Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression.

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.-69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.-69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.-69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration.

Whole-genome sequencing of diverse wheat accessions uncovers genetic changes during modern breeding in China and the United States.

Breeding has dramatically changed the plant architecture of wheat (Triticum aestivum), resulting in the development of high-yielding varieties adapted to modern farming systems. However, how wheat breeding shaped the genomic architecture of this crop remains poorly understood. Here, we performed a comprehensive comparative analysis of a whole-genome resequencing panel of 355 common wheat accessions (representing diverse landraces and modern cultivars from China and the United States) at the phenotypic and genomic levels. The genetic diversity of modern wheat cultivars was clearly reduced compared to landraces. Consistent with these genetic changes, most phenotypes of cultivars from China and the United States were significantly altered. Of the 21 agronomic traits investigated, 8 showed convergent changes between the 2 countries. Moreover, of the 207 loci associated with these 21 traits, more than half overlapped with genomic regions that showed evidence of selection. The distribution of selected loci between the Chinese and American cultivars suggests that breeding for increased productivity in these 2 regions was accomplished by pyramiding both shared and region-specific variants. This work provides a framework to understand the genetic architecture of the adaptation of wheat to diverse agricultural production environments, as well as guidelines for optimizing breeding strategies to design better wheat varieties.

Obesity-Facilitated Colon Cancer Progression Is Mediated by Increased Diacylglycerol O-Acyltransferases 1 and 2 Levels.

BACKGROUND & AIMS: The obesity epidemic is associated with increased colon cancer progression. As lipid droplets (LDs) fuel tumor growth, we aimed to determine the significance of diacyltransferases (diacylglycerol o-acyltransferases 1 and 2 [DGAT1/2]), responsible for LD biogenesis, in obesity-mediated colonic tumorigenesis. METHODS: Human colon cancer samples, colon cancer cells, colonospheres, and ApcMin/+ colon cancer mouse model on a high-fat diet were employed. For DGAT1/2 inhibition, enzymatic inhibitors and small interfering RNA were used. Expression, pathways, cell cycle, and growth were assessed. Bioinformatic analyses of CUT&RUN and RNA sequencing data were performed. RESULTS: DGAT1/2 levels in human colon cancer tissue are significantly elevated with disease severity and obesity (vs normal). Their levels are increased in human colon cancer cells (vs nontransformed) and further enhanced by fatty acids prevalent in obesity; augmented DGAT2 expression is MYC-dependent. Inhibition of DGAT1/2 improves FOXO3 activity by attenuating PI3K, resulting in reduced MYC-dependent DGAT2 expression and accumulation of LDs, suggesting feedback. This inhibition attenuated growth in colon cancer cells and colonospheres via FOXO3/p27kip1 cell cycle arrest and reduced colonic tumors in ApcMin/+ mice on a high-fat diet. Transcriptomic analysis revealed that DGAT1/2 inhibition targeted metabolic and tumorigenic pathways in human colon cancer and colon cancer crypts, stratifying human colon cancer samples from normal. Further analysis revealed that this inhibition is predictive of advanced disease-free state and survival in patients with colon cancer. CONCLUSIONS: This is a novel mechanism of DGAT1/2-dependent metabolic and tumorigenic remodeling in obesity-facilitated colon cancer, providing a platform for future development of effective treatments for patients with colon cancer.

Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans.

Human infertility is a multifactorial disease that affects 8%-12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs∗2]) from a consanguineous Pakistani family with two males suffering from non-obstructive azoospermia (NOA) and one female diagnosed with premature ovarian insufficiency (POI) as well as a nonsense mutation (c.958G>T [p.Glu320∗]) and a splicing mutation (c.1180-3C>G) in two unrelated Chinese men (individual P3907 and individual P6032, respectively) with meiotic arrest. Mutations in C14orf39 resulted in truncated proteins that retained SYCE1 binding but exhibited impaired polycomplex formation between C14ORF39 and SYCE1. Further cytological analyses of meiosis in germ cells revealed that the affected familial males with the C14orf39 frameshift mutation displayed complete asynapsis between homologous chromosomes, while the affected Chinese men carrying the nonsense or splicing mutation showed incomplete synapsis. The phenotypes of NOA and POI in affected individuals were well recapitulated by Six6os1 mutant mice carrying an analogous mutation. Collectively, our findings in humans and mice highlight the conserved role of C14ORF39/SIX6OS1 in SC assembly and indicate that the homozygous mutations in C14orf39/SIX6OS1 described here are responsible for infertility of these affected individuals, thus expanding our understanding of the genetic basis of human infertility.

Combined effect of endophytic Bacillus mycoides and rock phosphate on the amelioration of heavy metal stress in wheat plants.

BACKGROUND: Zinc (Zn) and nickel (Ni) are nutrients that are crucial for plant growth; however, when they are present at higher concentrations, they can cause toxicity in plants. The present study aimed to isolate plant growth promoting endophytic bacteria from Viburnum grandiflorum and assess its plant and defense promoting potential alone and in combination with RP in zinc (Zn) and nickel (Ni) toxic soil. The isolated endophytic bacteria were identified using 16s rRNA gene sequencing. For the experiment, twelve different treatments were applied using Zn, Ni, isolated endophytic Bacillus mycoides (Accession # MW979613), and rock phosphate (RP). The Ni, Zn and RP were used at the rate of (100 mg/kg) and (0.2 g/kg) respectively. A pot experiment with three replicates of each treatment was conducted using a complete randomized design (CRD). RESULTS: The results indicated that Ni (T5 = seed + 100 mg/kg Ni and T9 = seed + 100 mg/kg Zn) and Zn concentrations inhibited plant growth, but the intensity of growth inhibition was higher in Ni-contaminated soil. Bacillus mycoides and RP at 100 mg/Kg Zn (T12 = inoculated seed + 100 mg/kg Zn + RP0.2 g/kg.) increased the shoot length, leaf width, protein and sugar content by 57%, 13%, 20% and 34%, respectively, compared to the control. The antioxidant enzymes superoxide dismutases (SOD), peroxidase (POD) were decreased in contaminated soil. Furthermore, Ni and Zn accumulation was inhibited in T11 (seed + 100 mg/kg Zn + RP0.2 g/Kg) and T12 (inoculated seed + 100 mg/kg Zn + RP0.2 g/Kg) by 62 and 63% respectively. The Cu, Ca, and K, contents increased by 128, 219 and 85, Mn, Na, and K by 326, 449, and 84% in (T3 = inoculated seed) and (T4 = inoculated seed + RP 0.2 g/Kg) respectively. CONCLUSIONS: Ni was more toxic to plants than Zn, but endophytic bacteria isolated from Viburnum grandiflorum, helped wheat (Triticum aestivum) plants and reduced the toxic effects of Ni and Zn. The effect of Bacillus mycoides was more prominent in combination with RP which promoted and suppressed heavy-metal toxicity. The reported combination of Bacillus mycoides and RP may be useful for improving plant growth and overcoming metal stress.

TALE gene family: identification, evolutionary and expression analysis under various exogenous hormones and waterlogging stress in Cucumis sativus L.

BACKGROUND: Three Amino acid Loop Extension (TALE) belongs to the homeobox group of genes that are important constituents of plant systems. The TALE gene family is instrumental not only in growth and development but also plays an essential role in regulating plant response to environmental adversaries. RESULTS: In the present study, we isolated 21 CsTALE genes from the cucumber (Cucumis sativus L.) genome database. Bioinformatics tools were put in place to understand the structural and functional components of the CsTALE gene family. The evolutionary analysis dissected them into seven subclades (KNOX-I, KNOX-II, and BELL-I to BELL-V). The cis-acting elements in the promoter region of CsTALE genes disclosed that they are key regulators of hormonal and stress-related processes. Additionally, the STRING database advocated the concerting role of CsTALE proteins with other key transcription factors potent in plant developmental biology. The CsmiR319 and CsmiR167a-3p targeting the CsTALE15 and CsTALE16, respectively, further assert the importance of the CsTALE gene family posttranscriptional-related processes. Tissue-specific gene expression unfolded the fundamental involvement of CsTALE genes as they were expressed throughout the developmental stages. Under waterlogging stress, the CsTALE17 expressed significantly higher values in WL, WL-NAA, and WL-ETH but not in WL-MeJA-treated samples. CONCLUSIONS: The present study reveals the evolution and functions of the CsTALE gene family in cucumber. Our work will provide a platform that will help future researchers address the issue of waterlogging stress in the Yangtze River Delta.

Identifying the hidden parasitic intruders: Molecular insights into the health of common Myna.

Birds are known to act as the parasite reservoir and can transmit them to other organisms through food chains. This study aims to report the molecular prevalence and phylogenetic evaluation of various blood borne pathogens (Toxoplasma gondii, Isospora spp., Plasmodium spp., Haemoproteus spp., Leucocytozoan spp. and Neospora caninum) in blood samples of common Myna (Acridotheres tristis: N = 80) collected from four region (Jhang, Khanewal, Multan and Muzaffargarh) in Punjab Pakistan. Effect of pathogens on the complete blood count of the host was also determined. Results revealed by 2/80 Myna (2.5 %) amplified ITS-1 gene of Toxoplasma (T.) gondii (confirmed by DNA sequencing) while 2/80 (2.5 %) birds amplified 18S rDNA gene and Isospora spp. Phylogenetic analysis of both pathogens showed that Pakistani isolates were clustered together and were closely related to isolates that were reported from worldwide countries. Risk factor analysis revealed that prevalence of both pathogens was not restricted to a particular sampling site or a particular bird sex (P > 0.05). T. gondii infected birds had elevated red cell distribution width while Isospora sp. infected birds had elevated % monocytes and platelet distribution width while decreased mean cell hemoglobin, mean corpuscular hemoglobin concentration and platelets hematocrit than their respective uninfected birds. In conclusion, we are reporting the presence of T. gondii and Isospora sp. among Pakistani common Myna that had disturbed the complete blood count parameters that may have affected their normal physiology.

Antiferromagnetism and Phase Stability of CrMnFeCoNi High-Entropy Alloy.

It has long been suspected that magnetism could play a vital role in the phase stability of multicomponent high-entropy alloys. However, the nature of the magnetic order, if any, has remained elusive. Here, by using elastic and inelastic neutron scattering, we demonstrate evidence of antiferromagnetic order below ∼80 K and strong spin fluctuations persisting to room temperature in a single-phase face-centered cubic (fcc) CrMnFeCoNi high-entropy alloy. Despite the chemical complexity, the magnetic structure in CrMnFeCoNi can be described as γ-Mn-like, with the magnetic moments confined in alternating (001) planes and pointing toward the ⟨111⟩ direction. Combined with first-principles calculation results, it is shown that the antiferromagnetic order and spin fluctuations help stabilized the fcc phase in CrMnFeCoNi high-entropy alloy.

Leading report of molecular prevalence of tick borne Anaplasma marginale and Theileria ovis in yaks (Bos grunniens) from Pakistan.

Domestic yak (Bos grunniens) is an economically important feature of the mountainous region of Gilgit-Baltistan in Pakistan where agriculture is restricted and yaks play multiple roles which includes being a source of milk, meat, hides, fuel and power. However little is known about the parasitic infections in Pakistani yaks. Aim of this research was to report the prevalence and genetic diversity of protozoa parasite (Theileria ovis, 18 S rDNA gene was targeted) and an obligate bacterium (Anaplasma marginale, msp-1 gene was amplified) in the blood that was sampled from 202 yaks collected from four districts in Gilgit-Baltistan during January 2023 till January 2024. Results revealed that 6/202 (3%) yaks were of Theileria ovis while 8/202 (4%) were Anaplasma marginale infected. Positive PCR products of both parasites were confirmed by DNA sequencing and their similarity with previously available pathogen sequences was determined by BLAST analysis. Phylogenetic tree indicated that isolates of both parasites displayed genetic. Anaplasma marginale infection varied with the sampling districts and Shigar district had the highest rate of bacterial infection. Cows were significantly more prone to Theileria ovis infection than bulls. Calf and hybrid yaks were more prone to Anaplasma marginale infection. In conclusion, this is the first report that yaks residing the Gilgit-Baltistan region in Pakistan are infected with Theileria ovis and Anaplasma marginale. Similar larger scales studies are recommended in various regions of Gilgit-Baltistan to document the infection rates of these parasites to formulate strategies that will lead to the effective control of these pathogens.

Trends in extracting protein from microalgae Spirulina platensis, using innovative extraction techniques: mechanisms, potentials, and limitations.

Microalgal, species are recognized for their high protein content, positioning them as a promising source of this macronutrient. Spirulina platensis, in particular, is noteworthy for its rich protein levels (70 g/100 g dw), which are higher than those of meat and legumes. Incorporating this microalgae into food can provide various benefits to human health due to its diverse chemical composition, encompassing high amount of protein and elevated levels of minerals, phenolics, essential fatty acids, and pigments. Conventional techniques employed for protein extraction from S. platensis have several drawbacks, prompting the exploration of innovative extraction techniques (IETs) to overcome these limitations. Recent advancements in extraction methods include ultrasound-assisted extraction, microwave-assisted extraction, high-pressure-assisted extraction, supercritical fluid extraction, pulse-electric field assisted extraction, ionic liquids assisted extraction, and pressurized liquid extraction. These IETs have demonstrated efficiency in enhancing protein yield of high quality while maximizing biomass utilization. This comprehensive review delves into the mechanisms, applications, and drawbacks associated with implementing IETs in protein extraction from S. platensis. Notably, these innovative methods offer advantages such as increased extractability, minimized protein denaturation, reduced solvent consumption, and lower energy consumption. However, safety considerations and the synergistic effects of combined extraction methods warrant further exploration and investigation of their underlying mechanisms.

Improving the enzymatic activity and stability of N-carbamoyl hydrolase using deep learning approach.

BACKGROUND: Optically active D-amino acids are widely used as intermediates in the synthesis of antibiotics, insecticides, and peptide hormones. Currently, the two-enzyme cascade reaction is the most efficient way to produce D-amino acids using enzymes DHdt and DCase, but DCase is susceptible to heat inactivation. Here, to enhance the enzymatic activity and thermal stability of DCase, a rational design software "Feitian" was developed based on kcat prediction using the deep learning approach. RESULTS: According to empirical design and prediction of "Feitian" software, six single-point mutants with high kcat value were selected and successfully constructed by site-directed mutagenesis. Out of six, three mutants (Q4C, T212S, and A302C) showed higher enzymatic activity than the wild-type. Furthermore, the combined triple-point mutant DCase-M3 (Q4C/T212S/A302C) exhibited a 4.25-fold increase in activity (29.77 ± 4.52 U) and a 2.25-fold increase in thermal stability as compared to the wild-type, respectively. Through the whole-cell reaction, the high titer of D-HPG (2.57 ± 0.43 mM) was produced by the mutant Q4C/T212S/A302C, which was about 2.04-fold of the wild-type. Molecular dynamics simulation results showed that DCase-M3 significantly enhances the rigidity of the catalytic site and thus increases the activity of DCase-M3. CONCLUSIONS: In this study, an efficient rational design software "Feitian" was successfully developed with a prediction accuracy of about 50% in enzymatic activity. A triple-point mutant DCase-M3 (Q4C/T212S/A302C) with enhanced enzymatic activity and thermostability was successfully obtained, which could be applied to the development of a fully enzymatic process for the industrial production of D-HPG.

Nutrition and Dietary Intervention in Cancer: Gaps, Challenges, and Future Perspectives.

The term "cancer" refers to the state in which cells in the body develop mutations and lose control over their replication. Malignant cancerous cells invade in various other tissue sites of the body. Chemotherapy, radiation, and surgery are the first-line modalities for the majority of solid cancers. These treatments work by mitigating the DNA damage of cancerous cells, but they can also cause harm to healthy cells. These side effects might be immediate or delayed, and they can cause a high rate of morbidity and mortality. Dietary interventions have a profound impact on whole-body metabolism, including immunometabolism and oncometabolism which have been shown to reduce cancer growth, progression, and metastasis in many different solid tumor models with promising outcomes in early phase clinical studies. Dietary interventions can improve oncologic or quality-of-life outcomes for patients that are undergoing chemotherapy or radiotherapy. In this chapter, we will focus on the impact of nutritional deficiencies, several dietary interventions and their proposed mechanisms which are used as a novel therapy in controlling and managing cancers.

Genetic Signature Controlling Root System Architecture in Diverse Spring Wheat Germplasm.

Roots are the main sensing organ, initiating multiple signaling pathways in response to abiotic factors, including nutrients, drought, and salt stress. A focus on improving the root system architecture is a key strategy to mitigate these stresses in wheat crop. In the present study, a diversity panel comprising indigenous landraces and historical cultivars from Pakistan was characterized for the root system architecture (RSA) and important loci were identified using a genome-wide association study (GWAS). RSA of the diversity panel was characterized 30 days after sowing in brunch tubes, and root images were taken. A high-throughput root imaging analysis using Rhizovision software was performed by setting the scale to extract the eight RSA traits and four plant biomass-related traits. GWAS identified 323 association signals for 12 root and biomass traits present on all wheat chromosomes, while the most important and reliable genetic loci (based on pleotropic loci and candidate genes) were identified on chromosomes 2A, 2B, 5A, 5D, 6A, 7B, and 7D for RSA. SNP annotation and transcriptome profiling identified nine candidate genes regulating the RSA and plant biomass traits, including ROOTLESS WITH UNDETECTABLE MERISTEM1, MYB TRANSCRIPTION FACTOR4, BRASSINOSTEROID INSENSITIVE1, SLENDER RICE1, AUXIN-RESPONSIVE FACTOR25, SCARECROW, NARROW LEAF2, PIN-FORMED1 AND PHOSPHATE TRANSCRIPTION FACTOR1. This study provided pre-breeding information for deep-rooting genotypes and associated markers that will accelerate the incorporation of such traits in breeding.

Hemodynamic Renal Reserve Response in Conscious Normotensive and Hypertensive Mice.

INTRODUCTION: Renal function may be compromised following recovery from kidney insults. Renal functional reserve (RFR) is a measure of the difference between the kidney's maximum capacity and its baseline function, which helps identify any areas of the kidney with compromised function. Usually, RFR is evaluated using acute volume expansion (AVE), but this is typically done in anesthetized animals, which may not accurately represent the kidney's complete functional capacity. In this study, we have introduced a novel method that enables AVE to be conducted in conscious mice. METHODS: We have implemented this innovative approach in two animal models representing either intact or impaired renal function, specifically utilizing a lower nephron hypertensive model. Mice were implanted with radio-transmitters for mean artery blood pressure (MAP) monitoring during the experiment. After recovery, half of the mice were induced hypertension by right kidney nephrectomy combined with the ligation of the upper branch of the left kidney. For the AVE, a volume equivalent to 5% of the mouse's body weight was administered via intravenous (IV) or intraperitoneal bolus injection. Subsequently, the mice were individually housed in cages covered with plastic wrap. Urine was collected every hour for a total of 3 h for the measurement of urine and sodium excretion. RESULTS: The MAPs for all normotensive mice were consistent throughout the AVE, but it increased 5-16 mm Hg in the hypertensive mice upon AVE. Remarkably, conscious mice exhibited a significantly stronger response to IV-administered AVE when compared to anesthetized mice. This response was evident in the increase in urinary flow, which was approximately 170% and 145% higher in conscious normotensive and hypertensive mice, respectively, compared to their respective baselines. In contrast, anesthetized normotensive and hypertensive mice showed only around a 130% and 100% increase in urinary flow, respectively. Additionally, upon AVE, conscious normotensive mice excreted approximately 47% more sodium than conscious hypertensive mice. In contrast, anesthetized normotensive mice excreted only about 30% more sodium than their anesthetized hypertensive counterparts. CONCLUSION: Performing a kidney stress test with a significant solution load in conscious mice seems to be a superior method for evaluating RFR compared to conducting the test under anesthesia. Assessing kidney clearance while the mice are conscious has the potential to enhance the precision of diagnosing and predicting both acute and chronic kidney diseases.

Contaminant transport from solid waste dumps: Implications for environmental degradation with a focus on capital territory regions.

Open dumping of Municipal solid waste is the main method of solid waste management in Pakistan. To investigate the impacts of leachate transportation from these waste dumps on groundwater quality, two sites were selected (I-12 in Islamabad and Lohsar in Rawalpindi), water samples were collected from existing wells during summer, winter, and rainy seasons and were analyzed for physiochemical parameters using standard methods. Most groundwater samples showed contamination and values of various parameters exceeded the desired limits set by the World Health Organization (WHO) and the National Standard for Drinking Water Quality (NSDWQ), especially during the rainy season, whereas the least contamination in groundwater samples was observed during the winter season. The results obtained were, pH: 5.75-7.87, Electrical Conductivity (EC): 103-3460 µS cm-1, Total Dissolved Solids (TDS): 436-4425 mg L-1, Total Alkalinity (TA): 190-1330 mg L-1, Total Hardness (TH): 128-676 mg L-1, Chlorides (Cl⁻): 56.7-893.3 mg L-1, Nitrates (NO3⁻): 7.8-19.9 mg L-1, Dissolved Oxygen (DO): 6.1-20.8 mg L-1, Biological Oxygen Demand (BOD): 1.0-44.0 mg L-1 and Chemical Oxygen Demand (COD): 56-272 mg L-1. The findings suggest that the magnitude of groundwater contamination from leachate transportation is intricately influenced by factors such as leachate composition, seasonal variations and distance from the dumpsite. The contamination level reduced along the distance from the dumps. Except Copper (Cu) and Zinc (Zn), the concentration of all other heavy metals including, Iron (Fe), Chromium (Cr), Nickel (Ni), Lead (Pb), Cadmium (Cd) was found above standard appreciable limits. The t-test showed a significant difference in parameter concentrations for all seasons except for Cd and Zn. The calculation of water quality index through CCME (Canadian Council of Ministers of Environment) model revealed that all the groundwater samples around both the dump sites were of poor and marginal quality. In general, the groundwater quality of both study areas is not suitable for the drinking purpose. The study suggests regular testing and treating groundwater before use, use of engineered landfills, covering landfills with clay and vegetation and use of alternative strategies like composting and recycling for waste management.

Wood biochar induced metal tolerance in Maize (Zea mays L.) plants under heavy metal stress.

Due to metal toxicity, widespread industrialization has negatively impacted crop yield and soil quality. The current study was aimed to prepare and characterize biochar made from wood shavings of Pinus roxburghii and to determine the plant growth promoting and heavy metal detoxification of cadmium (Cd) and chromium (Cr) contaminated soil. FTIR SEM coupled with EDX characterization of biochar was performed; Cd and Cr were used at a rate of 20 mg/kg. Biochar was used at the rate of 50 mg/kg for various treatments. The completely randomized design (CRD) was used for the experiment and three replicates of each treatment were made. Various agronomic and enzymatic parameters were determined. The results indicated that all growth and enzymatic parameters were enhanced by the prepared biochar treatments. The most prominent results were observed in treatment T5 (in which shoot length, root length, peroxidase dismutase (POD), superoxide dismutase (SOD) catalyzes (CAT), and chlorophyll a and b increased by 28%, 23%, 40%, 41%, 42%, and 27%, respectively, compared to the control). This study demonstrated that biochar is a sustainable and cost-effective approach for the remediation of heavy metals, and plays a role in plant growth promotion. Farmers may benefit from the current findings, as prepared biochar is easier to deliver and more affordable than chemical fertilizers. Future research could clarify how to use biochar optimally, applying the minimum amount necessary while maximizing its benefits and increasing yield.

Body composition markers are associated with changes in inflammatory markers but not vice versa: A bi-directional longitudinal analysis in a population-based sample.

BACKGROUND AND AIM: Growing body of evidence consistently link obesity and inflammation, Although the direction of the association is still unclear. We aimed to investigate longitudinal associations of body anthropometric, composition and fat distribution parameters with inflammatory markers and vice versa. METHOD AND RESULTS: We used data from 2464 individuals of the SHIP-TREND cohort with a median follow-up of 7 years. Linear regression models adjusted for confounders were used to analyze associations of standardized body composition markers derived from classic anthropometry, bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) at baseline with changes in inflammatory markers (C-reactive protein (CRP), white blood cell (WBC), fibrinogen) and vice versa. Higher level of anthropometric markers at baseline were associated with an increase in the change of inflammatory markers. A 13.5 cm higher waist circumference (WC), 16.0 kg body weight and 7.76 % relative fat mass (FM) at baseline was associated with a change in CRP of 0.52 mg/L (95 % confidence interval [CI]: 0.29 to 0.74), 0.51 mg/L (95 % CI: 0.29; 0.74) and 0.58 mg/L (95 % CI: 0.34; 0.82) respectively. Absolute FM showed the strongest association with changes in serum fibrinogen levels (ß for 8.69 kg higher FM: 0.07 g/L; 95 % CI: 0.05; 0.09). Baseline inflammatory markers were only associated with changes in hip circumference. CONCLUSION: Our study indicates the importance of anthropometric, body composition and fat distribution markers as a risk factor for the development of inflammation. To prevent inflammatory-related complications, important is to take measures against the development of obesity.

Dual AAV-based PCDH15 gene therapy achieves sustained rescue of visual function in a mouse model of Usher syndrome 1F.

Mutations in the PCDH15 gene, encoding protocadherin-15, are among the leading causes of Usher syndrome type 1 (USH1F), and account for up to 12% USH1 cases worldwide. A founder truncating variant of PCDH15 has a ∼2% carrier frequency in Ashkenazi Jews accounting for nearly 60% of their USH1 cases. Although cochlear implants can restore hearing perception in USH1 patients, presently there are no effective treatments for the vision loss due to retinitis pigmentosa. We established a founder allele-specific Pcdh15 knockin mouse model as a platform to ascertain therapeutic strategies. Using a dual-vector approach to circumvent the size limitation of adeno-associated virus, we observed robust expression of exogenous PCDH15 in the retinae of Pcdh15KI mice, sustained recovery of electroretinogram amplitudes and key retinoid oxime, substantially improved light-dependent translocation of phototransduction proteins, and enhanced levels of retinal pigment epithelium-derived enzymes. Thus, our data raise hope and pave the way for future gene therapy trials in USH1F subjects.

Photodynamic therapy in management of cutaneous leishmaniasis: A systematic review.

This systematic review evaluated the efficacy and safety of photodynamic therapy (PDT) in the management of cutaneous leishmaniasis (CL). The electronic search for identification of relevant studies, adhered to the PICOS (Population, Intervention, Comparator, Outcomes and Study type) framework, was conducted through PubMed, Google scholar, Dimensions, X-mol, and Semantic Scholar till December 2023. All types of studies reporting PDT in the management of CL with no language restriction were included. Methodological quality appraised of the selected studies was performed using Jadad index. Of the 317 identified studies, 21 reported PDT for the treatment of CL lesions, consisting of two randomized controlled trials (RCTs), four single-center open study, one case series and 14 case reports. Collectively, these studies presented a total of 304 patients with ages ranging from 1 to 82 years, undergoing varying number of PDT sessions (3-28) and follow-up durations spanning 4 weeks to 24 months. The CL lesions predominantly manifested on the exposed body areas, such as face, limbs, neck, ear and nose, and characterized with the use of clinical variables, such as plaques, papules, erythema and ulceration. PDT protocols differed in the photosensitizer type, incubation time, light source characteristics (e.g., wavelength, output power, and energy density), duration of light illumination, number of PDT sessions and their respective frequencies. Treatment response was assessed through the clinical presentation (i.e., at the baseline and after PDT completion) or by the absence of Leishmania parasites. Adverse effects comprised of pain, burning and tingling sensation experienced during PDT, followed by erythema, pigmentation changes and edema post-treatment. This systematic review revealed that PDT is an efficacious and safe modality for the treatment of CL, with mild and transient side effects.

Magnetic nanocomposite of maize offal biomass for effective sequestration of Congo red and methyl orange dyes from contaminated water: modeling, kinetics and reusability.

The current study aims to use a facile and novel method to remove Congo red (CR) and Methyl Orange (MO) dyes from contaminated water with Maize offal biomass (MOB) and its nanocomposite with magnetic nanoparticles (MOB/MNPs). The MOB and MOB/MNPs were characterized with Fourier-transform infrared (FTIR), scanning electron microscopy (SEM), BET, XRD and point of zero charge (pHPZC). The influence of initial CR and MO levels (20-320 mg/L), adsorbent dosage (1-3 g/L), pH (3-9), co-exiting ions, temperature (25-45 °C) and time (15-180 min) was estimated. The findings demonstrated that MOB/MNPs exhibited excellent adsorption of 114.75 and 29.0 mg/g for CR and MO dyes, respectively while MOB exhibited 81.35 and 23.02 mg/g adsorption for CR and MO dyes, respectively at optimum pH-5, and dose 2 g/L. Initially, there was rapid dye removal which slowed down until equilibrium was reached. The interfering/competing ions in contaminated water and elevated temperature favored the dyes sequestration. The MOB/MNPs exhibited tremendous reusability and stability. The dyes adsorption was spontaneous, and exothermic with enhanced randomness. The adsorption effects were well explained with Freundlich model, pseudo second order and Elovich models. It is concluded that MOB/MNPs showed excellent, eco-friendly, and cost-effective potential to decontaminate the water.

Nanocomposite of Maize offal biomass demonstrated higher dyes removal.FTIR, SEM, BET, XRD and pH_PZC provided vital evidence for dyes adsorption.MOB/MNPs displayed excellent stability and reusability for dyes adsorption.Groundwater samples exposed a higher dyes removal.Results were validated with equilibrium and kinetic adsorption models.