Search

[Display omitted] • PMS activation by CoFe-LDH was improved by compounding with biochar. • Biochar acted as the catalyst carrier and electron mediator. • Reducing functional groups in biochar facilitated Co(III) and Fe(III) reduction. Efficient and low-cost catalysts for peroxymonosulfate (PMS) activation are needed for pollution prevention and environmental remediation. In this work, PMS activation by CoFe layered double hydroxide (CoFe-LDH) was promoted by compositing with biochar (BC). The characterization and catalytic performance of BC, CoFe-LDH, and BC@CoFe-LDH composite (BC-LDH) were investigated. The results indicated that BC could act as a catalyst carrier and electron mediator, which improved the physicochemical properties of CoFe-LDH and promoted the redox cycle of transition metals. The redox-active moieties (RAMs) of BC, especially the reduced functional groups (e.g., phenolic –OH), played an important role in the reduction of Co(III) and Fe(III). Remarkably, benefiting from the synergistic effect between BC and CoFe-LDH, the resulting BC-LDH exhibited excellent catalytic activity and stability for PMS activation. More reactive oxygen species (ROS) were produced in BC-LDH/PMS system. As a result, 100% of dimethyl phthalate (DMP, 10 mg L−1) degradation efficiency was achieved within 60 min in BC-LDH/PMS system, while only 62% in CoFe-LDH/PMS system. The intermediates of DMP degradation were identified and the degradation pathways were proposed. Our findings are expected to provide new insights into the rational design and application of BC materials and transition metals/PMS system for environmental remediation. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB) includes a group of rare gesnodermatoses that result in blistering and erosions of the skin and mucous membranes. Genetically, pathogenic variants in around 20 genes are known to alter the structural and functional integrity of intraepidermal adhesion and dermo-epidermal anchorage, leading to four different types of EB. Here we report the underlying genetic causes of EB phenotypes segregating in seven large consanguineous families, recruited from different regions of Pakistan. Whole exome sequencing, followed by segregation analysis of candidate variants through Sanger sequencing, identified eight pathogenic variants, including three novel (ITGB4: c.1285G>T, and c.3373G>A; PLEC: c.1828A>G) and five previously reported variants (COL7A1: c.6209G>A, and c.1573C>T; FERMT1: c.676insC; LAMA3: c.151insG; LAMB3: c.1705C>T). All identified variants were either absent or had very low frequencies in the control databases. Our in-silico analyses and 3-dimensional (3D) molecular modeling support the deleterious impact of these variants on the encoded proteins. Intriguingly, we report the first case of a recessively inherited form of rare EBS-Ogna associated with a homozygous variant in the PLEC gene. Our study highlights the clinical and genetic diversity of EB in the Pakistani population and expands the mutation spectrum of EB; it could also be useful for prenatal diagnosis and genetic counseling of the affected families. [ABSTRACT FROM AUTHOR]

Melanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Among other pigmentation disorders in humans, albinism is reported to manifest in both syndromic and nonsyndromic forms as well as with varying inheritance patterns. Oculocutaneous albinism (OCA), an autosomal recessive nonsyndromic form of albinism, presents as partial to complete loss of melanin in the skin, hair, and iris. OCA has been known to be caused by pathogenic variants in seven different genes, so far, according to all the currently published population studies. However, the detection rate of alleles causing OCA varies from 50% to 90%. One of the significant challenges of uncovering the pathological variant underlying disease etiology is inter- and intra-familial locus heterogeneity. This problem is especially pertinent in highly inbred populations. As examples of such familial locus heterogeneity, we present nine consanguineous Pakistani families with segregating OCA due to variants in one or two different known albinism-associated genes. All of the identified variants are predicted to be pathogenic, which was corroborated by several in silico algorithms and association with diverse clinical phenotypes. We report an individual affected with OCA carries heterozygous, likely pathogenic variants in TYR and OCA2, raising the question of a possible digenic inheritance. Altogether, our study highlights the significance of exome sequencing for the complete genetic diagnosis of inbred families and provides the ramifications of potential genetic interaction and digenic inheritance of variants in the TYR and OCA2 genes. [ABSTRACT FROM AUTHOR]

The reuse of polymyxin B (PMB) has attracted extensive attention. Although the resistance mechanism to PMB is clear, there are few reports on the regulation mechanisms and effects of clay minerals on bacteria induced by PMB. The focus of this study is to investigate the multidrug resistance, cell morphology and physiological modification of Escherichia coli (E. coli) exposed to PMB in the presence and absence of clay minerals. To be specific, E. coli was cultured serially for 15 days in the increasing concentration of PMB, with or without halloysite or kaolinite. The potential influence mechanisms of halloysite and kaolinite on E. coli was analyzed by proteomics, antibiotic resistance testing, confocal laser scanning microscopy, scanning electron microscopy and Fourier transform infrared. The results showed that kaolinite could obviously promote the growth of bacteria. Moreover, compared with halloysite, kaolinite could stimulate the overexpression of PMB resistance-related proteins ArnA, ArnB and EptA in E. coli exposed to PMB, and promote the synthesis of peptidoglycan and activate glycolysis pathway to produce energy. In contrast, halloysite was able to regulate the production of low molecular weight thiols by E. coli to prevent bacteria from producing excessive reactive oxygen species, activate the oxidative phosphorylation pathway to supply energy for bacterial life activities, and reduce multidrug resistance of E. coli in a variety of ways. These findings are essential for exploring the impacts of clay minerals on the emergence and spread of multi-drug resistant strains in the environment. Image 1 •Both kaolinite and halloysite enhanced the protective barrier of E. coli. •Kaolinite could obviously promote the growth of E. coli. •Halloysite regulated the production of low molecular weight thiols by E. coli. •Halloysite reduced the PhoP and PhoQ proteins expression of E. coli. •Kaolinite promoted the AcrA and AcrB proteins expression of E. coli. [ABSTRACT FROM AUTHOR]

There is an unmet clinical need for eye drop formulations to efficiently treat the diseases of the posterior ocular segment by non-invasive topical administration. Here, we systematically reviewed the literature on ocular penetration enhancers and their ability to transfer drugs to the posterior segment of the eye in experimental studies. Our aim was to assess which penetration enhancer is the most efficient at delivering drugs to the posterior segment of the eye, when topically applied. We conducted a comprehensive search in three electronic databases (Ovid Embase, Ovid MEDLINE, and PubMed) to identify all the relevant manuscripts reported on ocular penetration enhancers based on the PRISMA guidelines. We identified 6540 records from our primary database search and filtered them per our inclusion/exclusion criteria to select a final list of 14 articles for qualitative synthesis. Of these, 11 studies used cell penetrating peptides (CPPs), 2 used chitosan, and 1 used benzalkonium chloride (BAC) as the penetration enhancer. Cationic and amphipathic CPPs, transactivator of transcription (TAT), and penetratin can be inferred to be the best among all the identified penetration enhancers for drug delivery to the fundus oculi via topical eye drop instillation. Further high-quality experimental studies are required to ascertain their quantitative efficacy. [ABSTRACT FROM AUTHOR]

We report the underlying genetic causes of prelingual hearing loss (HL) segregating in eight large consanguineous families, ascertained from the Punjab province of Pakistan. Exome sequencing followed by segregation analysis revealed seven potentially pathogenic variants, including four novel alleles c.257G>A, c.6083A>C, c.89A>G, and c.1249A>G of CLPP, CDH23, COL4A5, and LARS2, respectively. We also identified three previously reported HL-causing variants (c.4528C>T, c.35delG, and c.1219T>C) of MYO15A, GJB2, and TMPRSS3 segregating in four families. All identified variants were either absent or had very low frequencies in the control databases. Our in silico analyses and 3-dimensional (3D) molecular modeling support the deleterious impact of these variants on the encoded proteins. Variants identified in MYO15A, GJB2, TMPRSS3, and CDH23 were classified as "pathogenic" or "likely pathogenic", while the variants in CLPP and LARS2 fall in the category of "uncertain significance" based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant pathogenicity guidelines. This paper highlights the genetic diversity of hearing disorders in the Pakistani population and reports the identification of four novel mutations in four HL families. [ABSTRACT FROM AUTHOR]

• A photo-switch to control PDS non-radical/radical activation over CFO is developed. • Non-radical activation has high PDS utilization and less halogenated byproduct generation. • Radical activation has fast degradation rate and strong mineralization ability for pollutants. • QSARs of phenolic pollutants were found to provide instructions of pathway choice. This work presents a novel strategy for peroxydisulfate (PDS) activation under controlled non-radical/radical mechanism, which is based on a photo-switch over layered CuFe oxide (CFO). The non-radical mechanism is attained by CFO under dark environment, and the radical mechanism is achieved through the visible light irradiation. Electron paramagnetic resonance (EPR) and density functional theory (DFT) studies demonstrate the non-radical activation mechanism is conducted by the polarization effect of CFO to PDS molecule. The radical mechanism could be elucidated by the one-electron reduction of the PDS by excited electrons on conduction band of CFO. Products analyses based on HPLC-MS and Fukui functions suggest that the non-radical degradation pathway could decrease the generation of halide intermediates, whereas the radical pathway may not be observed with this property. Quantitative structure-activity relationships (QSARs) were established between the observed pseudo-first-order rates of various phenolic pollutants and the classical descriptors (i.e., Hammett constant, Pka, E HOMO and E LUMO) in the non-radical and radical systems, respectively, to give instructions of pathway choice for different pollutants. Considering the non-radical/radical pathway both have their own unique strengths (e.g., non-radical pathway has high selectivity to pollutants and high utilization efficiency of oxidant, and radical pathway has considerable degradation rate and strong mineralization ability), these pathways should be chosen wisely for pollutant degradation according to reality conditions. [ABSTRACT FROM AUTHOR]

In this work, corn straw (CS) based porous carbon was prepared by one-step phosphoric acid (H 3 PO 4) low temperature activation. The impregnation ratios (H 3 PO 4 /CS, g/g) played an important role in the pore development. ACS 300-1 engineered at 300 °C and the impregnation ratio of 1.0 showed the maximal specific surface area of 463.89 m2/g with total pore volume of 0.387 cm3/g, attaining a high tetracycline (TC) uptake of 227.3 mg/g. The adsorption of TC onto ACS 300-1 was found tolerant with wide pH (2.0–10.0) and high ionic strength (0 – 0.5 M). The adsorption data can be fitted well by the pseudo-second order kinetic model and Langmuir isotherm model. The endothermic and spontaneous properties of the adsorption system was implied by Thermodynamic study. The findings of the current work conclude that one-step H 3 PO 4 activation is a green and promising method for corn straw based porous carbon that may be found with great potentials in antibiotic containing wastewater treatment. Image 1 • Corn straw based porous carbon (ACS 300-1) was facilely prepared by one-step phosphoric acid low temperature activation. • ACS 300-1 showed high microporosity and specific surface area with excellent TC uptake capacity of 227.3 mg/g. • ACS 300-1 was tolerant with wide pH (2.0–10.0) and high ionic strength (0–0.5 M). • The adsorption behavior of TC onto ACS 300-1 surface was both physisorption and chemisorption. [ABSTRACT FROM AUTHOR]

Hearing loss is a genetically heterogeneous disorder affecting approximately 360 million people worldwide and is among the most common sensorineural disorders. Here, we report a genetic analysis of seven large consanguineous families segregating prelingual sensorineural hearing loss. Whole-exome sequencing (WES) revealed seven different pathogenic variants segregating with hearing loss in these families, three novel variants (c.1204G>A, c.322G>T, and c.5587C>T) in TMPRSS3, ESRRB, and OTOF, and four previously reported variants (c.208C>T, c.6371G>A, c.226G>A, and c.494C>T) in LRTOMT, MYO15A, KCNE1, and LHFPL5, respectively. All identified variants had very low frequencies in the control databases and were predicted to have pathogenic effects on the encoded proteins. In addition to being familial, we also found intersibship locus heterogeneity in the evaluated families. The known pathogenic c.226C>T variant identified in KCNE1 only segregates with the hearing loss phenotype in a subset of affected members of the family GCNF21. This study further highlights the challenges of identifying disease-causing variants for highly heterogeneous disorders and reports the identification of three novel and four previously reported variants in seven known deafness genes. [ABSTRACT FROM AUTHOR]

This research work was carried out to determine the effects of water contamination on the fatty acid (FA) profile of periphyton, zoobenthos, two Chinese carps and a common carp (Hypophthalmichthys molitrix, Ctenopharygodon idella and Cyprinus carpio), captured from highly polluted (HP), less polluted (LP), and non-polluted (NP) sites of the Indus river. We found that the concentration of heavy metals in the river water from the polluted locations exceeded the permissible limits suggested by the World Health Organization (WHO) and the US Environmental Protection Agency (EPA). Fatty acid profiles in periphyton, zoobenthos, H. molitrix, C. idella, and C. carpio in the food web of river ecosystems with different pollution levels were assessed. Lauric acid and arachidic acids were not detected in the biomass of periphyton and zoobenthos from HP and LP sites compared to NP sites. Alpha-linolenic acid (ALA), eicosadienoic acid and docosapentaenoic acid were not recorded in the biomass samples of periphyton and zoobenthos in both HP and LP sites. Caprylic acid, lauric acid, and arachidic acid were not found in H. molitrix, C. idella, and C. carpio captured from HP. In this study, 6 and 9 omega series FAs were identified in the muscle samples of H. molitrix, C. idella and C. carpio captured from HP and LP sites compared to NP sites, respectively. Less polyunsaturated fatty acids were observed in the muscle samples of H. molitrix, C. idella, and C. carpio collected from HP than from LP. The heavy metals showed significant negative correlations with the total FAs in periphyton, zoobenthos, and fish samples. [ABSTRACT FROM AUTHOR]

Juvenile open angle glaucoma (JOAG), which is an uncommon form of primary open angle glaucoma, is a clinically and genetically heterogeneous disorder. We report on a family with a recessively inherited form of JOAG. The proband has a superior and an inferior never fiber layer thinning in both the eyes and the nasal visual field (VF) defects in the left eye, which are clinical findings consistent with glaucomatous optic neuropathy. Whole exome sequencing revealed two novel compound heterozygous variants [c.2966C>G, p.(Pro989Arg); c.5235T>G, p.(Asn1745Lys)] in latent transforming growth factor-beta-binding protein 2 (LTBP2) segregating with the phenotype. Both these variants are predicted to replace evolutionary conserved amino acids, have a pathogenic effect on the encode protein, and have very low frequencies in the control databases. Mutations in LTBP2 are known to cause the Weill-Marchesani syndrome and a Weill-Marchesani-like syndrome, which include glaucoma in their clinical presentation. However, to our knowledge, this is the first published case of a JOAG subject associated with recessively inherited variants of LTPB2 and, thus, expands the repertoire of the known genetic causes of JOAG and the phenotypic spectrum of LTBP2 alleles. [ABSTRACT FROM AUTHOR]

After injury to the spinal cord, edema contributes to the underlying detrimental pathophysiological outcomes that lead to worsening of function. Several related membrane proteins called aquaporins (AQPs) regulate water movement in fluid transporting tissues including the spinal cord. Within the cord, AQP1, 4 and 9 contribute to spinal cord injury (SCI)-induced edema. AQP1, 4 and 9 are expressed in a variety of cells including astrocytes, neurons, ependymal cells, and endothelial cells. This review discusses some of the recent findings of the involvement of AQP in SCI and highlights the need for further study of these proteins to develop effective therapies to counteract the negative effects of SCI-induced edema. [ABSTRACT FROM AUTHOR]

Nonsyndromic oculocutaneous Albinism (nsOCA) is clinically characterized by the loss of pigmentation in the skin, hair, and iris. OCA is amongst the most common causes of vision impairment in children. To date, pathogenic variants in six genes have been identified in individuals with nsOCA. Here, we determined the identities, frequencies, and clinical consequences of OCA alleles in 94 previously unreported Pakistani families. Combination of Sanger and Exome sequencing revealed 38 alleles, including 22 novel variants, segregating with nsOCA phenotype in 80 families. Variants of TYR and OCA2 genes were the most common cause of nsOCA, occurring in 43 and 30 families, respectively. Twenty-two novel variants include nine missense, four splice site, two non-sense, one insertion and six gross deletions. In vitro studies revealed retention of OCA proteins harboring novel missense alleles in the endoplasmic reticulum (ER) of transfected cells. Exon-trapping assays with constructs containing splice site alleles revealed errors in splicing. As eight alleles account for approximately 56% (95% CI: 46.52-65.24%) of nsOCA cases, primarily enrolled from Punjab province of Pakistan, hierarchical strategies for variant detection would be feasible and cost-efficient genetic tests for OCA in families with similar origin. Thus, we developed Tetra-primer ARMS assays for rapid, reliable, reproducible and economical screening of most of these common alleles. [ABSTRACT FROM AUTHOR]