Vibrational spectroscopy of interstellar PAHs: 1-cyanonaphthalene and 2-cyanonaphthalene.

In this work, we present a comprehensive experimental and theoretical study of the vibrational spectra of PAH molecules recently detected in the interstellar medium: 1-cyanonaphthalene and 2-cyanonaphthalene. The room temperature IR spectra of 1- and 2-cyanonaphthalene in the region 100-3100 cm-1 and their vibrational Raman spectra in the region 35-3100 cm-1 are reported here for the first time. A detailed spectral analysis is carried out using quantum chemical calculations employing the DFT methodology. Anharmonic corrections using the VPT2 method yield excellent agreement with the experimental spectra. A re-investigation of the vibrational spectrum of the parent molecule: naphthalene validates the experimental and theoretical methods used. A consistent set of assignments is reported for the fundamental bands of 1- and 2-cyanonapththalene. The experimental and theoretical data presented here would be useful inputs for modelling the role of cyanonaphthalene in astrophysical processes.

Bereavement due to COVID-19 pandemic among school-going adolescents - A cross-sectional study in district Dehradun.

BACKGROUND: Millions of people lost their loved ones due to the COVID-19 pandemic; this dire situation had an impact on almost every aspect of the daily life of every person. However, most of the individuals adapted to their losses nearly 2-10% of the population experienced dysfunctional grief in which adolescents were also affected. Aims and Objectives: Prime objective of the study was to assess dysfunctional grief due to loss from COVID-19 Pandemic among adolescents and to find out the coping strategies used by them to overcome this grief. MATERIALS AND METHODS: The study was conducted among school-going adolescents of District Dehradun. A pre-designed, pre-tested, self-administered, semi-structured questionnaire including socio-demographic details, COVID-19-related questions and Pandemic Grief Scale (Cronbach alpha-0.77) was used in the offline survey. RESULTS: Out of 690 study participants, a total of 151 (21.8%) adolescents lost their loved ones due to the COVID-19 pandemic. Of these, 9.93% were facing dysfunctional grief due to their loss. To overcome this grief, coping strategies used by study participants were mainly phone and internet usage (78%) followed by watching TV (73.8%) and sleeping (68.1%). CONCLUSION: Adolescents who experienced loss and were grieved are more at high risk of developing psychological disorders, particularly depression, anxiety, and physical illness, that might affect their education and overall development. Though to tackle the mental health crisis in the country Tele-Mental Health Assistance and Networking Across States (Tele-MANAS) has been initiated, still there is a lack of clarity regarding the structure and range of services provided by Tele-MANAS centers set up under the National Tele-Mental Health Program (NTMHP). Timely intervention and research to take solid steps to diminish the potential adverse effects of bereavement on adolescents' mental health is necessary.

Tuning Nanographene-Enhanced Raman Scattering for Rapid Label-Free Detection of Amino Acids.

The rapid and sensitive detection of amino acids is important not only for fundamental studies but also for the establishment of a healthy society. However, conventional detection methods have been hampered by the difficulties of low sensitivity, long sampling and detection times, and expensive operation and instruments. Here, we report the plasma engineering of bioresource-derived graphene quantum dots (GQDs) as surface-enhanced Raman scattering (SERS)-active materials for the rapid and sensitive detection of amino acids. Surface-functionalized GQDs with tuned structures and band gaps were synthesized from earth-abundant bioresources by using reactive microplasmas under ambient conditions. Detailed microscopy and spectroscopy studies indicate that the SERS properties of the synthesized GQDs can be tuned by controlling the band gaps of synthesized GQDs. The plasma-synthesized metal-free GQDs with surface functionalities showed improved SERS properties for rapid amino acid detection with low detection limits of 10-5 M for tyrosine and phenylalanine. Theoretical calculations suggest that charge transfer between GQDs and amino acids can enhance the SERS response of the GQDs. Our work provides insights into the controlled engineering of SERS-active nanographene-based materials using the plasma-enhanced method.

Physiological and molecular insights into the alternate bearing in mango (Mangifera indica L.) using next-generation sequencing approaches.

India's mango productivity is hindered by many factors but more importantly due to limited understanding of the genomic complexities behind regular bearing habit. This study is the first to quantify carbohydrate fractions, protein content, and macro and micronutrient storage pools, their transportation, and contributions to regular 'Totapuri' and alternate bearer 'Bombay Green' mango varieties during the 'off' year. Deep RNA sequencing was used to assess gene expression dynamics between buds and flowers of these varieties. Differential pathway analysis showed the greatest number of differentially expressed genes in metabolic processes (1377), followed by oxido-reductase (879), hormone (80), oxidative stress (77), starvation (39), alternate bearing (8), flowering (3), meristem (3), and cellular component (2) pathways. In silico analysis showed that among 15 genes, twelve genes up-regulated in Totapuri and three in Bombay Green, confirmed by qRT-PCR. Additionally, 202 SNPs were identified in 32 alternate bearing-related genes. The study confirmed the reproductive bud's strong ability to import sugars, protein, and starch in the regular bearer variety, enhancing flowering and fruiting during off years. The mineral nutrients and biochemical constituent of the bud and leaf tissue in contrasting genotypes, showed the potential role for regular bearing in mango.

A Pilot Study in Adapting the Chronic Care Model to Address Shortage of Child and Adolescent Psychiatry.

There is a nationwide shortage of child and adolescent psychiatrists. This, combined with the mental health crisis caused by the coronavirus 2019 pandemic has lead to low access to care for many individuals. Child Psychiatry Access Programs have been developed to address this need, but we believe they are not sufficient to care for complex cases. We propose that the Chronic Care Model can address these issues by providing, more longitudinal and and faster access to mental health care for patients. Our pilot study had 50 children and adolescent participants in our clinic model, which included the use of trainees supervised by an attending. We found that the mean wait time to appointment with a child and adolescent psychiatrist was 13.54 ± 14.8 days, which is significantly shorter by that reported by other studies. We believe our model clinic may be helpful in a variety of settings and want to share it with other psychiatrists.

Long-term Visual Outcomes in Patients With Idiopathic Macular Hole Surgery.

BACKGROUND AND OBJECTIVE: This study assesses long-term outcomes following surgical repair of idiopathic full-thickness macular holes (FTMHs) in patients with at least 5 years of postoperative follow-up. PATIENTS AND METHODS: A retrospective study evaluated patients diagnosed with idiopathic FTMH who received surgical repair at a single tertiary center with at least 5 years of postoperative follow-up. Data collection included demographic and preoperative characteristics along with macular hole structural integrity as determined by spectral-domain optical coherence tomography (OCT). Functional and structural improvement were assessed by collection of visual acuity and findings on OCT at determined time points until 9 years of follow-up. RESULTS: The study comprised 90 eyes of 80 patients with a mean age of 67.2 ± 6.8 years, with an average postoperative follow-up of 80.8 ± 17.4 months (range 54 to 130 months). The mean macular hole diameter was 239.7 µm ± 92.2. Macular hole reoperation occurred in four eyes (4%) at a mean duration of 5.5 ± 6 months (range 0.3 to 13 months). Over the study duration, ellipsoid zone (EZ) integrity was maintained in 67.8% of eyes, with an absence of intraretinal fluid (IRF) in 96% on final OCT. The preoperative mean Early Treatment Diabetic Retinopathy Study (ETDRS) best visual acuity (BVA) of 51 improved to a mean BVA of 76 at 5 years postoperatively, with an average gain of 24 letters at one year that remained stable over 5 years (P < 0.05). Eight years after surgical repair, more than 80% of patients achieved a BVA > 65. CONCLUSIONS: Vitreoretinal surgery for idiopathic FTMH resulted in successful hole closure and sustained visual acuity improvement over long-term follow-up. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Case report: One-stage craniectomy and cranioplasty digital workflow for three-dimensional printed polyetheretherketone implant for an extensive skull multilobular osteochondosarcoma in a dog.

Objective: To report a digital workflow for use and long-term outcome of cranioplasty with a 3D-printed patient-specific Polyetheretherketone (PEEK) implant in a 12-y-old German Shepherd dog after surgical removal of an extensive occipital bone multilobular osteochondrosarcoma (MLO). Study design: Retrospective case report. Animal: A 12-year-old neutered female German Shepherd dog was presented with facial deformity, blindness, tetraparesis, and ataxia. Magnetic resonance imaging (MRI) and computed tomography (CT) identified a large skull-based mass extending extra-and intracranially with severe compression of the cerebellum and occipital lobes of the cerebrum. Methods: One-stage decompressive craniectomy using virtual surgical planned 3D-printed craniotomy cutting guides and the Misonix BoneScalpel® and reconstruction with a patient-specific 3D-printed PEEK cranial implant. Results: 3D-printed craniectomy cutting guides allowed an adequate fit of the cranial implant to the original skull. Misonix BoneScalpel® allowed performing a safe and extensive craniectomy. Postoperative CT (8 weeks after surgery) confirmed the PEEK cranial implant to be in place and without implant rejection. Clinically, the neurological examination identified only a right-hind limb delay in proprioception 8 weeks postoperatively, which remained unchanged at 18 months after surgery. Adjunctive treatment included metronomic chemotherapy. Eighteen months after surgery the dog passed away for reasons unrelated to the MLO, no implant-related complications were reported. Conclusion: 3D-printed craniectomy cutting guides, patient-specific PEEK cranial implant, and metronomic chemotherapy can lead to a successful long-term outcome in dogs with extensive skull MLO. Clinical significance: PEEK is an alternative biomaterial that can be used successfully for skull reconstruction.

Revolutionizing Skin Cancer Treatment: The Rise of PD-1/PDL-1 and CTLA-4 as Key Therapeutic Targets.

Skin cancer is a significant health concern, affecting millions of individuals globally on an annual basis. According to data from the World Health Organization, it stands as the most prevalent form of cancer within the white population. Current treatments for skin cancer typically involve a combination of chemotherapy, radiation therapy, and surgery. However, these methods often come with drawbacks, such as side effects and potential scarring. Therefore, there is a growing need for alternative treatments that can offer effective results with fewer adverse effects, driving ongoing research in skin cancer therapy. The advancement of immune checkpoint inhibitors has been facilitated by a more profound comprehension of the interplay between tumors and the immune system, along with the regulatory mechanisms governing T-cells. As cancer treatment continues to evolve, immunotherapy is emerging as a powerful strategy, leading to a growing interest in the role of immunological checkpoints in skin cancer. Various types of immune checkpoints and their expression, including PD-1, PDL-1, CTLA-4, lymphocyte activation gene 3, and B7-H3, along with their blockers and monoclonal antibodies, have been established for various cancers. PD-1, PDL-1, and CTLA-4 are crucial immune system regulators, acting as brakes to prevent T-- cell overactivation and potential autoimmunity. However, tumors can exploit these checkpoints to evade immune detection. Inhibiting these immune checkpoints can enhance the body's ability to recognize and attack cancer cells. This review focuses on the characteristics of PD-1, PDL-1, and CTLA-4 immune checkpoints, their mechanism of action, and their role in skin cancer. Additionally, it summarizes the ongoing clinical trials sponsored or conducted by various pharmaceutical companies and provides insights into the latest patent data.

Role of PD-1 in Skin Cancer: Molecular Mechanism, Clinical Applications, and Resistance.

Skin cancer is a widespread worldwide health concern, manifesting in many subtypes such as squamous cell carcinoma, basal cell carcinoma, and melanoma. Although all these types occur frequently, they generally lack the possibility of being cured, emphasizing the importance of early discovery and treatment. This comprehensive study explores the role of programmed cell death protein 1 (PD-1) in skin cancer, focusing on its molecular mechanisms in immune regulation and its critical role in tumor immune evasion, while also clarifying the complexities of immune checkpoints in cancer pathogenesis. It critically evaluates the clinical applications of PD-1 inhibitors, spotlighting their therapeutic potential in treating skin cancer, while also addressing the significant challenge of resistance. This work further discusses the evolution of resistance mechanisms against PD-1 inhibitors and suggests potential approaches to mitigate these issues, thereby enhancing the effectiveness of these therapies. The study further highlights the current state of PD-1 targeted therapies and sets the stage for future research aimed at optimizing these treatments for better clinical outcomes in skin cancer.

Long-term visual outcomes and fluid compartment changes in limited-early versus early response to anti-VEGF treatment for diabetic macular edema.

OBJECTIVE: This study assessed best visual acuity (BVA) and central subfield thickness (CST) outcomes for LER (limited early responder) and ER (early responder) patients at 24 and 36 months. DESIGN: Retrospective chart review PARTICIPANTS: One-hundred and twelve patients characterized at 3 months after their first anti-VEGF injections as either LER if they met the anatomic criteria (aLER = CST reductions ≤ 10%), visual criteria (vLER = ETDRS letter gains < 5 letter), or both (cLER). All other patients were classified as ER (aER/vER/cER). METHODS: Variables collected include CST and ETDRS letters at baseline, 3, 24, and 36 months following injections, comorbidities, smoking status, demographics, baseline systemic factors, and the type and quantity of anti-VEGF injections. Analyses were performed using Welch's t-test, multivariable linear and multivariable logistic regression. RESULTS: BVA changes from 3 months were significant between cLER versus cER and vLER versus vER groups (p < 0.05). There was a greater decrease in mean BVA from 3 months to 36 months in the cER group compared to the cLER group. Alternatively, mean BVA decreased in the vER cohort, while the vLER cohort slightly increased. CST changes from 3 months were statistically significant (p < 0.01) between all LER and ER groups with LER groups showing greater reductions compared to ER counterparts. BVA and CST changes from baseline to 24 and 36 months were not significant after controlling for baseline differences between LER and ER groups. CONCLUSION: Results highlight the value of long-term anti-VEGF treatment and the need to further explore options that may lead to continued BVA improvements beyond 3 months.

The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Diabetic Retinopathy at a Tertiary Care Center.

Objective: The potential association between diabetic retinopathy (DR) worsening and glucagon-like peptide-1 receptor agonists (GLP-1RA) has affected therapeutic management of diabetic patients but remains controversial. This study compared rates of DR development or progression in patients on GLP-1RA to those on SGLT-2 inhibitors (SGLT-2I). Design: Retrospective cohort study. Subjects: Nine hundred eighty-one patients with diabetes mellitus taking GLP-1RA or SGLT-2I, the latter serving as controls, between 2012 and 2023. Methods: Patients were one-to-one greedy matched by propensity scores on race/ethnicity, age, smoking status, baseline body mass index and hemoglobin A1c %, type of diabetes mellitus, baseline DR status and history of DR procedures, duration of drug use, whether they had taken both drug types, and change in hemoglobin A1c % after 1 year on the drug. Main Outcome Measures: The primary outcome was clinical DR development or progression (termed "worsening") detected by International Classification of Diseases (ICD), 10th edition codes, confirmed by manual review, on GLP-1RA compared with SGLT-2I after propensity score matching. Secondary outcomes included DR worsening indicated by need for procedures due to complications, and time-to-first DR worsening event. Results: The study included 692 GLP-1RA users and 289 SGLT-2I users. The mean follow-up periods for GLP-1RA versus SGLT-2I use were 1.54 (standard deviation [SD] 1.82) years and 1.38 (SD 1.56) years, respectively. The rates of clinical worsening were 2.3% and 2.8%, respectively. After propensity score matching, an association was not identified between GLP1-RA and DR worsening neither clinically by ICD-10 codes (odds ratio [OR] = 0.33, 95% confidence interval [CI]: 0.11-1.03) nor by indication for procedures (OR = 0.50, 95% CI 0.13-2.00). Time-to-first DR worsening did not differ between the groups in Kaplan-Meier analysis. The most common type of clinical worsening event for both drug types was vitreous hemorrhage (43.7% and 50% of worsening events in GLP-1RA and SGLT-2I users, respectively). The most common DR procedure indicated was anti-VEGF injections (34% and 35% of GLP-1RA and SGLT-2I events, respectively). Conclusions: Diabetic retinopathy worsening, either clinically or by procedures, was not associated with GLP-1RA compared with SGLT-2I, both before and after propensity score matching on all analyses, including time-to-first worsening event. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Hole in the Heart, a Hole in the Defenses: A Case of Pseudomonas Endocarditis.

Infective endocarditis (IE) is a rare but serious infection of the cardiac endothelium. This case report presents a rare instance of left-sided Pseudomonas aeruginosa endocarditis in an immunocompetent patient without traditional risk factors for IE. Pseudomonas endocarditis is uncommon and usually associated with specific factors. The patient in this case was a 30-year-old male with end-stage renal disease, receiving hemodialysis through a tunneled dialysis catheter, who developed a fever. Blood cultures confirmed P. aeruginosa as the causative agent, which prompted the administration of appropriate antibiotics and the removal of the catheter. However, subsequent imaging revealed significant damage to the mitral valve. Despite timely mitral valve replacement and aggressive medical treatment, the patient's condition worsened, and he ultimately succumbed to the infection. This case also emphasizes the necessity of timely diagnosis and intervention. In this patient, by the time it was diagnosed and managed, significant mitral valve damage had already occurred. Therefore, it should be considered a differential diagnosis even in patients with no risk factors and should be managed vigorously. Pseudomonas endocarditis is associated with high mortality, and successful treatment often requires a combination of antipseudomonal antibiotics due to the organism's ability to develop resistance. Surgical intervention, such as valve replacement, is frequently necessary. This case underscores the importance of considering P. aeruginosa infection, even in patients without traditional risk factors for IE. Early diagnosis, appropriate antibiotic therapy, and timely surgical intervention are critical for improving outcomes in Pseudomonas endocarditis cases.

Silkworm-derived carbon nano rods (swCNR) for detection of bismuth ions (Bi3+) in aquatic medium and their antiradical properties.

The extensive utilization of bismuth and its derivatives in many industries, such as chemical, semiconductor, pharmaceutical, and cosmetics, leads to their accumulation in wastewater, posing a risk to both human health and the environment. Carbon nanorods (CNR) are fluorescent nanoparticles with an ability to detect various analytes as sensing probes. This study focuses on the production, structure, and chemical composition characterization of silkworm-derived CNR (swCNR) and their ability to detect bismuth ions (Bi3+) and inhibit radicals. The optimum wavelength for exciting the fluorescence of swCNR was 370 nm, and the resulting emission peak was observed at 436 nm. The prepared swCNR showed static fluorescence quenching mechanism-based sensing of Bi3+ ions with a limit of detection of 175 nM and two linear ranges from 0.5 to 5 µM (R2 = 0.9997) and 10-50 µM (R2 = 0.9995). The swCNR demonstrated high selectivity in detecting Bi3+ ions in the spiked river water samples, thus establishing the swCNR's role as a nano fluorescence probe designed for the selective detection of Bi3+ ions among other metal ions. Favorable results for the antiradical ability of swCNR were obtained against hydroxyl, 2,2 diphenyl-1 picrylhydrazyl, and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals with scavenging percentages of 15, 32, and 90, respectively. The possible applications of swCNR in the environmental and antioxidant sectors are proposed in this study.

Arachidonic acid metabolism regulates the development of retinopathy of prematurity among preterm infants.

Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP), characterized by neovascularization and neuroinflammation leading to blindness. Polyunsaturated fatty acid (PUFA) supplementation is recommended in preterm infants to lower the risk of ROP, however, with no significant improvement in visual acuity. Reasonably, this could be as a result of the non-consideration of PUFA metabolizing enzymes. We hypothesize that abnormal metabolism of the arachidonic acid (AA) pathway may contribute to severe stages of ROP. The present study investigated the AA-metabolizing enzymes in ROP pathogenesis by a targeted gene expression analysis of blood (severe ROP = 70, No/Mild = 56), placenta (preterm placenta = 6, full term placenta = 3), and human primary retinal cell cultures and further confirmed at the protein level by performing IHC in sections of ROP retina. The lipid metabolites were identified by LC-MS in the vitreous humor (VH; severe ROP = 15, control = 15). Prostaglandins D2 (p = 0.02), leukotrienes B5 (p = 0.0001), 11,12-epoxyeicosatrienoic acid (p = 0.01), and lipid-metabolizing enzymes of the AA pathway such as CYP1B1, CYP2C8, COX2, and ALOX15 were significantly upregulated while EPHX2 was significantly (0.04) downregulated in ROP cases. Genes involved in hypoxic stress, angiogenesis, and apoptosis showed increased expression in ROP. An increase in the metabolic intermediates generated from the AA metabolism pathway further confirmed the role of these enzymes in ROP, while metabolites for EPHX2 activity were low in abundance. Inflammatory lipid intermediates were higher compared to anti-inflammatory lipids in VH and showed an association with enzyme activity. Both the placenta of preterm infants who developed ROP and hypoxic retinal cultures showed a reduced expression of EPHX2. These findings suggested a strong involvement of EPHX2 in regulating retinal neovascularization and inflammation. The study results underscore the role of arachidonic acid metabolism in the development of ROP and as a potential target for preventing vision loss among preterm-born infants.

Unraveling popping quality through insights on kernel physical, agro-morphological, and quality traits of diverse popcorn (Zea mays var. everta) inbreds from indigenous and exotic germplasm.

Popcorn is a specialty corn with worldwide popularity as a snack. Despite having great market demand, genetic improvement in popping quality is limited, which is caused by the limited germplasm utilization and narrow genetic base. An assortment of diverse germplasm, their effective characterization, and integration into popcorn breeding pipeline is the foundation for an efficient breeding program. Here, kernel characteristics, popping quality traits, and agro-morphological traits were evaluated across three locations on a diverse panel of 48 popcorn inbreds derived from diverse landraces and populations of exotic and indigenous origin. The variations due to genotypes, locations, and genotype × location interaction were highly significant. The popping quality traits recorded wide variation with a high coefficient of genotypic determination. The kernel dimensions, kernel density, test weight, and grain yield were negatively correlated with popping quality traits. Genotypes with rice-type kernels exhibited better popping quality than pearl-type kernels. Analysis of genotype × location (G×L) interaction identified two target locations for the key popping quality trait, popping expansion volume. PMI-PC-175, PMI-PC-187, PMI-PC-188, and PMI-PC-189 were identified as superior genotypes over checks for desirable popping quality, agronomic performance, and high grain yield. The contrasting inbreds for popping quality and flake shape (mushroom vs. butterfly) can be utilized for developing mapping populations to enhance our understanding of molecular aspects of popping quality traits. Further, the promising inbreds can be utilized in the genetic improvement of popcorn and crossed to develop superior popcorn hybrids. The results suggest a potential opportunity to establish an efficient popcorn breeding program.

Characterization and prevalence of ocular comorbidities and risk of legal blindness across the United States.

BACKGROUND/OBJECTIVES: Vision loss is a top disability in the United States (US). Patients commonly present with multiple ocular diseases, but the extent to which this places them at risk for vision loss, and if sex and race impacts this, is poorly understood. This exploratory analysis evaluated which ocular comorbidities and demographics are at highest risk for visual impairment. SUBJECTS/METHODS: A retrospective cross-sectional study was conducted through the TriNetX Analytics Network, an aggregated network encompassing over 90 million insured and uninsured patients across 50 healthcare organizations from all regions in the US. Patients with diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), glaucoma, and uveitis were included in this study. Ocular diseases and visual impairment were determined through ICD-10 codes. Prevalence and odds ratios were calculated while stratifying by sex and racial demographics. Statistical analyses were completed using RStudio and Excel with 95% confidence intervals calculated. RESULTS: The comorbid conditions with the highest prevalence of visual impairment were uveitis and RVO (39.94%), uveitis and neovascular AMD (37.61%), and uveitis and glaucoma (33.23%). The comorbidity with the highest odds for visual impairment was uveitis and RVO (POR 4.86; 95% CI 4.49, 5.26). Compared to white males, Black and Hispanic males were disproportionately affected by visual impairment across ocular comorbidities. CONCLUSION: This study quantified the prevalence and odds of visual impairment for unilateral and comorbid ocular disease, with the addition of uveitis causing the greatest increase. Black and Hispanic males were disproportionately affected by visual impairment across comorbid conditions.

Targeting Hepatic Cancer Stem Cells (CSCs) and Related Drug Resistance by Small Interfering RNA (siRNA).

Tumor recurrence after curative therapy and hepatocellular carcinoma (HCC) cells' resistance to conventional therapies is the reasons for the worse clinical results of HCC patients. A tiny population of cancer cells with a strong potential for self-renewal, differentiation, and tumorigenesis has been identified as cancer stem cells (CSCs). The discovery of CSC surface markers and the separation of CSC subpopulations from HCC cells have been made possible by recent developments in the study of hepatic (liver) CSCs. Hepatic CSC surface markers include epithelial cell adhesion molecules (EpCAM), CD133, CD90, CD13, CD44, OV-6, ALDH, and K19. CSCs have a significant influence on the development of cancer, invasiveness, self-renewal, metastasis, and drug resistance in HCC, and thus provide a therapeutic chance to treat HCC and avoid its recurrence. Therefore, it is essential to develop treatment approaches that specifically and effectively target hepatic stem cells. Given this, one potential treatment approach is to use particular small interfering RNA (siRNA) to target CSC, disrupting their behavior and microenvironment as well as changing their epigenetic state. The characteristics of CSCs in HCC are outlined in this study, along with new treatment approaches based on siRNA that may be used to target hepatic CSCs and overcome HCC resistance to traditional therapies.

Synergistic impact of Serendipita indica and Zhihengliuella sp. ISTPL4 on the mitigation of arsenic stress in rice.

Arsenic (As) is a highly toxic metal that interferes with plant growth and disrupts various biochemical and molecular processes in plants. In this study, the harmful effects of As on rice were mitigated using combined inoculation of a root endophyte Serendipita indica and an actinobacterium Zhihengliuella sp. ISTPL4. A randomized experiment was conducted, in which rice plants were grown under controlled conditions and As-stressed conditions. The control and treatment groups consisted of untreated and non-stressed plants (C1), treated and non-stressed plants (C2), stressed and untreated plants (T1), and stressed and treated plants (T2). Various phenotypic characteristics such as shoot length (SL), root length (RL), shoot fresh weight (SFW), root fresh weight (RFW), shoot dry weight (SDW), and root dry weight (RDW) and biochemical parameters such as chlorophyll content, protein content, and antioxidant enzymatic activities were evaluated. The activity of various antioxidant enzymes was increased in T2 followed by T1 plants. Furthermore, high concentrations of phytohormones such as ethylene (ET), gibberellic acid (GA), and cytokinin (CK) were found at 4.11 µmol mg-1, 2.53 µmol mg-1, and 3.62 µmol mg-1 of FW of plant, respectively. The results of AAS indicated an increased As accumulation in roots of T2 plants (131.5 mg kg-1) than in roots of T1 plants (120 mg kg-1). It showed that there was an increased As accumulation and sequestration in roots of microbial-treated plants (T2) than in uninoculated plants (T1). Our data suggest that this microbial combination can be used to reduce the toxic effects of As in plants by increasing the activity of antioxidant enzymes such as SOD, CAT, PAL, PPO and POD. Furthermore, rice plants can withstand As stress owing to the active synthesis of phytohormones in the presence of microbial combinations.

Circulating bacterial peptides and linked metabolomic signatures are indicative of early mortality in pediatric cirrhosis.

BACKGROUND: Patients with pediatric cirrhosis-sepsis (PC-S) attain early mortality. Plasma bacterial composition, the cognate metabolites, and their contribution to the deterioration of patients with PC-S to early mortality are unknown. We aimed to delineate the plasma metaproteome-metabolome landscape and identify molecular indicators capable of segregating patients with PC-S predisposed to early mortality in plasma, and we further validated the selected metabolite panel in paired 1-drop blood samples using untargeted metaproteomics-metabolomics by UHPLC-HRMS followed by validation using machine-learning algorithms. METHODS: We enrolled 160 patients with liver diseases (cirrhosis-sepsis/nonsepsis [n=110] and noncirrhosis [n=50]) and performed untargeted metaproteomics-metabolomics on a training cohort of 110 patients (Cirrhosis-Sepsis/Nonsepsis, n=70 and noncirrhosis, n=40). The candidate predictors were validated on 2 test cohorts-T1 (plasma test cohort) and T2 (1-drop blood test cohort). Both T1 and T2 had 120 patients each, of which 70 were from the training cohort. RESULTS: Increased levels of tryptophan metabolites and Salmonella enterica and Escherichia coli-associated peptides segregated patients with cirrhosis. Increased levels of deoxyribose-1-phosphate, N5-citryl-d-ornithine, and Herbinix hemicellulolytic and Leifsonia xyli segregated patients with PC-S. MMCN-based integration analysis of WMCNA-WMpCNA identified key microbial-metabolic modules linked to PC-S nonsurvivors. Increased Indican, Staphylobillin, glucose-6-phosphate, 2-octenoylcarnitine, palmitic acid, and guanidoacetic acid along with L. xyli, Mycoplasma genitalium, and Hungateiclostridium thermocellum segregated PC-S nonsurvivors and superseded the liver disease severity indices with high accuracy, sensitivity, and specificity for mortality prediction using random forest machine-learning algorithm. CONCLUSIONS: Our study reveals a novel metabolite signature panel capable of segregating patients with PC-S predisposed to early mortality using as low as 1-drop blood.

Revolutionizing biomedicine: Aptamer-based nanomaterials and nanodevices for therapeutic applications.

With the progress in two distinct areas of nanotechnology and aptamer identification technologies, the two fields have merged to what is known as aptamer nanotechnology. Aptamers have varying properties in the biomedical field include their small size, non-toxicity, ease of manufacturing, negligible immunogenicity, ability to identify a wide range of targets, and high immobilizing capacity. Nevertheless, aptamers can utilize the distinct characteristics offered by nanomaterials like optical, magnetic, thermal, electronic properties to become more versatile and function as a novel device in diagnostics and therapeutics. This engineered aptamer conjugated nanomaterials, in turn provides a potentially new and unique properties apart from the pre-existing characteristics of aptamer and nanomaterials, where they act to offer wide array of applications in the biomedical field ranging from drug targeting, delivery of drugs, biosensing, bioimaging. This review gives comprehensive insight of the different aptamer conjugated nanomaterials and their utilization in biomedical field. Firstly, it introduces on the aptamer selection methods and roles of nanomaterials offered. Further, different conjugation strategies are explored in addition, the class of aptamer conjugated nanodevices being discussed. Typical biomedical examples and studies specifically, related to drug delivery, biosensing, bioimaging have been presented.