Clinical effectiveness and safety of time-lapse imaging systems for embryo incubation and selection in in-vitro fertilisation treatment (TILT): a multicentre, three-parallel-group, double-blind, randomised controlled trial.

BACKGROUND: Time-lapse imaging systems for embryo incubation and selection might improve outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatment due to undisturbed embryo culture conditions, improved embryo selection, or both. However, the benefit remains uncertain. We aimed to evaluate the effectiveness of time-lapse imaging systems providing undisturbed culture and embryo selection, and time-lapse imaging systems providing only undisturbed culture, and compared each with standard care without time-lapse imaging. METHODS: We conducted a multicentre, three-parallel-group, double-blind, randomised controlled trial in participants undergoing IVF or ICSI at seven IVF centres in the UK and Hong Kong. Embryologists randomly assigned participants using a web-based system, stratified by clinic in a 1:1:1 ratio to the time-lapse imaging system for undisturbed culture and embryo selection (time-lapse imaging group), time-lapse imaging system for undisturbed culture alone (undisturbed culture group), and standard care without time-lapse imaging (control group). Women were required to be aged 18-42 years and men (ie, their partners) 18 years or older. Couples had to be receiving their first, second, or third IVF or ICSI treatment and could not participate if using donor gametes. Participants and trial staff were masked to group assignment, embryologists were not. The primary outcome was live birth. We performed analyses using the intention-to-treat principle and reported the main analysis in participants with primary outcome data available (full analysis set). The trial is registered on the International Trials Registry (ISRCTN17792989) and is now closed. FINDINGS: 1575 participants were randomly assigned to treatment groups (525 participants per group) between June 21, 2018, and Sept 30, 2022. The live birth rates were 33·7% (175/520) in the time-lapse imaging group, 36·6% (189/516) in the undisturbed culture group, and 33·0% (172/522) in the standard care group. The adjusted odds ratio was 1·04 (97·5% CI 0·73 to 1·47) for time-lapse imaging arm versus control and 1·20 (0·85 to 1·70) for undisturbed culture versus control. The risk reduction for the absolute difference was 0·7 percentage points (97·5% CI -5·85 to 7·25) between the time-lapse imaging and standard care groups and 3·6 percentage points (-3·02 to 10·22) between the undisturbed culture and standard care groups. 79 serious adverse events unrelated to the trial were reported (n=28 in time-lapse imaging, n=27 in undisturbed culture, and n=24 in standard care). INTERPRETATION: In women undergoing IVF or ICSI treatment, the use of time-lapse imaging systems for embryo culture and selection does not significantly increase the odds of live birth compared with standard care without time-lapse imaging. FUNDING: Barts Charity, Pharmasure Pharmaceuticals, Hong Kong OG Trust Fund, Hong Kong Health and Medical Research Fund, Hong Kong Matching Fund.

Cornichon protein CNIH4 is not essential for mice gametogenesis and fertility.

BACKGROUND: Cornichon is a functionally conserved transmembrane protein family that generally acts as a cargo-sorting receptor and cycles between the ER and the Golgi. Four Cornichon family members (CNIH1-4) have been identified. The key residues responsible for CNIH1-3 to bind to AMPA receptors are not conserved in CNIH4. Additionally, the function of CNIH1-3 in GPCR signaling is less established, while more established in case of CNIH4 protein that interact with GPCR and control their exportation. Many GPCRs are known for their essential roles in male and female gonad development. But whether CNIH4 plays a role in gametogenesis remains unknown. DESIGN: Mice carrying the Cnih4 knockout allele (Cnih4tm1a-/-) were generated by insertion of a LacZ reporter and a polyadenylation site after exon 1. Western blot, Immunofluorescence, computer-aided sperm analysis and other methods were used in the functional analysis. RESULTS: We identified that both Cnih4tm1a-/- male and female mice have normal fertility. Though, the sperm count, morphology, and motility of Cnih4tm1a-/- mice were slightly impaired compared to those of wild-type mice, the testes to body weight ratio and testicular histology were similar to those in control mice. Histological examination of Cnih4tm1a-/- ovaries detected follicles from primordial to antral stages and the numbers of follicles at each stage were also comparable to wild-type controls. Normal fertility was noticed after six-month fertility tests. That was likely due to the compensatory role of Chin3, which significantly upregulated in the Cnih4tm1a-/- mice to preserve the fertility role. CONCLUSION: Despite CNIH4 showing enriched expression in mouse germ cells, our genetic knockout studies demonstrated that CNIH4 is not essential for gametogenesis and fertility in mice although with a slight reduction in count, motility and morphology of sperm in male mice.

A novel homozygous missense TTC12 variant identified in an infertile Pakistani man with severe oligoasthenoteratozoospermia and primary ciliary dyskinesia.

TTC12 is a cytoplasmic and centromere-localized protein that plays a role in the proper assembly of dynein arm complexes in motile cilia in both respiratory cells and sperm flagella. This finding underscores its significance in cellular motility and function. However, the wide role of TTC12 in human spermatogenesis-associated primary ciliary dyskinesia (PCD) still needs to be elucidated. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify potentially pathogenic variants causing PCD and multiple morphological abnormalities of sperm flagella (MMAF) in an infertile Pakistani man. Diagnostic imaging techniques were used for PCD screening in the patient. Real-time polymerase chain reaction (RT‒PCR) was performed to detect the effect of mutations on the mRNA abundance of the affected genes. Papanicolaou staining and scanning electron microscopy (SEM) were carried out to examine sperm morphology. Transmission electron microscopy (TEM) was performed to examine the ultrastructure of the sperm flagella, and the results were confirmed by immunofluorescence staining. Using WES and Sanger sequencing, a novel homozygous missense variant (c.C1069T; p.Arg357Trp) in TTC12 was identified in a patient from a consanguineous family. A computed tomography scan of the paranasal sinuses confirmed the symptoms of the PCD. RT-PCR showed a decrease in TTC12 mRNA in the patient's sperm sample. Papanicolaou staining, SEM, and TEM analysis revealed a significant change in shape and a disorganized axonemal structure in the sperm flagella of the patient. Immunostaining assays revealed that TTC12 is distributed throughout the flagella and is predominantly concentrated in the midpiece in normal spermatozoa. In contrast, spermatozoa from patient deficient in TTC12 showed minimal staining intensity for TTC12 or DNAH17 (outer dynein arms components). This could lead to MMAF and result in male infertility. This novel TTC12 variant not only illuminates the underlying genetic causes of male infertility but also paves the way for potential treatments targeting these genetic factors. This study represents a significant advancement in understanding the genetic basis of PCD-related infertility.

Efficacy of virtual reality for pain relief in medical procedures: a systematic review and meta-analysis.

BACKGROUND: Effective pain control is crucial to optimise the success of medical procedures. Immersive virtual reality (VR) technology could offer an effective non-invasive, non-pharmacological option to distract patients and reduce their experience of pain. We aimed to evaluate the efficacy of Immersive virtual reality (VR) technology in reducing patient's pain perception during various medical procedures by conducting a systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and SIGLE until December 2022 for all randomised clinical trials (RCT) evaluating any type of VR in patients undergoing any medical procedure. We conducted a random effect meta-analysis summarising standardised mean differences (SMD) with 95% confidence intervals (CI). We evaluated heterogeneity using I 2 and explored it using subgroup and meta-regression analyses. RESULTS: In total, we included 92 RCTs (n = 7133 participants). There was a significant reduction in pain scores with VR across all medical procedures (n = 83, SMD - 0.78, 95% CI - 1.00 to - 0.57, I 2 = 93%, p = < 0.01). Subgroup analysis showed varied reduction in pain scores across trial designs [crossover (n = 13, SMD - 0.86, 95% CI - 1.23 to - 0.49, I 2 = 72%, p = < 0.01) vs parallel RCTs (n = 70, SMD - 0.77, 95% CI - 1.01 to - 0.52, I 2 = 90%, p = < 0.01)]; participant age groups [paediatric (n = 43, SMD - 0.91, 95% CI - 1.26 to - 0.56, I 2 = 87%, p = < 0.01) vs adults (n = 40, SMD - 0.66, 95% CI - 0.94 to - 0.39, I 2 = 89%, p = < 0.01)] or procedures [venepuncture (n = 32, SMD - 0.99, 95% CI - 1.52 to - 0.46, I 2 = 90%, p = < 0.01) vs childbirth (n = 7, SMD - 0.99, 95% CI - 1.59 to - 0.38, I 2 = 88%, p = < 0.01) vs minimally invasive medical procedures (n = 25, SMD - 0.51, 95% CI - 0.79 to - 0.23, I 2 = 85%, p = < 0.01) vs dressing changes in burn patients (n = 19, SMD - 0.8, 95% CI - 1.16 to - 0.45, I 2 = 87%, p = < 0.01)]. We explored heterogeneity using meta-regression which showed no significant impact of different covariates including crossover trials (p = 0.53), minimally invasive procedures (p = 0.37), and among paediatric participants (p = 0.27). Cumulative meta-analysis showed no change in overall effect estimates with the additional RCTs since 2018. CONCLUSIONS: Immersive VR technology offers effective pain control across various medical procedures, albeit statistical heterogeneity. Further research is needed to inform the safe adoption of this technology across different medical disciplines.

A homozygous ARMC3 splicing variant causes asthenozoospermia and flagellar disorganization in a consanguineous family.

Male infertility due to asthenozoospermia is quite frequent, but its etiology is poorly understood. We recruited two infertile brothers, born to first-cousin parents from Pakistan, displaying idiopathic asthenozoospermia with mild stuttering disorder but no ciliary-related symptoms. Whole-exome sequencing identified a splicing variant (c.916+1G>A) in ARMC3, recessively co-segregating with asthenozoospermia in the family. The ARMC3 protein is evolutionarily highly conserved and is mostly expressed in the brain and testicular tissue of human. The ARMC3 splicing mutation leads to the exclusion of exon 8, resulting in a predicted truncated protein (p.Glu245_Asp305delfs*16). Quantitative real-time PCR revealed a significant decrease at mRNA level for ARMC3 and Western blot analysis did not detect ARMC3 protein in the patient's sperm. Individuals homozygous for the ARMC3 splicing variant displayed reduced sperm motility with frequent morphological abnormalities of sperm flagella. Transmission electron microscopy of the affected individual IV: 2 revealed vacuolation in sperm mitochondria at the midpiece and disrupted flagellar ultrastructure in the principal and end piece. Altogether, our results indicate that this novel homozygous ARMC3 splicing mutation destabilizes sperm flagella and leads to asthenozoospermia in our patients, providing a novel marker for genetic counseling and diagnosis of male infertility.

Citrus psyllid management by collective involvement of plant resistance, natural enemies and entomopathogenic fungi.

Crops face constant threats from insect pests, which can lead to sudden disasters and global famine. One of the most dangerous pests is the Asian citrus psyllid (ACP), which poses a significant threat to citrus plantations worldwide. Effective and adaptive management strategies to combat ACP are always in demand. Plant resistance (PR) is a key element in pest management, playing crucial roles such as deterring pests through antifeedant and repellant properties, while also attracting natural enemies of these pests. One effective and innovative approach is the use of entomopathogenic fungi (EPF) to reduce pest populations. Additionally, other natural enemies play an important role in controlling certain insect pests. Given the significance of PR, EPF, and natural arthropod enemies (NAE), this review highlights the benefits of these strategies against ACP, drawing on successful examples from recent research. Furthermore, we discuss how EPF can be effectively utilized in citrus orchards, proposing strategies to ensure its efficient use and safeguard food security in the future.

Nanocellulose-Based Hybrid Scaffolds for Skin and Bone Tissue Engineering: A 10-Year Overview.

Cellulose, the most abundant polymer on Earth, has been widely utilized in its nanoform due to its excellent properties, finding applications across various scientific fields. As the demand for nanocellulose continues to rise and its ease of use becomes apparent, there has been a significant increase in research publications centered on this biomaterial. Nanocellulose, in its different forms, has shown tremendous promise as a tissue engineered scaffold for regeneration and repair. Particularly, nanocellulose-based composites and scaffolds have emerged as highly demanding materials for both soft and hard tissue engineering. Medical practitioners have traditionally relied on collagen and its analogue, gelatin, for treating tissue damage. However, the limited mechanical strength of these biopolymers restricts their direct use in various applications. This issue can be overcome by making hybrids of these biopolymers with nanocellulose. This review presents a comprehensive analysis of the recent and most relevant publications focusing on hybrid composites of collagen and gelatin with a specific emphasis on their combination with nanocellulose. While bone and skin tissue engineering represents two areas where a majority of researchers are concentrating their efforts, this review highlights the use of nanocellulose-based hybrids in these contexts.

Investigating the effects of tauroursodeoxycholic acid (TUDCA) in mitigating endoplasmic reticulum stress and cellular responses in Pak choi.

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) within plant cells due to unfavourable conditions leads to ER stress. This activates interconnected pathways involving reactive oxygen species (ROS) and unfolded protein response (UPR), which play vital roles in regulating ER stress. The aim of this study is to investigate the underlying mechanisms of tunicamycin (TM) induced ER stress and explore the potential therapeutic applications of tauroursodeoxycholic acid (TUDCA) in mitigating cellular responses to ER stress in Pak choi (Brassica campestris subsp. chinensis). The study revealed that ER stress in Pak choi leads to detrimental effects on plant morphology, ROS levels, cellular membrane integrity, and the antioxidant defence system. However, treatment with TUDCA in TM-induced ER stressed Pak choi improved morphological indices, pigment contents, ROS accumulation, cellular membrane integrity, and antioxidant defence system restoration. Additionally, TUDCA also modulates the transcription levels of ER stress sensors genes, ER chaperone genes, and ER-associated degradation (ERAD) genes during ER stress in Pak choi. Furthermore, TUDCA has demonstrated its ability to alleviate ER stress, stabilize the UPR, reduce oxidative stress, prevent apoptosis, and positively influence plant growth and development. These results collectively comprehend TUDCA as a promising agent for mitigating ER stress-induced damage in Pak choi plants and provide valuable insights for further research and potential applications in crop protection and stress management.

Harnessing Phytohormones: Advancing Plant Growth and Defence Strategies for Sustainable Agriculture.

Phytohormones, pivotal regulators of plant growth and development, are increasingly recognized for their multifaceted roles in enhancing crop resilience against environmental stresses. In this review, we provide a comprehensive synthesis of current research on utilizing phytohormones to enhance crop productivity and fortify their defence mechanisms. Initially, we introduce the significance of phytohormones in orchestrating plant growth, followed by their potential utilization in bolstering crop defences against diverse environmental stressors. Our focus then shifts to an in-depth exploration of phytohormones and their pivotal roles in mediating plant defence responses against biotic stressors, particularly insect pests. Furthermore, we highlight the potential impact of phytohormones on agricultural production while underscoring the existing research gaps and limitations hindering their widespread implementation in agricultural practices. Despite the accumulating body of research in this field, the integration of phytohormones into agriculture remains limited. To address this discrepancy, we propose a comprehensive framework for investigating the intricate interplay between phytohormones and sustainable agriculture. This framework advocates for the adoption of novel technologies and methodologies to facilitate the effective deployment of phytohormones in agricultural settings and also emphasizes the need to address existing research limitations through rigorous field studies. By outlining a roadmap for advancing the utilization of phytohormones in agriculture, this review aims to catalyse transformative changes in agricultural practices, fostering sustainability and resilience in agricultural settings.

Persistent organic pollutant exposure as a risk factor of gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Findings related to the association between persistent organic pollutants (POPs) and gestational diabetes mellitus (GDM) are inconclusive. OBJECTIVES: To estimate the strength of the association between POP exposure and GDM in a systematic review with meta-analysis. SEARCH STRATEGY: MEDLINE, Scopus and Web of Science were searched until July 2023. SELECTION CRITERIA: Cohort and case-control studies analysing the association between POPs and GDM. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias using the Quality in Prognosis Studies scale (QUIPS). Standardised mean differences were pooled using random-effect models. MAIN RESULTS: Sixteen articles including 12 216 participants were selected. The risk of bias was high in four articles (25%), moderate in 11 (68.75%) and low in one (6.25%). Small mean difference between GDM cases and controls was observed for PFHpA (0.26, 95% confidence interval [CI] 0.1-0.35, I2 = 0.0%), PCB180 (0.37, 95% CI 0.19-0.56; I2 = 25.3%), BDE47 (0.23, 95% CI 0.0-0.45, I2 = 0%), BDE99 (0.36, 95% CI 0.14-0.59; I2 = 0%), BDE100 (0.42, 95% CI 0.19-0.64; I2 = 0%) and HCB (0.22, 95% CI 0.01-0.42, I2 = 39.6%). No considerable difference was observed for the rest of POPs. CONCLUSION: Small mean differences between GDM cases and controls were observed for some POPs. However, evidence shows mostly moderate quality and results were heterogeneous. Improved research methodology is needed to assess POPs and GDM risk.

Quantifying the association of sperm DNA fragmentation with assisted reproductive technology outcomes: An umbrella review.

BACKGROUND: Systematic reviews and meta-analyses are instrumental in shaping clinical practice. However, their findings can sometimes be marred by discrepancies and potential biases, thereby diluting the strength of the evidence presented. Umbrella reviews serve to comprehensively assess and synthesise these reviews, offering a clearer insight into the quality of the evidence presented. In the context of the relationship between sperm DNA fragmentation (SDF) and assisted conception outcomes, there is a divergence in the literature. Some reviews suggest a clear cause-and-effect linkage, whereas others present conflicting or inconclusive results. OBJECTIVES: In this umbrella review we aimed to synthesise the evidence collated in systematic reviews and meta-analyses summarising the association of SDF with assisted reproductive technology (ART) outcomes. SEARCH STRATEGY: After preregistration (https://doi.org/10.17605/OSF.IO/6JHDP), we performed a comprehensive search of the PubMed, Scopus, Cochrane Library, Web of Science and Embase databases. We conducted a search for systematic reviews on the association between SDF and ART without any restrictions on language or publication date. SELECTION CRITERIA: Systematic reviews and meta-analyses assessing the association between SDF and ART outcomes were eligible. DATA COLLECTION AND ANALYSIS: We assessed the quality of the included reviews using AMSTAR 2 and ROBIS, and determined the degree of overlap of primary studies between reviews estimating the corrected covered area (CCA), adjusted for structural missingness. We evaluated the most recent reviews assessing the association of SDF with live birth, pregnancy, miscarriage, implantation, blastulation and fertilisation. The synthesis of evidence was harmonised across all included quantitative syntheses, re-estimating the odds ratio (eOR) in random-effects meta-analyses with 95% confidence intervals (95% CIs) and 95% prediction intervals (95% PIs). We categorised the evidence strength into convincing, highly suggestive, suggestive, weak or nonsignificant, according to the meta-analysis re-estimated P-value, total sample size, I2 statistic for heterogeneity, small study effect, excess significance bias and the largest study significance. MAIN RESULTS: We initially captured and screened 49 332 records. After excluding duplicate and ineligible articles, 22 systematic reviews, 15 of which were meta-analyses, were selected. The 22 reviews showed a moderate degree of overlap (adjusted CCA 9.2%) in their included studies (overall n = 428, with 180 unique studies). The 15 meta-analyses exhibited a high degree of overlap (adjusted CCA = 13.6%) in their included studies (overall n = 274, with 118 unique studies). AMSTAR 2 categorised the quality of evidence in 18 reviews as critically low and the quality of evidence in four reviews as low. ROBIS categorised all the reviews as having a high risk of bias. The re-estimated results showed that the association of SDF with live birth was weak in one and nonsignificant in four meta-analyses. Similarly, the association of SDF with pregnancy, miscarriage, implantation, blastulation and fertilisation was also weak or nonsignificant. The association of high SDF with different ART outcomes was also weak or nonsignificant for different interventions (IVF, ICSI and IUI) and tests. CONCLUSIONS: This umbrella review did not find convincing or suggestive evidence linking SDF with ART outcomes. Caution should be exercised in making any claims, policies or recommendations concerning SDF.

Evaluation of pediatric patients for intestinal transplantation in the modern era.

OBJECTIVES: To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center. METHODS: Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression. RESULTS: Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005). CONCLUSIONS: Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.

Multifunctional role of nanoparticles for the diagnosis and therapeutics of cardiovascular diseases.

The increasing burden of cardiovascular disease (CVD) remains responsible for morbidity and mortality worldwide; their effective diagnostic or treatment methods are of great interest to researchers. The use of NPs and nanocarriers in cardiology has drawn much interest. The present comprehensive review provides deep insights into the use of current and innovative approaches in CVD diagnostics to offer practical ways to utilize nanotechnological interventions and the critical elements in the CVD diagnosis, associated risk factors, and management strategies of patients with chronic CVDs. We proposed a decision tree-based solution by discussing the emerging applications of NPs for the higher number of rules to increase efficiency in treating CVDs. This review-based study explores the screening methods, tests, and toxicity to provide a unique way of creating a multi-parametric feature that includes cutting-edge techniques for identifying cardiovascular problems and their treatments. We discussed the benefits and drawbacks of various NPs in the context of cost, space, time and complexity that have been previously suggested in the literature for the diagnosis of CVDs risk factors. Also, we highlighted the advances in using NPs for targeted and improved drug delivery and discussed the evolution toward the nano-cardiovascular potential for medical science. Finally, we also examined the mixed-based diagnostic approaches crucial for treating cardiovascular disorders, broad applications and the potential future applications of nanotechnology in medical sciences.

Co-metabolic degradation and metabolite detection of hexabromocyclododecane by Shewanella oneidensis MR-1.

Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant; however, it is a persistent organic pollutant as well as affects the human thyroid hormones and causes cancer. However, the degradation of HBCD has received little attention from researchers. Due to its bioaccumulative and hazardous properties, an appropriate strategy for its remediation is required. In this study, we investigated the biodegradation of HBCD using Shewanella oneidensis MR-1 under optimized conditions. The Box-Behnken design (BBD) was implemented for the optimization of the physical degradation parameters of HBCD. S. oneidensis MR-1 showed the best degradation performance at a temperature of 30 °C, pH 7, and agitation speed of 115 rpm, with an HBCD concentration of 1125 µg/L in mineral salt medium (MSM). The strain tolerated up to 2000 µg/L HBCD. Gas chromatography-mass spectrometry analysis identified three intermediates, including 2-bromo dodecane, 2,7,10-trimethyldodecane, and 4-methyl-1-decene. The results provide an insightful understanding of the biodegradation of HBCD by S. oneidensis MR-1 under optimized conditions and could pave the way for further eco-friendly applications. KEY POINTS: • HBCD biodegradation by Shewanella oneidensis • Optimization of HBCD biodegradation by the Box-Behnken analysis • Identification of useful metabolites from HBCD degradation.

Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers.

A series of 3-substituted and 3,5-disubstituted rhodanine-based derivatives were synthesized from 3-aminorhodanine and examined for α-amylase inhibitory, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities in vitro. These derivatives displayed significant α-amylase inhibitory potential with IC50 values of 11.01-56.04 µM in comparison to standard acarbose (IC50 = 9.08 ± 0.07 µM). Especially, compounds 7 (IC50 = 11.01 ± 0.07 µM) and 8 (IC50 = 12.01 ± 0.07 µM) showed highest α-amylase inhibitory activities among the whole series. In addition to α-amylase inhibitory activity, all compounds also demonstrated significant scavenging activities against DPPH and ABTS radicals, with IC50 values ranging from 12.24 to 57.33 and 13.29-59.09 µM, respectively, as compared to the standard ascorbic acid (IC50 = 15.08 ± 0.03 µM for DPPH; IC50 = 16.09 ± 0.17 µM for ABTS). These findings reveal that the nature and position of the substituents on the phenyl ring(s) are crucial for variation in the activities. The structure-activity relationship (SAR) revealed that the compounds bearing an electron-withdrawing group (EWG) at para substitution possessed the highest activity. In kinetic studies, only the km value was changed, with no observed changes in Vmax, indicating a competitive inhibition. Molecular docking studies revealed important interactions between compounds and the α-amylase active pocket. Further advanced research needs to perform on the identified compounds in order to obtain potential antidiabetic agents.

The role of microbial partners in heavy metal metabolism in plants: a review.

Heavy metal pollution threatens plant growth and development as well as ecological stability. Here, we synthesize current research on the interplay between plants and their microbial symbionts under heavy metal stress, highlighting the mechanisms employed by microbes to enhance plant tolerance and resilience. Several key strategies such as bioavailability alteration, chelation, detoxification, induced systemic tolerance, horizontal gene transfer, and methylation and demethylation, are examined, alongside the genetic and molecular basis governing these plant-microbe interactions. However, the complexity of plant-microbe interactions, coupled with our limited understanding of the associated mechanisms, presents challenges in their practical application. Thus, this review underscores the necessity of a more detailed understanding of how plants and microbes interact and the importance of using a combined approach from different scientific fields to maximize the benefits of these microbial processes. By advancing our knowledge of plant-microbe synergies in the metabolism of heavy metals, we can develop more effective bioremediation strategies to combat the contamination of soil by heavy metals.

Prevalence of obstetric violence in high-income countries: A systematic review of mixed studies and meta-analysis of quantitative studies.

INTRODUCTION: Obstetric violence, or mistreatment of women in obstetric care, can have severe consequences such as fear of future childbirth, post-traumatic stress disorder, and depression. MATERIAL AND METHODS: The primary objective was to estimate the prevalence of obstetric violence in high-income countries. The secondary objective was to extract the main domains of obstetric violence perceived by women from qualitative studies. Following prospective registration (PROSPERO CRD42023468570), PubMed, Web of Science, Scopus, CINAHL, Embase, and Cochrane Library were searched with no restrictions. Included studies were cross-sectional, cohort, mixed methods, and qualitative studies based on populations from high-income countries. The review was conducted by two independent reviewers. Risk of bias was assessed. Rates of obstetric violence were pooled using random effects model, computing 95% confidence intervals (CI) and assessing heterogeneity using I2 statistic. Funnel plots and Egger's test were used to detect potential reporting biases and small-study effects. RESULTS: Of the 1821 records screened, 25 studies were included: 14 quantitative and 2 mixed methods studies, comprising 60 987 women, and 9 qualitative studies were included, comprising an additional 4356 women. 81.25% of quantitative studies, including the quantitative component of the mixed methods studies, were considered satisfactory or better regarding risk of bias. The prevalence of obstetric violence was overall 45.3% (95% CI 27.5-63.0; I2 = 100.0%). The prevalence of specific forms of mistreatment was also estimated. Lack of access to analgesia was 17.3% (95% CI 6.9-27.7; I2 = 99.7%). Ignored requests for help was 19.2% (95% CI 11.7-26.6; I2 = 99.0%). Shouting and scolding 19.7% (95% CI 13.0-26.4; I2 = 98.7%). The use of fundal pressure during the second stage of labor (Kristeller maneuver) was 30.3% (95% CI 22.1-38.5; I2 = 97.6%). There was no funnel asymmetry. Lack of information and/or consent were the most frequent domains extracted from the qualitative articles and the qualitative component of the mixed methods studies. CONCLUSIONS: The results demonstrate that obstetric violence is a prevalent problem that women in high-income countries experience. Lack of information and/or consent were the domains most frequently described in the qualitative studies and the qualitative component of the mixed methods studies.

Anti-Acanthamoebic effects of silver-conjugated tetrazole nanoparticle.

Tetrazoles are five-membered ring aromatic heterocyclic molecules that consist of one carbon and four nitrogen atoms. Several tetrazole-based drugs have shown promising activities against bacteria, fungi, asthma, cancer, hypertension etc. The overall aim of this study was to determine anti-Acanthamoebic properties of tetrazoles and tetrazole-conjugated silver nanoparticles. Tetrazole-conjugated silver nanoparticles were synthesized and confirmed using ultraviolet-visible spectrometry, Dynamic light scattering, and Fourier-transform infrared spectroscopy. Using amoebicidal, encystment, and excystment assays, the findings revealed that tetrazoles exhibited antiamoebic properties and these effects were enhanced when conjugated with silver nanoparticles. Importantly, conjugation with silver nanoparticles inhibited parasite-mediated human cell death in vitro, as measured by lactate dehydrogenase release, but it reduced toxic effects of drugs alone on human cells. Overall, these results showed clearly that tetrazoles exhibit potent antiamoebic properties which can be enhanced by conjugation with silver nanoparticles and these potential in the rational development of therapeutic interventions against parasitic infections such as keratitis and granulomatous amoebic encephalitis due to pathogenic Acanthamoeba.

Production Technologies for Recombinant Antibodies: Insights into Eukaryotic, Prokaryotic, and Transgenic Expression Systems.

Recombinant antibodies, a prominent class of recombinant proteins, are witnessing substantial growth in research and diagnostics. Recombinant antibodies are being produced employing diverse hosts ranging from highly complex eukaryotes, for instance, mammalian cell lines (and insects, fungi, yeast, etc.) to unicellular prokaryotic models like gram-positive and gram-negative bacteria. This review delves into these production methods, highlighting approaches like antibody phage display that employs bacteriophages for gene library creation. Recent studies emphasize monoclonal antibody generation through hybridoma technology, utilizing hybridoma cells from myeloma and B-lymphocytes. Transgenic plants and animals have emerged as sources for polyclonal and monoclonal antibodies, with transgenic animals preferred due to their human-like post-translational modifications and reduced immunogenicity risk. Chloroplast expression offers environmental safety by preventing transgene contamination in pollen. Diverse production technologies, such as stable cell pools and clonal cell lines, are available, followed by purification via techniques like affinity chromatography. The burgeoning applications of recombinant antibodies in medicine have led to their large-scale industrial production.

Morpometric and molecular characterization of Surguli goat through CO1 gene in district Kohat.

The present study was designed with the aim to study morphometric characterization as well as phylogeny and diversity of the local Surguli goat at their breeding tract district Kohat through mitochondrial DNA region, i.e., Cytochrome C Oxidase Subunit One (CO1) gene. Morphometric data and blood samples were collected from thirty (30) pure goats. Morphometric analysis showed that sex had significant effect (p < 0.05) on body weight, body length, hearth girth and horn length while no significant effect (p > 0.05) was observed for other characteristics. The results also indicated that age had significant effect (p < 0.05) on height at rump, ear length, horn length and tail length while no significant effect (p > 0.05) was observed for other characteristics. The phylogenetic analysis through CO1 nucleotide sequences within nucleotide range 1-767 showed nine polymorphic sites segregating into eight haplotypes. The mean intraspecific diversity and mean interspecific diversity were calculated as 0.23 and 2.36%, respectively. Phylogenetic tree revealed that Capra Ibex and native Surguli goat have common ancestors. The morphometric and molecular results obtained from the present study can be exploited as a selection tool for breeding and overall improvement.