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1.
Cureus ; 16(6): e62454, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39022508

ABSTRACT

Background Oropharyngeal candidiasis (OPC) is a common fungal infection in HIV-seropositive patients. Understanding the spectrum of yeast isolates and their antifungal susceptibility patterns is crucial for effective management. This study aimed to determine the yeast isolates, antifungal susceptibility patterns, and associated factors in HIV-seropositive patients with OPC. Material and methods A prospective observational study was conducted on 350 HIV-seropositive patients attending an Integrated Counselling and Testing Centre (ICTC) at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar. Yeast isolates from oropharyngeal lesions were identified, and their antifungal susceptibility was determined by automated method VITEK 2. Demographic characteristics, highly active antiretroviral therapy (HAART) status, and CD4+ cell count categories were analyzed for associations. Results This study of 350 HIV-seropositive patients revealed that 100 tested positive for Candida, with distinct differences between HAART (n=67) and non-HAART (n=33) groups. HAART patients had a younger age distribution and higher median CD4+ cell counts (350 vs. 250 cells/mm³, U = 175, p < 0.05) compared to non-HAART patients. Candida albicans was the most common species in both groups, but significant variations in species distribution (χ² = 9.23, p < 0.05) and antifungal susceptibility were noted. Specifically, susceptibility differences were significant for flucytosine (χ² = 7.21, p = 0.027) and voriconazole (χ² = 8.64, p = 0.013), emphasizing the influence of HAART on managing immune function and antifungal resistance in HIV patients. Conclusion This study provides insights into the spectrum of yeast isolates and their antifungal susceptibility patterns in HIV-seropositive patients with OPC. The findings emphasize the importance of considering multiple factors, such as Candida species, HAART status, and individual patient characteristics, in treatment decisions. The results will aid in the development of evidence-based management protocols for this vulnerable population. Further research is warranted to explore additional factors influencing antifungal susceptibility and optimize treatment strategies for this patient population.

2.
J Stomatol Oral Maxillofac Surg ; : 101944, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38852622

ABSTRACT

Throat packing is essential in oral and maxillofacial surgeries to prevent blood and tissue debris aspiration, reducing postoperative complications. Traditional oral route methods are often inadequate, especially in severe trismus cases like Oral Submucous Fibrosis (OSMF), TMJ Ankylosis, and post-traumatic conditions due to limited mouth opening. This study introduces a novel technique using a nasopharyngeal airway (NPA) for throat packing. The method involves inserting a hemostatic dressing through an NPA, ensuring minimal invasiveness and effective airway management. Proper positioning is confirmed with a laryngoscope or fiberoptic scope, and the dressing is secured to prevent dislodgement. This technique is easy, reproducible, and less injurious compared to traditional methods. At our center, throat packing via NPA was performed on 35 patients undergoing surgery under general anesthesia, resulting in high satisfaction and no reported complications.

3.
Cureus ; 16(3): e55688, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38595894

ABSTRACT

Background Tuberculosis (TB) remains a global health concern, with India bearing a substantial burden. Paediatric TB, especially extrapulmonary TB (EPTB), presents unique diagnostic challenges due to its paucibacillary nature and the difficulty in obtaining suitable samples in children. Accurate and timely diagnosis is crucial to initiate appropriate treatment and mitigate disease spread. The MPT64 antigen test has shown promise in diagnosing TB, but its performance in paediatric EPTB remains underexplored. This study aimed to evaluate the diagnostic utility of the MPT64 antigen test in paediatric EPTB cases at a tertiary care hospital in India. Methods We conducted a prospective cross-sectional study at the Indira Gandhi Institute of Medical Sciences (IGIMS), a tertiary care hospital in India. A total of 250 paediatric participants, aged 0-18 years, with clinical suspicion of extrapulmonary tuberculosis (EPTB) were included. Diagnostic samples (e.g., tissue biopsies, pus, cerebrospinal fluid (CSF), and lymph node aspirates) were obtained, and tests including microscopy for acid-fast bacilli (AFB), mycobacterial cultures, GeneXpert MTB/RIF assay, and the TB Antigen MPT64 Rapid ICT Kit were performed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the MPT64 antigen test were calculated using culture and GeneXpert as reference standards. Results Among the 250 participants, 34 (13.6%) were confirmed to have EPTB. The MPT64 antigen test demonstrated a sensitivity of 70.6% and specificity of 92.1% in detecting EPTB cases. Mycobacterial cultures had the highest sensitivity (91.2%) and specificity (97.7%). GeneXpert showed a sensitivity of 70.6% and specificity of 93.9%. Overall diagnostic accuracy ranged from 88.7% for acid-fast bacteria (AFB) staining to 96.9% for mycobacterial cultures. The MPT64 antigen test had an area under the curve (AUC) of 0.814, indicating a good diagnostic accuracy. Conclusion The MPT64 antigen test demonstrates promising sensitivity and specificity for diagnosing paediatric EPTB, making it a valuable diagnostic tool, especially in resource-limited settings. However, mycobacterial cultures maintain the highest accuracy. Combining the MPT64 antigen test with other methods may enhance diagnostic capabilities.

4.
Environ Sci Pollut Res Int ; 31(23): 33515-33529, 2024 May.
Article in English | MEDLINE | ID: mdl-38683429

ABSTRACT

Airborne particles (dust pollution) pose a significant threat to both human and plant populations. Plant leaves act as crucial biofilters, capturing significant amounts of air pollution; this characteristic offers a valuable tool to measure local pollution levels and assess individual plant species' ability to intercept and mitigate harmful dust particles. The present study was carried out to asses the effect of responses of various plant species to dust pollution near and around the marble mining site comprising residential site, highway area, and Central University of Rajasthan as control. The anticipated pollution index, air pollution tolerance index (APTI), dust absorption capacity, metal accumulation index (MAI), and biochemical factors were used to evaluate plant responses. Azadirachta indica A. Juss. demonstrated the highest (29.0) and Vachellia nilotica L. showed lowest (5.6) APTI, respectively. A. indica showed maximum MAI values in comparison to other plant species situated at residential site. Additionally, monitoring of particulate matter (PM10) observed to highest at highway, followed by mining, residential, and control sites. Overall A. indica representing highest APTI and effective dust capturing capacity at all sites could serve as potential pollution sinks. V. nilotica, with its very low APTI, can be marked as biomonitoring tool for detecting dust pollution.


Subject(s)
Air Pollutants , Dust , Environmental Monitoring , Mining , Plants , India , Dust/analysis , Environmental Monitoring/methods , Air Pollutants/analysis , Plants/drug effects , Air Pollution , Particulate Matter/analysis
5.
ACS Photonics ; 11(4): 1584-1591, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38645997

ABSTRACT

On-chip manipulation of photon emission from quantum emitters (QEs) is crucial for quantum nanophotonics and advanced optical applications. At the same time, the general design strategy is still elusive, especially for fully exploring the degrees of freedom of multiple channels. Here, the vectorial scattering holography (VSH) approach developed recently for flexibly designing QE-coupled metasurfaces is extended to tempering the strength of QE emission into a particular channel. The VSH power is demonstrated by designing, fabricating, and optically characterizing on-chip QE sources emitted into six differently oriented propagation channels, each representing the entangled state of orthogonal circular polarizations with different topological charges and characterized with a specific relative strength. We postulate that the demonstration of tempered multichannel photon emission from QE-coupled metasurfaces significantly broadens the possibilities provided by the holographic metasurface platform, especially those relevant for high-dimensional quantum information processing.

6.
J Water Health ; 22(4): 639-651, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38678419

ABSTRACT

Stream flow forecasting is a crucial aspect of hydrology and water resource management. This study explores stream flow forecasting using two distinct models: the Soil and Water Assessment Tool (SWAT) and a hybrid M5P model tree. The research specifically targets the daily stream flow predictions at the MH Halli gauge stations, located along the Hemvati River in Karnataka, India. A 14-year dataset spanning from 2003 to 2017 is divided into two subsets for model calibration and validation. The SWAT model's performance is evaluated by comparing its predictions to observed stream flow data. Residual time series values resulting from this comparison are then resolved using the M5P model tree. The findings reveal that the hybrid M5P tree model surpasses the SWAT model in terms of various evaluation metrics, including root-mean-square error, coefficient of determination (R2), Nash-Sutcliffe efficiency, and degree of agreement (d) for the MH Halli stations. In conclusion, this study shows the effectiveness of the hybrid M5P tree model in stream flow forecasting. The research contributes valuable insights into improved water resource management and underscores the importance of selecting appropriate models based on their performance and suitability for specific hydrological forecasting tasks.


Subject(s)
Models, Theoretical , Rain , India , Rivers , Water Movements , Hydrology , Environmental Monitoring/methods , Forecasting
7.
Chembiochem ; : e202400148, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38629812

ABSTRACT

Native chemical ligation is a key reaction in the toolbox of chemical methods for the synthesis of native and modified proteins. The catalysis of ligation is commonly performed by using small aryl-thiol molecules added at high concentrations. In this work, we incorporated thiotyrosine, a non-canonical amino acid containing an aryl-thiol moiety, into a designed cyclic protein « sans queue ni tête ¼. Importantly, the protein environment reduced the pKa of the thiol group to 5.8-5.9, which is significantly lower than the previously reported value for thiotyrosine in a short peptide (pKa 6.4). Furthermore, we demonstrated the catalytic activity of this protein both as hydrolase and in native chemical ligation of peptides. These results will be useful for the development of efficient protein catalysts (enzymes) for protein synthesis and modification.

8.
bioRxiv ; 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38405903

ABSTRACT

RNA processing mechanisms, such as alternative splicing and RNA editing, have been recognized as critical means to expand the transcriptome. Chimeric RNAs formed by intergenic splicing provide another potential layer of RNA diversification. By analyzing a large set of RNA-Seq data and validating results in over 1,200 blood samples, we identified UBA1-CDK16 , a female-specific chimeric transcript. Intriguingly, both parental genes, are expressed in males and females. Mechanistically, UBA1-CDK16 is produced by cis-splicing between the two adjacent X-linked genes, originating from the inactive X chromosome. A female-specific chromatin loop, formed between the junction sites, facilitates the alternative splicing of its readthrough precursor. This unique chimeric transcript exhibits evolutionary conservation, evolving to be female-specific from non-human primates to humans. Furthermore, our investigation reveals that UBA1-CDK16 is enriched in the myeloid lineage and plays a regulatory role in myeloid differentiation. Notably, female COVID-19 patients who tested negative for this chimeric transcript displayed higher counts of neutrophils, highlighting its potential role in disease pathogenesis. These findings support the notion that chimeric RNAs represent a new repertoire of transcripts that can be regulated independently from the parental genes, and a new class of RNA variance with potential implications in sexual dimorphism and immune responses.

9.
bioRxiv ; 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38405833

ABSTRACT

The intricate molecular environment of the native membrane profoundly influences every aspect of membrane protein (MP) biology. Despite this, the most prevalent method of studying MPs uses detergent-like molecules that disrupt and remove this vital local membrane context. This severely impedes our ability to quantitatively decipher the local molecular context and comprehend its regulatory role in the structure, function, and biogenesis of MPs. Using a library of membrane-active polymers we have developed a platform for the high-throughput analysis of the membrane proteome. The platform enables near-complete spatially resolved extraction of target MPs directly from their endogenous membranes into native nanodiscs that maintain the local membrane context. We accompany this advancement with an open-access quantitative database that provides the most efficient extraction conditions of 2065 unique mammalian MPs. Our method enables rapid and near-complete extraction and purification of target MPs directly from their endogenous organellar membranes at physiological expression levels while maintaining the nanoscale local membrane environment. Going beyond the plasma membrane proteome, our platform enables extraction from any target organellar membrane including the endoplasmic reticulum, mitochondria, lysosome, Golgi, and even transient organelles such as the autophagosome. To further validate this platform we took several independent MPs and demonstrated how our resource can enable rapid extraction and purification of target MPs from different organellar membranes with high efficiency and purity. Further, taking two synaptic vesicle MPs, we show how the database can be extended to capture multiprotein complexes between overexpressed MPs. We expect these publicly available resources to empower researchers across disciplines to capture membrane 'nano-scoops' containing a target MP efficiently and interface with structural, functional, and other bioanalytical approaches. We demonstrate an example of this by combining our extraction platform with single-molecule TIRF imaging to demonstrate how it can enable rapid determination of homo-oligomeric states of target MPs in native cell membranes.

10.
Cureus ; 16(1): e51499, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38304653

ABSTRACT

BACKGROUND: C-reactive protein (CRP) is a routine inflammation biomarker. Increased CRP levels are correlated with COVID-19. We found a marked reduction in CRP concentration on corticosteroid therapy, which in turn led to reduced mortality and duration of hospital stay. METHODS: In this retrospective cohort study, CRP levels were measured on admission and at 72 hours and compared between two groups of patients, with and without corticosteroid therapy. The study sample consisted of 105 RT-PCR-confirmed patients admitted to the ICU of the COVID ward. Out of the total patients, 57 received one or more doses of dexamethasone in addition to usual treatment, and 48 were given only usual care. RESULT: CRP at the time of admission was comparable for both groups. Also, a significant decrease in the CRP was noted in both groups 72 hours post-admission. Moreover, the decline was more marked in the steroid-administered group (CRP-baseline: 34.3mg/dL (+/-8.44), CRP at 72 hours 18.5mg/dL(+/-7.95) (p <0.00) compared to non-steroid group (CRP_baseline: 34.04mg/dL (+/-10.06), CRP at 72. Those with comorbidities were administered steroids (n=38, 66.7%) compared to those who were not (n=08, 16.7%). The average duration of hospital stay was less (5 to 7 days) in the corticosteroid-administered group compared to the other group (7 to 10 days). CONCLUSION: Routine CRP tests can predict the outcome and treatment of severe coronavirus disease. Corticosteroid treatment in COVID-19 patients is associated with reduced CRP levels within 72 hours after therapy.

11.
Cureus ; 16(1): e51726, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38318585

ABSTRACT

Background Tuberculosis (TB) and intestinal helminth infections often coexist, posing a significant health challenge. TB, caused by Mycobacterium tuberculosis, and helminths elicit distinct immune responses - Th1 for TB and Th2 for helminths. Co-infection introduces a complex immunological challenge, potentially compromising TB control. This study addresses the research gap by comparing cytokine profiles and monocyte responses in TB patients, helminth-infected individuals, and those with both. Insights gained may enhance diagnosis, treatment, and disease control strategies where TB and helminths prevail. Methods A cross-sectional observational study conducted at Indira Gandhi Institute of Medical Sciences, Patna, Bihar, aimed to compare cytokine profiles and monocyte responses in TB patients and those coinfected with TB and helminths. The study included 150 newly diagnosed active TB individuals aged 18 to 65 years. TB diagnosis was confirmed through clinical assessment, sputum microscopy, and GeneXpert (Cepheid, Sunnyvale, CA, USA) testing. Stool examination employed various methods, including the Kato-Katz technique and formalin-ether concentration. Blood samples were collected for hematological analysis, cytokine profiling, and monocyte isolation. Statistical analysis, using SPSS version 20.0 (IBM Corp., Armonk, NY, USA), included descriptive statistics, and t-test analyses. Results In our study of 150 participants, half (50.0%) showed positive helminth status. The sociodemographic analysis revealed no significant differences in age, gender, education, occupation, marital status, smoking, alcohol, BMI, diabetes, and hypertension between TB patients (n=75) and TB+Helminth patients (n=75), ensuring baseline matching. The prevalence of specific helminth infections in TB+Helminth patients included Ascaris lumbricoides (24.0%), Trichuris trichiura (18.7%), and others. Hematological parameters showed significant differences, with TB+Helminth patients exhibiting higher RBC count, hemoglobin, hematocrit, neutrophil count, and monocyte count; also eosinophil count was more raised in TB+Helminth patients (0.36 x 103/µL) when compared to TB patients (0.25 x 103/µL). Cytokine profiles and monocyte responses varied significantly between the groups, with TB patients having higher IL-4, IL-6, IFN-γ, TNF-α, and IL-1ß levels, while TB+Helminth patients had elevated IL-10. Monocyte response time did not differ significantly. Conclusion The observed differences in hematological parameters and cytokine profiles emphasize the need for tailored approaches to diagnosis and treatment in co-infected individuals. These findings suggest that the management of TB patients should consider the potential influence of helminth co-infections.

12.
Sci Rep ; 14(1): 260, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38168575

ABSTRACT

Sleep latency, the amount of time that it takes an individual to fall asleep, is a key indicator of sleep need. Sleep latency varies considerably both among and within species and is heritable, but lacks a comprehensive description of its underlying genetic network. Here we conduct a genome-wide association study of sleep latency. Using previously collected sleep and activity data on a wild-derived population of flies, we calculate sleep latency, confirming significant, heritable genetic variation for this complex trait. We identify 520 polymorphisms in 248 genes contributing to variability in sleep latency. Tests of mutations in 23 candidate genes and additional putative pan-neuronal knockdown of 9 of them implicated CG44153, Piezo, Proc-R and Rbp6 in sleep latency. Two large-effect mutations in the genes Proc-R and Piezo were further confirmed via genetic rescue. This work greatly enhances our understanding of the genetic factors that influence variation in sleep latency.


Subject(s)
Drosophila Proteins , Drosophila , Animals , Drosophila/genetics , Drosophila Proteins/genetics , Gene Regulatory Networks , Genome-Wide Association Study , Ion Channels/genetics , Polymorphism, Genetic , Sleep/genetics , Sleep Latency
13.
Nat Nanotechnol ; 19(1): 85-94, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38012273

ABSTRACT

The oligomeric organization of membrane proteins in native cell membranes is a critical regulator of their function. High-resolution quantitative measurements of oligomeric assemblies and how they change under different conditions are indispensable to understanding membrane protein biology. We report Native-nanoBleach, a total internal reflection fluorescence microscopy-based single-molecule photobleaching step analysis technique to determine the oligomeric distribution of membrane proteins directly from native membranes at an effective spatial resolution of ~10 nm. We achieved this by capturing target membrane proteins in native nanodiscs with their proximal native membrane environment using amphipathic copolymers. We applied Native-nanoBleach to quantify the oligomerization status of structurally and functionally diverse membrane proteins, including a receptor tyrosine kinase (TrkA) and a small GTPase (KRas) under growth-factor binding and oncogenic mutations, respectively. Our data suggest that Native-nanoBleach provides a sensitive, single-molecule platform to quantify membrane protein oligomeric distributions in native membranes under physiologically and clinically relevant conditions.


Subject(s)
Membrane Proteins , Membrane Proteins/chemistry , Cell Membrane/metabolism
14.
Adv Mater ; 36(4): e2304495, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37543837

ABSTRACT

Ultracompact chip-integrated single-photon sources of collimated beams with polarization-encoded states are crucial for integrated quantum technologies. However, most of currently available single-photon sources rely on external bulky optical components to shape the polarization and phase front of emitted photon beams. Efficient integration of quantum emitters with beam shaping and polarization encoding functionalities remains so far elusive. Here, ultracompact single-photon sources of linearly polarized vortex beams based on chip-integrated quantum emitter-coupled metasurfaces are presented, which are meticulously designed by fully exploiting the potential of nanobrick-arrayed metasurfaces. The authors first demonstrate on-chip single-photon generation of high-purity linearly polarized vortex beams with prescribed topological charges of 0, - 1, and +1. The multiplexing of single-photon emission channels with orthogonal linear polarizations carrying different topological charges are further realized and their entanglement is demonstarated. The work illustrates the potential and feasibility of ultracompact quantum emitter-coupled metasurfaces as a new quantum optics platform for realizing chip-integrated high-dimensional single-photon sources.

15.
MethodsX ; 12: 102494, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38089152

ABSTRACT

Ribosomal RNA (rRNA) gives rise to non-random small RNA fragments known as ribosomal-derived small RNAs (rsRNAs), which despite their biological importance, have been relatively understudied in comparison to other short non-coding RNAs. There exists a compelling necessity to develop a methodology for the identification, categorization, and quantification of rsRNAs from small RNA sequencing (sRNA-seq) data sets, considering the unique characteristics of ribosomal RNA (rRNA). To bridge this gap, we introduce 'rsRNAfinder' a specialized pipeline designed within the Snakemake framework. This analytical approach enables robust identification of rsRNAs using sRNA-seq datasets from Arabidopsis thaliana. Our methodology constitutes an integrated bioinformatic pipeline designed for different kinds of analysis.1.sRNA-seq data analysis: It performs in-depth analysis of reference-aligned sRNA-seq data, facilitating rsRNA annotation and quantification.2.Parametric reporting: Our pipeline provides comprehensive reports encompassing key parameters such as rsRNA size distributions, strandedness, genomic origin, and source rRNA origin.3.Illustrative validation: We have demonstrated the utility of our approach by conducting comprehensive rsRNA annotation in Arabidopsis thaliana. This validation reveals unique rsRNAs originating from all rRNA types, each of them distinguished by distinct identity, abundance, and length.

16.
Planta ; 259(2): 30, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38150044

ABSTRACT

MAIN CONCLUSION: The use of silver nanoparticles as elicitors in cell cultures of Rauwolfia serpentina resulted in increased levels of ajmalicine, upregulated structural and regulatory genes, elevated MDA content, and reduced activity of antioxidant enzymes. These findings hold potential for developing a cost-effective method for commercial ajmalicine production. Plants possess an intrinsic ability to detect various stress signals, prompting the activation of defense mechanisms through the reprogramming of metabolites to counter adverse conditions. The current study aims to propose an optimized bioprocess for enhancing the content of ajmalicine in Rauwolfia serpentina callus through elicitation with phytosynthesized silver nanoparticles. Initially, callus lines exhibiting elevated ajmalicine content were established. Following this, a protocol for the phytosynthesis of silver nanoparticles using seed extract from Rauwolfia serpentina was successfully standardized. The physicochemical attributes of the silver nanoparticles were identified, including their spherical shape, size ranging from 6.7 to 28.8 nm in diameter, and the presence of reducing-capping groups such as amino, carbonyl, and amide. Further, the findings indicated that the presence of 2.5 mg L-1 phytosynthesized silver nanoparticles in the culture medium increased the ajmalicine content. Concurrently, structural genes (TDC, SLS, STR, SGD, G10H) and regulatory gene (ORCA3) associated with the ajmalicine biosynthetic pathway were observed to be upregulated. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were observed. A notable increase in MDA content and a decrease in the activities of antioxidant enzymes were also observed. Our results strongly recommend the augmentation of ajmalicine content in the callus culture of R. serpentina through supplementation with silver nanoparticles, a potential avenue for developing a cost-effective process for the commercial production of ajmalicine.


Subject(s)
Antineoplastic Agents , Metal Nanoparticles , Secologanin Tryptamine Alkaloids , Silver , Terpenes , Antioxidants , Indole Alkaloids , Plant Extracts
17.
Basic Res Cardiol ; 118(1): 46, 2023 11 03.
Article in English | MEDLINE | ID: mdl-37923788

ABSTRACT

Regulation of RNA stability and translation by RNA-binding proteins (RBPs) is a crucial process altering gene expression. Musashi family of RBPs comprising Msi1 and Msi2 is known to control RNA stability and translation. However, despite the presence of MSI2 in the heart, its function remains largely unknown. Here, we aim to explore the cardiac functions of MSI2. We confirmed the presence of MSI2 in the adult mouse, rat heart, and neonatal rat cardiomyocytes. Furthermore, Msi2 was significantly enriched in the heart cardiomyocyte fraction. Next, using RNA-seq data and isoform-specific PCR primers, we identified Msi2 isoforms 1, 4, and 5, and two novel putative isoforms labeled as Msi2 6 and 7 to be expressed in the heart. Overexpression of Msi2 isoforms led to cardiac hypertrophy in cultured cardiomyocytes. Additionally, Msi2 exhibited a significant increase in a pressure-overload model of cardiac hypertrophy. We selected isoforms 4 and 7 to validate the hypertrophic effects due to their unique alternative splicing patterns. AAV9-mediated overexpression of Msi2 isoforms 4 and 7 in murine hearts led to cardiac hypertrophy, dilation, heart failure, and eventually early death, confirming a pathological function for Msi2. Using global proteomics, gene ontology, transmission electron microscopy, seahorse, and transmembrane potential measurement assays, increased MSI2 was found to cause mitochondrial dysfunction in the heart. Mechanistically, we identified Cluh and Smyd1 as direct downstream targets of Msi2. Overexpression of Cluh and Smyd1 inhibited Msi2-induced cardiac malfunction and mitochondrial dysfunction. Collectively, we show that Msi2 induces hypertrophy, mitochondrial dysfunction, and heart failure.


Subject(s)
Heart Failure , Animals , Mice , Rats , Cardiomegaly , DNA-Binding Proteins/metabolism , Heart Failure/metabolism , Mitochondria/metabolism , Muscle Proteins/genetics , Myocytes, Cardiac/metabolism , Protein Isoforms/metabolism , Protein Isoforms/pharmacology , RNA, Messenger/metabolism , RNA, Messenger/pharmacology , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Transcription Factors/metabolism , Transcription Factors/pharmacology
18.
J Oral Maxillofac Pathol ; 27(3): 607, 2023.
Article in English | MEDLINE | ID: mdl-38033961

ABSTRACT

Sarcoidosis is a rare type of multi-organ granulomatous disease. It is characterised by non-caseating necrotising granulomatous inflammation. The exact mechanism causing the disease is unknown due to its variation of manifestation in patients. The clinical presentation of this disease is protean, and often, patients remain asymptomatic throughout life. The most commonly affected organ by sarcoidosis is the lung accounting for up to 90% of all cases. Oral manifestation is a relatively rare presentation of sarcoidosis, and there are only a few cases reported till date. In this case report, the authors present a case of oral sarcoidosis of the retromolar trigone region.

19.
ACS Nano ; 17(20): 20308-20314, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37791727

ABSTRACT

Multichannel quantum emission is in high demand for advanced quantum photonic applications such as quantum communications, quantum computing, and quantum cryptography. However, to date, the most common way for shaping photon emission from quantum emitters (QEs) is to utilize free-standing (external) bulky optical components. Here, we develop the multichannel holography approach for flexibly designing on-chip QE-coupled metasurfaces that make use of nonradiatively QE-excited surface plasmon polaritons for generating far-field quantum emission, which propagates in designed directions carrying specific spin and orbital angular momenta (SAM and OAM, respectively). We further design, fabricate, and characterize on-chip quantum light sources of multichannel quantum emission encoded with different SAMs and OAMs. The holography-based inverse design approach developed and demonstrated on-chip quantum light sources with multiple degrees of freedoms, thereby enabling a powerful platform for quantum nanophotonics, especially relevant for advanced quantum photonic applications, e.g., high-dimensional quantum information processing.

20.
Adv Sci (Weinh) ; 10(33): e2303619, 2023 11.
Article in English | MEDLINE | ID: mdl-37802976

ABSTRACT

Extracellular vesicles (EVs) have emerged as a promising source of biomarkers for disease diagnosis. However, current diagnostic methods for EVs present formidable challenges, given the low expression levels of biomarkers carried by EV samples, as well as their complex physical and biological properties. Herein, a highly sensitive double digital assay is developed that allows for the absolute quantification of individual molecules from a single EV. Because the relative abundance of proteins is low for a single EV, tyramide signal amplification (TSA) is integrated to increase the fluorescent signal readout for evaluation. With the integrative microfluidic technology, the technology's ability to compartmentalize single EVs is successfully demonstrated, proving the technology's digital partitioning capacity. Then the device is applied to detect single PD-L1 proteins from single EVs derived from a melanoma cell line and it is discovered that there are ≈2.7 molecules expressed per EV, demonstrating the applicability of the system for profiling important prognostic and diagnostic cancer biomarkers for therapy response, metastatic status, and tumor progression. The ability to accurately quantify protein molecules of rare abundance from individual EVs will shed light on the understanding of EV heterogeneity and discovery of EV subtypes as new biomarkers.


Subject(s)
Biomarkers, Tumor , Extracellular Vesicles , Cell Line, Tumor , Biomarkers, Tumor/metabolism , Proteins/metabolism , Microfluidics , Extracellular Vesicles/metabolism
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