mRNA context and translation factors determine decoding in alternative nuclear genetic codes.

The genetic code is a set of instructions that determine how the information in our genetic material is translated into amino acids. In general, it is universal for all organisms, from viruses and bacteria to humans. However, in the last few decades, exceptions to this rule have been identified both in pro- and eukaryotes. In this review, we discuss the 16 described alternative eukaryotic nuclear genetic codes and observe theories of their appearance in evolution. We consider possible molecular mechanisms that allow codon reassignment. Most reassignments in nuclear genetic codes are observed for stop codons. Moreover, in several organisms, stop codons can simultaneously encode amino acids and serve as termination signals. In this case, the meaning of the codon is determined by the additional factors besides the triplets. A comprehensive review of various non-standard coding events in the nuclear genomes provides a new insight into the translation mechanism in eukaryotes.

The impact of mRNA poly(A) tail length on eukaryotic translation stages.

The poly(A) tail plays an important role in maintaining mRNA stability and influences translation efficiency via binding with PABP. However, the impact of poly(A) tail length on mRNA translation remains incompletely understood. This study explores the effects of poly(A) tail length on human translation. We determined the translation rates in cell lysates using mRNAs with different poly(A) tails. Cap-dependent translation was stimulated by the poly(A) tail, however, it was largely independent of poly(A) tail length, with an exception observed in the case of the 75 nt poly(A) tail. Conversely, cap-independent translation displayed a positive correlation with poly(A) tail length. Examination of translation stages uncovered the dependence of initiation and termination on the presence of the poly(A) tail, but the efficiency of initiation remained unaffected by poly(A) tail extension. Further study unveiled that increased binding of eRFs to the ribosome with the poly(A) tail extension induced more efficient hydrolysis of peptidyl-tRNA. Building upon these findings, we propose a crucial role for the 75 nt poly(A) tail in orchestrating the formation of a double closed-loop mRNA structure within human cells which couples the initiation and termination phases of translation.

BILATERAL EYE PATCHING MAY IMPROVE CLINICAL OUTCOMES FOR ACUTE PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: Evaluate preoperative bilateral eye patching (BEP) on subretinal fluid and vision in acute primary rhegmatogenous retinal detachments (RRDs). METHODS: Retrospective nonrandomized interventional study of 335 patients with RRD undergoing BEP until surgery (BEP cohort) and separated by the percentage of full-time compliance: high (≥90%), medium (>90% but ≥50%), and low (<50%). Those declining BEP were included (control). All underwent surgery and were followed for ≥3 months. Imaging was obtained immediately before surgery. Best-corrected visual acuity was measured at the longest follow-up and immediately before surgery. SRF and foveal status immediately before surgery were analyzed. RESULTS: Two hundred and forty and 95 patients were in BEP and control cohorts, respectively. Thirty patients presented immediately before surgery for analysis. High (64%) and medium (35%) compliance showed significantly greater ( P < 0.01) SRF reduction compared with low (4%) and control (3%). Mac-off RRD showed significantly greater ( P < 0.01) foveal reattachment with high (29%) and medium (8%) compliance compared with low (2%) and control (1%). Mac-on RRD demonstrated no significant differences ( P ≥ 0.51) in final best-corrected visual acuity among high (0 logarithm of the minimum angle of resolution [logMAR] [median], 20/20 Snellen), medium (0.10 logMAR, 20/25 Snellen), low (0.10 logMAR), and control cohorts (0.10 logMAR). Mac-off RRD demonstrated significantly better final best-corrected visual acuity with high compliance (0.30 logMAR, 20/40 Snellen) compared with low (0.40 logMAR, 20/50 Snellen; P = 0.04) and control (0.60 logMAR, 20/80 Snellen; P = 0.02). CONCLUSION: Preoperative BEP can stabilize or improve subretinal fluid in acute primary RRD. Patients with BEP >50% of the time experienced the greatest benefits.

Immunoglobulin A Nephropathy Presenting in Young Adults as Advanced Chronic Kidney Disease and Posttransplant Early Recurrence: A Case Series.

Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease, leading to chronic kidney disease. The disease is characterized by microscopic hematuria, gross episodic hematuria, hypertension, and subnephrotic proteinuria with or without renal function impairment. It affects individuals of all age groups, commonly seen in 10-40 years of age. It is progressive in nature and leads to chronic kidney disease, necessitating renal replacement therapy. This case series of in a tertiary care hospital in Western India highlights the presentation of this disease in young adults, its aggressive course, its rapid progression, and its early recurrence in the posttransplant period. It also summarizes the treatment recommendations for IgA recurrence in kidney recipients. The disease is known to have a high chance of posttransplant recurrence. Optimizing renin-angiotensin-aldosterone system (RAAS) blockade, blood pressure control, and increasing immunosuppression in rapidly deteriorating cases are the strategies recommended to treat IgA recurrence in kidney transplant recipients.

Levetiracetam ameliorates epileptogenesis by modulating the adenosinergic pathway in a kindling model of epilepsy in mice.

Background: Levetiracetam (LEV) has been found to have an antihyperalgesic effect via acting on the adenosine system. However, the effects of LEV on the modulation of the adenosine system in the brain have not been elucidated in the prevention of seizures and epilepsy. The present study aimed to explore the possible LEV mechanisms of action in the adenosine signaling systems in an animal model of epilepsy. Methodology: A docking study was initially performed to determine the possible interaction of LEV with adenosine A1 receptors (A1Rs) and equilibrative nucleoside transporters-1 (ENT1). The experimental study was divided into an acute seizure test (32 mice distributed into 4 groups) and a chronic kindling model study (40 mice distributed into 5 groups), followed by gene expression analysis and immunohistochemistry. The kindling model lasted 26 days and took 13 subconvulsive doses of pentylenetetrazole (PTZ) to completely kindle the mice in the PTZ control group. Gene expression changes in the A1Rs, potassium inwardly-rectifying channel 3.2 (Kir3.2), and ENT1 in the brain tissue samples of the mice following treatment with LEV were analyzed using reverse transcription-quantitative polymerase chain reaction, and immunohistochemistry was performed for the A1R protein expression. Results: Docking studies predicted a significant interaction of LEV with A1Rs and ENT1 proteins. Results from the acute testing revealed that caffeine (100 mg/kg) and 8-cyclopentyl-1,3-dipropylxanthine (25 mg/kg) significantly reversed the antiseizure effects of LEV by reversing the percent protection and shortening the onset of the first myoclonic jerk (FMJ) and generalized clonic seizures (GCSs). In the PTZ-induced kindling, LEV demonstrated an increased gene expression of A1Rs and Kir3.2 in the brain. LEV also significantly reduced the gene expression of ENT1. Furthermore, the immunohistochemical analysis showed that LEV increased the protein expression of A1Rs in the brain. Conclusion: Based on these results, it can be concluded that LEV modulates epileptogenesis by acting on the adenosine pathway in the central nervous system.

Can electrocoagulation technology be integrated with wastewater treatment systems to improve treatment efficiency?

Considerable amounts of domestic and industrial wastewater that should be treated before reuse are discharged into the environment annually. Electrocoagulation is an electrochemical technology in which electrical current is conducted through electrodes, it is mainly used to remove several types of wastewater pollutants, such as dyes, toxic materials, oil content, chemical oxygen demand, and salinity, individually or in combination with other processes. Electrocoagulation technology used in hybrid systems along with other technologies for wastewater treatment are reviewed in this work, and the articles reviewed herein were published from 2018 to 2021. Electrocoagulation is widely employed in integrated systems with other electrochemical technologies or conventional methods for effective removal of different pollutants with less cost and sometimes over shorter durations of operation. It has also been observed that the hybrid effects besides increasing the removal efficiency can overcome the disadvantages of using electrocoagulation alone, such as less sludge formation, high cost of operation and increased life of the used electrodes, and stable flux of water with longer periods of operation. More than 20 types of other technologies have been combined efficiently with electrocoagulation.

Evaluation of Different Landslide Susceptibility Models for a Local Scale in the Chitral District, Northern Pakistan.

This work evaluates the performance of three machine learning (ML) techniques, namely logistic regression (LGR), linear regression (LR), and support vector machines (SVM), and two multi-criteria decision-making (MCDM) techniques, namely analytical hierarchy process (AHP) and the technique for order of preference by similarity to ideal solution (TOPSIS), for mapping landslide susceptibility in the Chitral district, northern Pakistan. Moreover, we create landslide inventory maps from LANDSAT-8 satellite images through the change vector analysis (CVA) change detection method. The change detection yields more than 500 landslide spots. After some manual post-processing correction, the landslide inventory spots are randomly split into two sets with a 70/30 ratio for training and validating the performance of the ML techniques. Sixteen topographical, hydrological, and geological landslide-related factors of the study area are prepared as GIS layers. They are used to produce landslide susceptibility maps (LSMs) with weighted overlay techniques using different weights of landslide-related factors. The accuracy assessment shows that the ML techniques outperform the MCDM methods, while SVM yields the highest accuracy of 88% for the resulting LSM.

Cheminformatics-Based Discovery of Potential Chemical Probe Inhibitors of Omicron Spike Protein.

During the past two decades, the world has witnessed the emergence of various SARS-CoV-2 variants with distinct mutational profiles influencing the global health, economy, and clinical aspects of the COVID-19 pandemic. These variants or mutants have raised major concerns regarding the protection provided by neutralizing monoclonal antibodies and vaccination, rates of virus transmission, and/or the risk of reinfection. The newly emerged Omicron, a genetically distinct lineage of SARS-CoV-2, continues its spread in the face of rising vaccine-induced immunity while maintaining its replication fitness. Efforts have been made to improve the therapeutic interventions and the FDA has issued Emergency Use Authorization for a few monoclonal antibodies and drug treatments for COVID-19. However, the current situation of rapidly spreading Omicron and its lineages demands the need for effective therapeutic interventions to reduce the COVID-19 pandemic. Several experimental studies have indicated that the FDA-approved monoclonal antibodies are less effective than antiviral drugs against the Omicron variant. Thus, in this study, we aim to identify antiviral compounds against the Spike protein of Omicron, which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor and facilitates virus invasion. Initially, docking-based virtual screening of the in-house database was performed to extract the potential hit compounds against the Spike protein. The obtained hits were optimized by DFT calculations to determine the electronic properties and molecular reactivity of the compounds. Further, MD simulation studies were carried out to evaluate the dynamics of protein-ligand interactions at an atomistic level in a time-dependent manner. Collectively, five compounds (AKS-01, AKS-02, AKS-03, AKS-04, and AKS-05) with diverse scaffolds were identified as potential hits against the Spike protein of Omicron. Our study paves the way for further in vitro and in vivo studies.

Probing CAS database as prospective antiviral agents against SARS-CoV-2 main protease.

The pandemic of COVID-19 has an unprecedented impact on global health and economy. The novel SARS-CoV-2 is recognized as the etiological agent of current outbreak. Because of its contagious human-to-human transmission, it is an utmost global health emergency at present. To mitigate this threat many scientists and researchers are racing to develop antiviral therapy against the virus. Unfortunately, to date no vaccine or antiviral therapeutic is approved thus there is an urgent need to discover antiviral agent to help the individual who are at high risk. Virus main protease or chymotrypsin-like protease plays a pivotal role in virus replication and transcription; thus, it is considered as an attractive drug target to combat the COVID-19. In this study, multistep structure based virtual screening of CAS antiviral database is performed for the identification of potent and effective small molecule inhibitors against chymotrypsin-like protease of SARS-CoV-2. Consensus scoring strategy combine with flexible docking is used to extract potential hits. As a result of extensive virtual screening, 4 hits were shortlisted for MD simulation to study their stability and dynamic behavior. Insight binding modes demonstrated that the selected hits stabilized inside the binding pocket of the target protein and exhibit complementarity with the active site residues. Our study provides compounds for further in vitro and in vivo studies against SARS-CoV-2.

Structure Analysis and Ferroelectric Response of Bi0.5Na0.5TiO3 Nanopowder Synthesized by Sol-Gel Method.

In this work, bismuth sodium titanate, Bi0.5±xNa0.5±yTiO3 (BNT, x, y = -0.05-0.08) nanopowders were produced using the low-temperature sol-gel technique. The effects of deficient and excess amounts of Bi and Na on BNT structure were systemically examined through X-ray powder diffraction (XRD), energy dispersive analysis (EDS) and scanning electron microscope (SEM). The optimized composition of the BNT nanopowder was pelletized and sintered at different temperatures (950°C-1150 °C). Highly dense ceramics possessing pure perovskite phase was observed for the sample sintered at an optimum sintering temperature (1100 °C). The ferroelectric properties were found to increase with an increase in sintering temperature up to 1100 °C and then decrease. This study justifies that Bi and Na non-stoichiometry (proper excess), processing and sintering temperatures play important role in the successful synthesis of BNT ceramics.

Q-switching near-infrared multiwavelength generation by intracavity tungsten-oxide-induced four-wave mixing in an erbium-doped fiber laser.

We report on the generation of a stable multiwavelength Q-switched erbium-doped fiber laser based on tungsten oxide nanoparticles (WO3 NPs) combined with an intracavity comb filter for the first time, to the best of our knowledge. The prepared WO3-PVA thin film has a modulation depth and saturable intensity of 20% and 100 MW/cm2, respectively. A spectrum of up to 15 peaks with a channel spacing of 0.48 nm has been obtained. In the Q-switching regime, a minimum pulse width of 4.24 µs and a maximum repetition rate of 52.49 kHz were achieved at a maximum pump power of 300 mW. The dual effect of WO3 NPs in saturable absorption and high optical nonlinearity has induced pulsed and four-wave mixing effects. Therefore, the intrinsic advantages of WO3 nanomaterial provide a promising source for the realization of a stable multiwavelength fiber laser.

Stable L-band multiwavelength erbium-doped fiber laser based on four-wave mixing using nickel nanofluid.

A simple continuous-wave multiwavelength erbium-doped fiber laser based on four-wave mixing has been successfully demonstrated utilizing nickel nanofluid (Ni-NF) for the first time, to the best of our knowledge. By fine adjustment of the laser diode pump power up to 196 mW and without any intracavity filtering, stable dual-, triple-, and quadruple-lasing lines in the L-band have been observed at 1595.6 nm, 1596.8 nm, 1598 nm, and 1599.2 nm, respectively, with a signal-to-noise ratio ∼43 dB. The induced L-band wavelengths showed high stability with wavelength shifts <0.07 nm and power fluctuation of <3 dB by monitoring the output spectra for a duration of 30 min at room temperature. Taking into account the superiority of Ni-NF in terms of compactness, low cost, and easy fabrication, this design can be practically used in a variety of nonlinear photonic applications.

Dielectrophoresis of Amyloid-Beta Proteins as a Microfluidic Template for Alzheimer's Research.

We employed dielectrophoresis to a yeast cell suspension containing amyloid-beta proteins (Aß) in a microfluidic environment. The Aß was separated from the cells and characterized using the gradual dissolution of Aß as a function of the applied dielectrophoretic parameters. We established the gradual dissolution of Aß under specific dielectrophoretic parameters. Further, Aß in the fibril form at the tip of the electrode dissolved at high frequency. This was perhaps due to the conductivity of the suspending medium changing according to the frequency, which resulted in a higher temperature at the tips of the electrodes, and consequently in the breakdown of the hydrogen bonds. However, those shaped as spheroidal monomers experienced a delay in the Aß fibril transformation process. Yeast cells exposed to relatively low temperatures at the base of the electrode did not experience a positive or negative change in viability. The DEP microfluidic platform incorporating the integrated microtip electrode array was able to selectively manipulate the yeast cells and dissolve the Aß to a controlled extent. We demonstrate suitable dielectrophoretic parameters to induce such manipulation, which is highly relevant for Aß-related colloidal microfluidic research and could be applied to Alzheimer's research in the future.

Spiritual practices and effects of spiritual well-being and depression on elders' self-perceived health.

As the population is quickly ageing, strategies for helping elders to maintain and promote good health and well-being are urgently needed. Self-perceived health is a powerful predictor of mortality, physical morbidity, and disability among elderly people. Delivering culturally competent care is necessary for taking care of elders. Self-perceived health is a powerful predictor of mortality, physical morbidity, and disability among elderly people. Spiritual well-being has been found particularly important for older adults' overall health. This descriptive, correlational and predictive study used data that was collected from a convenience sample (N = 150) to examine the effects of spiritual well-being on the relationship between depression and self-perceived health, and to describe spiritual practices commonly used by Taiwanese elders. Findings from this study revealed that spiritual well-being was positively correlated with self-perceived health, negatively associated with depression, and significantly mediated the relationship between depression and self-perceived health. Relaxation and exercise were the most commonly used spiritual practices by Taiwanese elders. Findings from this study support the important role of spiritual well-being in elders' health and add to the body of knowledge about the spiritual practices used by Taiwanese elders. Nurses and health care providers should deliver culturally appropriate spiritual care to enhance spiritual well-being for elders to maintain good health for diverse elder population.

Genome-Wide Analyses of the NAC Transcription Factor Gene Family in Pepper (Capsicum annuum L.): Chromosome Location, Phylogeny, Structure, Expression Patterns, Cis-Elements in the Promoter, and Interaction Network.

The NAM, ATAF1/2, and CUC2 (NAC) transcription factors form a large plant-specific gene family, which is involved in the regulation of tissue development in response to biotic and abiotic stress. To date, there have been no comprehensive studies investigating chromosomal location, gene structure, gene phylogeny, conserved motifs, or gene expression of NAC in pepper (Capsicum annuum L.). The recent release of the complete genome sequence of pepper allowed us to perform a genome-wide investigation of Capsicum annuum L. NAC (CaNAC) proteins. In the present study, a comprehensive analysis of the CaNAC gene family in pepper was performed, and a total of 104 CaNAC genes were identified. Genome mapping analysis revealed that CaNAC genes were enriched on four chromosomes (chromosomes 1, 2, 3, and 6). In addition, phylogenetic analysis of the NAC domains from pepper, potato, Arabidopsis, and rice showed that CaNAC genes could be clustered into three groups (I, II, and III). Group III, which contained 24 CaNAC genes, was exclusive to the Solanaceae plant family. Gene structure and protein motif analyses showed that these genes were relatively conserved within each subgroup. The number of introns in CaNAC genes varied from 0 to 8, with 83 (78.9%) of CaNAC genes containing two or less introns. Promoter analysis confirmed that CaNAC genes are involved in pepper growth, development, and biotic or abiotic stress responses. Further, the expression of 22 selected CaNAC genes in response to seven different biotic and abiotic stresses [salt, heat shock, drought, Phytophthora capsici, abscisic acid, salicylic acid (SA), and methyl jasmonate (MeJA)] was evaluated by quantitative RT-PCR to determine their stress-related expression patterns. Several putative stress-responsive CaNAC genes, including CaNAC72 and CaNAC27, which are orthologs of the known stress-responsive Arabidopsis gene ANAC055 and potato gene StNAC30, respectively, were highly regulated by treatment with different types of stress. Our results also showed that CaNAC36 plays an important role in the interaction network, interacting with 48 genes. Most of these genes are in the mitogen-activated protein kinase (MAPK) family. Taken together, our results provide a platform for further studies to identify the biological functions of CaNAC genes.

The Mediating Effect of Spiritual Well-being on Depressive Symptoms and Health-related Quality of Life Among Elders.

The purpose of this study was to investigate the mediating effect of spiritual well-being (SWB) on depressive symptoms (DS) and health-related quality of life (HRQOL) among Taiwanese elders. A convenience sample of 150 Taiwanese elders completed self-administrated questionnaires participated in this cross-sectional study. This study revealed that SWB was positively related to HRQOL but negatively correlated with DS. Results of hieratical regression analyses suggested that SWB significantly mediated the relationship between DS and mental components of HRQOL. Findings from this study suggest that nurses and health care providers should develop strategies to enhance spiritual well-being when caring for elders to maintain good health and promote quality of life.

Evaluation of using the Chinese version of the Spirituality Index of Well-Being (SIWB) scale in Taiwanese elders.

PURPOSE: Spirituality and spiritual well-being have emerged as important indicators for one's quality of life and health outcomes. Nursing as a profession is concerned with a holistic approach to improve health and overall well-being. To evaluate the outcomes of holistic nursing interventions, using valid and reliable instruments to assess spiritual well-being becomes necessary. There is a lack of instruments for measuring spiritual well-being in Chinese populations. Little has been known about the feasibility of using the Spirituality Index of Well-Being (SIWB) in Taiwanese elders. The purpose of this cross-sectional study was to evaluate the uses of the translated Chinese version of the Spirituality Index of Well-Being (SIWB-C) with Taiwanese elders. METHODS: A total of 150 individual who were 65 years old or older and living in southern Taiwan were recruited from a public community center. A four-step procedure was used to translate the English version of the SIWB to the traditional Chinese language. Internal consistency, factor analysis, and correlation coefficient were conducted to evaluate the reliability and validity of the SIWB-C. RESULTS: The SIWB-C demonstrated a high internal consistency with Cronbach's alpha .95. The construct validity of SIWB-C was supported by factor analysis and by significant correlations with its subscales and the CES-D scale. CONCLUSION: The psychometric analysis indicates that the SIWB-C is a valid and reliable instrument for measuring spiritual well-being. This instrument provides a feasible and valid approach for assessing Taiwanese elders' spiritual well-being in the future.

Depression and AIDS Preventive Self-efficacy Among Taiwanese Adolescents.

Effectively reducing adolescents' risky sexual behaviors has been an urgent need since the HIV/AIDS infections among young people has been acknowledged as a priority. Self-efficacy has been considered playing an essential role in behavioral changes, and depressed individuals may demonstrate lower self-efficacy. The purpose of this cross-sectional study was to gain insights into self-reported depression among 16-18 years-old Taiwanese adolescents as well as to explore psychosocial predictors of AIDS preventive self-efficacy. A convenience sample of 734 adolescents from southern Taiwan was recruited, and several reliable and valid questionnaires were used to collect data. Descriptive statistics, odds ratio, independent t-test, and hierarchical multiple regression analyses were utilized to analyze data. Results showed that the differences in self-reported depression and in the AIDS preventive self-efficacy varied by gender, substance use, and having sexual experience. Furthermore, depression was a significant predictor of AIDS preventive self-efficacy while controlling the covariates. This study suggests that gender and mental health status such as depression may play significant roles in AIDS preventive self-efficacy. Nurses and health care providers should take the influence of mental health into consideration when designing AIDS preventive interventions for male and female Taiwanese adolescents. The provided information may also enhance psychiatric nurses' capability to provide care and to enhance the prevention of HIV infection for adolescents.

Massive cystic falcine meningioma presented with slight symptoms: a case report.

Introduction and importance: Meningiomas are the most common intracranial tumors while their presence with cysts is relatively low. In general, large ones usually present with severe symptoms and have a high recurrence rate even after total resection which is also difficult. Case presentation: The authors present a case of an elderly patient with a large Falcine meningioma associated with peritumoral cysts. The patient presented with mild symptoms despite the tumor's significant size. Imaging studies revealed a large mass in the falcine region with peritumoral cysts. The patient underwent surgical resection of the tumor, which was completed without complications. Clinical discussion: The atypical presentation of this large Falcine meningioma with peritumoral cysts highlights the variability in clinical manifestations of these tumors. Despite the tumor's size and the presence of peritumoral cysts, the patient experienced mild symptoms and recovered after relatively easy surgery challenging conventional expectations. Conclusion: The successful outcome of this case demonstrates that even large meningiomas can present with mild symptoms. Medical practitioners should not always link the tumor size to the severity of symptoms, recurrence rate, and complexity of surgery.

The effect of having a physician in the triage area on the rate of patients leaving without being seen: A quality improvement initiative at King Fahad Specialist hospital.

OBJECTIVES: To evaluate the effect of the presence of a physician in the triage area on the number of patients who leave without being seen (LWBS) and some of the factors affecting emergency department (ED) crowding. METHODS: This was a pre-post study carried out at King Fahad Specialist Hospital, Dammam, Saudi Arabia. The 3-month study, consisting of 7826 patients, was split into pre-physician and post-physician periods. Variables compared across these periods were the number of LWBS patients, length of hospital stay, time to physician, and time to disposition decision. Statistical analysis was carried out using R version 4.3.0. RESULTS: Our results showed that the presence of a triage physician significantly decreased the number of LWBS patients (p<0.001) and the time taken to encounter an ED physician (p<0.001). However, it did not have any significant impact on the length of hospital stay (p=0.5) or time to disposition decision (p=0.9). CONCLUSION: The appointment of a triage physician has streamlined patient flow and decreased LWBS rates in the ED, demonstrating the need for more thorough research in this area.