content of water-soluble excipient (γ-CD) in the formulation. This study offers a new avenue for instant drug formulation with promising pulmonary delivery over the SAA technique.

Comparative subgenomic mRNA profiles of SARS-CoV-2 Alpha, Delta and Omicron BA.1, BA.2 and BA.5 sub-lineages using Danish COVID-19 genomic surveillance data.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread worldwide in the population since it was first detected in late 2019. The transcription and replication of coronaviruses, although not fully understood, is characterised by the production of genomic length RNA and shorter subgenomic RNAs to make viral proteins and ultimately progeny virions. Observed levels of subgenomic RNAs differ between sub-lineages and open reading frames but their biological significance is presently unclear. METHODS: Using a large and diverse panel of virus sequencing data produced as part of the Danish COVID-19 routine surveillance together with information in electronic health registries, we assessed the association of subgenomic RNA levels with demographic and clinical variables of the infected individuals. FINDINGS: Our findings suggest no significant statistical relationship between levels of subgenomic RNAs and host-related factors. INTERPRETATION: Differences between lineages and subgenomic ORFs may be related to differences in target cell tropism, early virus replication/transcription kinetics or sequence features. FUNDING: The author(s) received no specific funding for this work.

Innovative solid desiccant dehumidification using distributed microwaves.

Dehumidification is one of the key challenges facing the air conditioning (AC) industry in the treatment of moist air. Over many decades, the dual role of heat exchangers of AC chillers for the sensible and latent cooling of space has hindered the thermal-lift reduction in the refrigeration cycle due to the requirements of water vapor removal at dew-point and heat rejection to the ambient air. These practical constraints of AC chillers have resulted in the leveling of energy efficiency of mechanical vapor compressors (MVC) for many decades. One promising approach to energy efficiency improvement is the decoupling of dehumidification from sensible processes so that innovative but separate processes can be applied. In this paper, an advanced microwave dehumidification method is investigated in the laboratory, where the microwave (2.45 GHz) energy can be irradiated onto the dipole structure of water vapor molecules, desorbing rapidly from the pores of adsorbent. Results show a significant improvement in performance for microwave dehumidification, up to fourfold, as compared to data available in the literature.

Percutaneous left atrial appendage occlusion following successful treatment of large bi-atrial thrombi in a patient with atrial fibrillation: a case report.

Background: Atrial fibrillation (AF) is a well-established risk factor for intracardiac thrombosis. Left atrial appendage occlusion (LAAO) is emerging as a viable alternative to oral anticoagulation (OAC) for high-risk AF patients who are contraindicated to long-term OAC. Case summary: A 74-year-old man with a history of permanent AF and subdural haemorrhage on warfarin therapy was referred to our facility for further management. Cardiac CT imaging revealed large bi-atrial thrombi for which apixaban therapy was initiated. Serial imaging over nine months showed gradual shrinkage and then resolution of the thrombi. In line with the patient's preference to avoid life-long OAC, he received LAAO using an Amplatzer™ Amulet™ device. Follow-up transoesophageal echocardiography showed a well-seated device with no leak and no thrombus. Discussion: We discussed the key issues surrounding management of bi-atrial thrombi and the decision to perform LAAO in these circumstances, relying on shared decision making and multi-disciplinary team input.

Surveillance, isolation and genomic characterization of Pteropine orthoreovirus of probable bat origin among patients with acute respiratory infection in Malaysia.

Pteropine orthoreovirus (PRV), an emerging bat-borne virus, has been linked to cases of acute respiratory infections (ARI) in humans. The prevalence, epidemiology and genomic diversity of PRV among ARI of unknown origin were studied. Among 632 urban outpatients tested negative for all known respiratory viruses, 2.2% were PRV-positive. Patients mainly presented with moderate to severe forms of cough, sore throat and muscle ache, but rarely with fever. Phylogenetic analysis revealed that over 90% of patients infected with the Melaka virus (MelV)-like PRV, while one patient infected with the Pulau virus previously found only in fruit bats. Human oral keratinocytes and nasopharyngeal epithelial cells were susceptible to clinical isolates of PRV, including the newly isolated MelV-like 12MYKLU1034. Whole genome sequence of 12MYKLU1034 using Nanopore technique revealed a novel reassortant strain. Evolutionary analysis of the global PRV strains suggests the continuous evolution of PRV through genetic reassortment among PRV strains circulating in human, bats and non-human primate hosts, creating a spectrum of reassortant lineages with complex evolutionary characteristics. In summary, the role of PRV as a common etiologic agent of ARI is evident. Continuous monitoring of PRV prevalence, pathogenicity and diversity among human and animal hosts is important to trace the emergence of novel reassortants.

Work Outcomes and Medical Costs Among Singaporean Adolescent and Young Adult Cancer Survivors.

Purpose: To quantify and evaluate trends of work outcomes and medical costs among Singaporean adolescent and young adult (AYA) cancer survivors. Methods: This cross-sectional study was conducted at the National Cancer Centre Singapore between July 2016 and October 2018. Cancer patients who were diagnosed between the age of 15 and 39 years and had completed treatment were eligible. Siblings of cancer patients were recruited as controls. Work outcomes were collected using an investigator-designed questionnaire, while cost data were extracted from the hospital database. Descriptive statistics were used to quantify work and cost outcomes. Mixed-effects logistic regression was used to compare employment rates between survivors and controls. Generalized linear models were used to characterize trends between medical costs and symptom burden. Results: A total of 29 cancer survivors and 23 sibling controls were analyzed. Approximately 80% of survivors and controls were employed at the time of survey; however, more than half of the employed survivors reported impaired work outcomes due to effects from cancer and cancer treatment, including work reallocation, absenteeism, and decreased work ability. Median productivity loss due to absenteeism in the past 3 months was estimated to be U.S. dollar (USD) 110. Total medical cost incurred within the first year after treatment completion remained high at a median of USD6592, with out-of-pocket expenditure between 17.2% and 100.0%. Conclusion: Despite their young age and having completed cancer treatment, Singaporean AYA cancer survivors may continue to experience poor work outcomes even after resuming work. High medical costs may also persist.

Endogenous GLP-1 levels play an important role in determining the efficacy of DPP-IV Inhibitors in both prediabetes and type 2 diabetes.

Background: In contrast to Western population, glucagon-like peptide-1 (GLP-1) levels are preserved in some East Asian population with type 2 diabetes (T2D), explaining why dipeptidyl peptidase-IV (DPP-IV) inhibitors are more effective in East Asians. We assessed whether differences in endogenous GLP-1 levels resulted in different treatment responses to DPP-IV inhibitors in prediabetes and T2D. Methods: A prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices. Results: There was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol/L), 2-hour glucose post-OGTT (-2.4 mmol/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported. Conclusions: Linagliptin resulted in a greater HbA1c reduction in the high GLP-1 prediabetes and T2D compared to low GLP-1 groups. Endogenous GLP-1 level play an important role in determining the efficacy of DPP-IV inhibitors irrespective of the abnormal glucose tolerance states.

Fasting and stimulated glucagon-like peptide-1 exhibit a compensatory adaptive response in diabetes and pre-diabetes states: A multi-ethnic comparative study.

Background: Impaired secretion of glucagon-like peptide-1 (GLP-1) among Caucasians contributes to reduced incretin effect in type 2 diabetes mellitus (T2DM) patients. However, studies emanating from East Asia suggested preserved GLP-1 levels in pre-diabetes (pre-DM) and T2DM. We aimed to resolve these conflicting findings by investigating GLP-1 levels during oral glucose tolerance test (OGTT) among Malay, Chinese, and Indian ethnicities with normal glucose tolerance (NGT), pre-DM, and T2DM. The association between total GLP-1 levels, insulin resistance, and insulin sensitivity, and GLP-1 predictors were also analyzed. Methods: A total of 174 subjects were divided into NGT (n=58), pre-DM (n=54), and T2DM (n=62). Plasma total GLP-1 concentrations were measured at 0, 30, and 120 min during a 75-g OGTT. Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of insulin sensitivity (HOMA-IS), and triglyceride-glucose index (TyG) were calculated. Results: Total GLP-1 levels at fasting and 30 min were significantly higher in T2DM compared with pre-DM and NGT (27.18 ± 11.56 pmol/L vs. 21.99 ± 10.16 pmol/L vs. 16.24 ± 7.79 pmol/L, p=0.001; and 50.22 ± 18.03 pmol/L vs. 41.05 ± 17.68 pmol/L vs. 31.44 ± 22.59 pmol/L, p<0.001; respectively). Ethnicity was a significant determinant of AUCGLP-1, with the Indians exhibiting higher GLP-1 responses than Chinese and Malays. Indians were the most insulin resistant, whereas Chinese were the most insulin sensitive. The GLP-1 levels were positively correlated with HOMA-IR and TyG but negatively correlated with HOMA-IS. This relationship was evident among Indians who exhibited augmented GLP-1 responses proportionately to their high insulin-resistant states. Conclusion: This is the first study that showed GLP-1 responses are augmented as IR states increase. Fasting and post-OGTT GLP-1 levels are raised in T2DM and pre-DM compared to that in NGT. This raises a possibility of an adaptive compensatory response that has not been reported before. Among the three ethnic groups, the Indians has the highest IR and GLP-1 levels supporting the notion of an adaptive compensatory secretion of GLP-1.

Cross-redox and simultaneous removal of Cr(VI) and As(III): Influences of Fe(II), Fe(III), oxalic acid, and dissolved organic carbon.

Hexavalent chromium [Cr(VI)] and arsenite [As(III)] are hazardous to both human and ecosystem. While their cross-redox reaction decreases both their toxicities, the interferences from ubiquitous substances like Fe (Fe(II) and Fe(III)) and organic compounds (oxalic acid and soil-extracted dissolved organic carbon (DOC)) on such interaction are rarely reported; thence, inspires the investigation in this study. Results showed that the cross-redox, in the absence of interfering substances, only occurred at pH≤2.0, with reaction orders of 0.676 and 0.783 in respect to the concentration of Cr(VI) and As(III). The pseudo-reaction constant, k', of such reaction was recorded at 0.087 m1.377/(mmol0.459 min). With the addition of Fe(II), the rate of Cr(VI) reduction is promoted in conjunction with suppressed As(III) oxidation. Upon neutralizing to pH 6.0, such reduced Cr can be entirely removed via Fe(II)-assisted adsorption and/or co-precipitation. Meanwhile, the elimination of aqueous As is relatively inferior (36 %), attributed to the largely preserved As(III), which is less susceptible to adsorptive/co-precipitative removal. Unlike Fe(II), Fe(III) did not alter Cr(VI)-As(III) cross-redox path, but triggered high adsorptive and/or co-precipitative removals of Cr and As (90 %). In contrast, both organically-altered systems exhibits plummeted As(III) oxidation, under distinctive mechanisms: oxalic acid competes with As(III) in the redox interactions while DOC reduces As(V) into As(III). Also, DOC would undergo complexion with metals and/or blocked the adsorption or co-precipitation sites, leading to even lower Cr and As precipitation. This study unravelled the interference from ubiquitous species in the co-removal of Cr(VI) and As(III), which provides insightful remediation for heavy metal contaminations.

Hydrothermal synthesis temperature induces sponge-like loose silica structure: A potential support for Fe2O3-based adsorbent in treating As(V)-contaminated water.

Low cost Fe2O3-based sorbents with an exceptional selectivity toward the targeted As(V) pollutant have gained extensive attention in water treatment. However, their structural features often influence removal performance. In this respect, we present herein a rational design of silica-supported Fe2O3 sorbents with an enhanced morphological structure based on a simple temperature-induced process. Low-hydrothermal temperature synthesis (60 and 100 °C) provided a large silica-cluster size with a close packed structure (S-60 and S-100), contributing to an increase in mass transport resistance. Fe2O3/S-60 with 6.2-nm pore width silica achieved a maximum As(V) uptake capacity (qm) of only 3.5 mg g-1. Supporting Fe2O3 on S-100 with an approximately two-fold increase in the pore size (13 nm) did not lead to any evident enhancement in qe (3.7 mg g-1). However, expanding the pore window up to 22.6 nm (S-140) and 39.5 nm (S-180), along with changing from close-packed to sponge-like loose structures induced by high-temperature synthesis (140 °C and 180 °C), resulted in substantial increases in qm. Fe2O3/S-140 had 1.7 and 1.6 times higher qm (5.9 mg g-1) than Fe2O3/S-100 and Fe2O3/S-60, respectively. The highest qm (7.4 mg g-1) was achieved for Fe2O3/S-180, which was attributed to its relatively small-sized silica cluster and the largest cavities that facilitated easier access by As(V) to adsorbing sites.

Flexible and Highly Conductive Textiles Induced by Click Chemistry for Sensitive Motion and Humidity Monitoring.

To date, multifunctional sensors have aroused widespread concerns owing to their vital roles in the healthcare area. However, there are still significant challenges in the fabrication of functionalized integrated devices. In this work, hydrophobic-hydrophilic patterns are constructed on polyester-spandex-blended knitted fabric surface by the chemical click method, enabling accurate deposition of functionalized materials for sensitive and stable motion and humidity sensing. Representatively, a conductive silver nanowire (Ag NW) network was deliberately deposited on only the designated hydrophilic fabric surface to realize accurate, repeatable, and stable motion sensing. Such a Ag NWs sensor recorded a low electrical resistance (below 60 Ω), stable resistance cycling response (over 2000 cycles), and fast response time to humidity (0.46 s) during the sensing evaluation. In addition to experimental sensing, real human motions, such as mouth-opening and joint-flexing (wrist and neck), could also be detected using the same sensor. Similar promising outputs were also obtained over the humidity sensor fabricated over the same chemical click method, except the sensing material was replaced with polydopamine-modified carboxylated carbon nanotubes. The resultant sensor exhibits excellent sensitivity to not only experimentally adjusted environment humidity but also to the moisture content of breath and skin during daily activities. On top of all these, both sensors were fabricated over highly flexible fabric that offers high wearability, promising great application potential in the field of healthcare monitoring.

Facile preparation of tremella-like TiO2/Cd:ZnIn2S4 photoanode with enhanced photo-electro-chemical (PEC) performance for energy and environmental applications.

The realization of solar-driven photoelectrochemical (PEC) process lies in the success development of materials with excellent photoelectric properties. Past reports identified TiO2, upon modified with both Cd and ZnIn2S4 (ZIS), exhibits promising PEC performance; however, at the cost of tedious preparation. In view of this, our work proposes a facile one-step hydrothermal strategy to deposit both modifiers onto the pre-obtained TiO2 nanotubes (NTs), realizing rose-like TiO2/ZnIn2S4 (TiO2/ZIS) or tremella-like TiO2/Cd:ZnIn2S4 (TiO2/Cd:ZIS) with improved PEC performances. Interestingly, the thickness of ZIS petals, which deposited on top of TiO2 NTs, is positively-correlated to its Cd-composition, signifying the substitutional doping of Cd into the unit cell of ZIS. This renders robust ionic interactions between the constituents, prompting the enhanced optical properties of TiO2 in conjecture to its reduced impedance. As a result, the recombination rate of photo-electric-derived carriers was drastically suppressed, with an improved photocurrent density of 606.2 µA cm-2 recorded by TiO2/Cd:ZIS photoanode under solar irradiation. Such performance is 80 times and 5.16 times higher than those of bare TiO2 NTs and TiO2/ZIS counterparts. The photoconversion efficiencies in terms of incident photon-to-current conversion efficiency (IPCE) and applied bias photon current efficiency (ABPE) for TiO2/Cd:ZIS were significantly improved too, recorded at 1.12% and 0.38%, respectively, under standard evaluation condition. As summary, our work proposes a facile one-step hydrothermal approach that simultaneously-deposit both Cd and ZIS onto TiO2 photoanode for an enhanced PEC performance. This opens up a wider horizon for PEC technology, further unlocking its potential in both energy and environmental applications.

The IDentif.AI-x pandemic readiness platform: Rapid prioritization of optimized COVID-19 combination therapy regimens.

IDentif.AI-x, a clinically actionable artificial intelligence platform, was used to rapidly pinpoint and prioritize optimal combination therapies against COVID-19 by pairing a prospective, experimental validation of multi-drug efficacy on a SARS-CoV-2 live virus and Vero E6 assay with a quadratic optimization workflow. A starting pool of 12 candidate drugs developed in collaboration with a community of infectious disease clinicians was first narrowed down to a six-drug pool and then interrogated in 50 combination regimens at three dosing levels per drug, representing 729 possible combinations. IDentif.AI-x revealed EIDD-1931 to be a strong candidate upon which multiple drug combinations can be derived, and pinpointed a number of clinically actionable drug interactions, which were further reconfirmed in SARS-CoV-2 variants B.1.351 (Beta) and B.1.617.2 (Delta). IDentif.AI-x prioritized promising drug combinations for clinical translation and can be immediately adjusted and re-executed with a new pool of promising therapies in an actionable path towards rapidly optimizing combination therapy following pandemic emergence.

Application of a VP4/VP2-inferred transmission clusters in estimating the impact of interventions on rhinovirus transmission.

BACKGROUND: Despite the clinical burden attributable to rhinovirus (RV) infections, the RV transmission dynamics and the impact of interventions on viral transmission remain elusive. METHODS: A total of 3,935 nasopharyngeal specimens were examined, from which the VP4/VP2 gene was sequenced and genotyped. RV transmission clusters were reconstructed using the genetic threshold of 0.005 substitutions/site, estimated from the global VP4/VP2 sequences. A transmission cluster is characterized by the presence of at least two individuals (represent by nodes), whose viral sequences are genetically linked (represent by undirected edges) at the estimated genetic distance threshold supported by bootstrap value of ≥ 90%. To assess the impact of facemask, pleconaril and social distancing on RV transmission clusters, trials were simulated for interventions with varying efficacy and were evaluated based on the reduction in the number of infected patients (nodes) and the reduction in the number of nodes-connecting edges. The putative impact of intervention strategies on RV transmission clusters was evaluated through 10,000 simulations. RESULTS: A substantial clustering of 168 RV transmission clusters of varying sizes were observed. This suggests that RV disease burden observed in the population was largely due to multiple sub-epidemics, predominantly driven by RV-A, followed by RV-C and -B. No misclassification of RV species and types were observed, suggesting the specificity and sensitivity of the analysis. Through 10,000 simulations, it was shown that social distancing may be effective in decelerating RV transmission, by removing more than 95% of nodes and edges within the RV transmission clusters. However, facemask removed less than 8% and 66% of nodes and edges, respectively, conferring moderate advantage in limiting RV transmission. CONCLUSION: Here, we presented a network-based approach of which the degree of RV spread that fuel disease transmission in the region was mapped for the first time. The utilization of RV transmission clusters in assessing the putative impact of interventions on disease transmission at the population level was demonstrated.

Microbial fuel cells for bioelectricity production from waste as sustainable prospect of future energy sector.

Microbial fuel cell (MFC) is lauded for its potentials to solve both energy crisis and environmental pollution. Technologically, it offers the capability to harness electricity from the chemical energy stored in the organic substrate with no intermediate steps, thereby minimizes the entropic loss due to the inter-conversion of energy. The sciences underneath such MFCs include the electron and proton generation from the metabolic decomposition of the substrate by microbes at the anode, followed by the shuttling of these charges to cathode for electricity generation. While its promising prospects were mutually evinced in the past investigations, the upscaling of MFC in sustaining global energy demands and waste treatments is yet to be put into practice. In this context, the current review summarizes the important knowledge and applications of MFCs, concurrently identifies the technological bottlenecks that restricted its vast implementation. In addition, economic analysis was also performed to provide multiangle perspectives to readers. Succinctly, MFCs are mainly hindered by the slow metabolic kinetics, sluggish transfer of charged particles, and low economic competitiveness when compared to conventional technologies. From these hindering factors, insightful strategies for improved practicality of MFCs were formulated, with potential future research direction being identified too. With proper planning, we are delighted to see the industrialization of MFCs in the near future, which would benefit the entire human race with cleaner energy and the environment.

Biomass-derived carbon-based and silica-based materials for catalytic and adsorptive applications- An update since 2010.

Biomass, which defined as plant- or animal-based materials, is intriguing tremendous scientific attentions due to its renewable attribute in serving energy security. Amongst, the plant-based biomasses, particularly those that co-generated in the agriculture activities, are commonly regarded as fuel for burning, which overlooked their hidden potentials for high-end applications. Organically, the plant-based biomass constitutes of lignocellulose components, which can be served as promising precursors for functionalized carbon materials. Meanwhile, its inorganic counterpart made up of various minerals, with Si being the most concerned one. With the advancement of biomass technologies and material synthesis in recent years, numerous attempts were endeavoured to obtain valorised products from biomass. Particularly, syntheses of catalytic and adsorptive materials are actively researched in the field of biomass reutilization. Herein, our work systematically summarized the advancements of biomass-materials for these applications in recent 10 years (2010-2020), with a special focus on the carbon-based and Si-based catalytic/adsorptive materials. Significantly, the deriving steps, inclusive of both pre-treatment and post-treatment of such materials, are incorporated in the discussion, alongside with their significances revealed too. The performance of the as-obtained materials in the respective application is systematically correlated to their physicochemical properties, hence providing valuable insights to the readers. Challenges and promising directions to be explored are raised too at the end of the review, aiming to advocate better-usage of biomass while offering great opportunities to sustain catalysis and adsorption in the industrial scale.