Hypobaric hypoxia modulated structural characteristics of circulating cell-free DNA in high-altitude pulmonary edema.

The utility of cell-free (cf) DNA has extended as a surrogate or clinical biomarker for various diseases. However, a more profound and expanded understanding of the diverse cfDNA population and its correlation with physiological phenotypes and environmental factors is imperative for using its full potential. The high-altitude (HA; altitude > 2,500 m above sea level) environment characterized by hypobaric hypoxia offers an observational case-control design to study the differential cfDNA profile in patients with high-altitude pulmonary edema (HAPE) (number of subjects, n = 112) and healthy HA sojourners (n = 111). The present study investigated cfDNA characteristics such as concentration, fragment length size, degree of integrity, and subfractions reflecting mitochondrial-cfDNA copies in the two groups. The total cfDNA level was significantly higher in patients with HAPE, and the level increased with increasing HAPE severity (P = 0.0036). A lower degree of cfDNA integrity of 0.346 in patients with HAPE (P = 0.001) indicated the prevalence of shorter cfDNA fragments in circulation in patients compared with the healthy HA sojourners. A significant correlation of cfDNA characteristics with the peripheral oxygen saturation levels in the patient group demonstrated the translational relevance of cfDNA molecules. The correlation was further supported by multivariate logistic regression and receiver operating characteristic curve. To our knowledge, our study is the first to highlight the association of higher cfDNA concentration, a lower degree of cfDNA integrity, and increased mitochondrial-derived cfDNA population with HAPE disease severity. Further deep profiling of cfDNA fragments, which preserves cell-type specific genetic and epigenetic features, can provide dynamic physiological responses to hypoxia.NEW & NOTEWORTHY This study observed altered cell-free (cf) DNA fragment patterns in patients with high-altitude pulmonary edema and the significant correlation of these patterns with peripheral oxygen saturation levels. This suggests deep profiling of cfDNA fragments in the future may identify genetic and epigenetic mechanisms underlying physiological and pathophysiological responses to hypoxia.

Microbial nanotechnology for agriculture, food, and environmental sustainability: Current status and future perspective.

The field of nanotechnology has the mysterious capacity to reform every subject it touches. Nanotechnology advancements have already altered a variety of scientific and industrial fields. Nanoparticles (NPs) with sizes ranging from 1 to 100 nm (nm) are of great scientific and commercial interest. Their functions and characteristics differ significantly from those of bulk metal. Commercial quantities of NPs are synthesized using chemical or physical methods. The use of the physical and chemical approaches remained popular for many years; however, the recognition of their hazardous effects on human well-being and conditions influenced serious world perspectives for the researchers. There is a growing need in this field for simple, non-toxic, clean, and environmentally safe nanoparticle production methods to reduce environmental impact and waste and increase energy productivity. Microbial nanotechnology is relatively a new field. Using various microorganisms, a wide range of nanoparticles with well-defined chemical composition, morphology, and size have been synthesized, and their applications in a wide range of cutting-edge technological areas have been investigated. Green synthesis of the nanoparticles is cost-efficient and requires low maintenance. The present review highlights the synthesis of the nanoparticles by different microbes, their characterization, and their biotechnological potential. It further deals with the applications in biomedical, food, and textile industries as well as its role in biosensing, waste recycling, and biofuel production.

Trends in Hybrid Cultured Meat Manufacturing Technology to Improve Sensory Characteristics.

The projected growth of global meat production over the next decade is attributed to rising income levels and population expansion. One potentially more pragmatic approach to mitigating the adverse externalities associated with meat production involves implementing alterations to the production process, such as transitioning to cultured meat, hybrid cultured meat, and meat alternatives. Cultured meat (CM) is derived from animal stem cells and undergoes a growth and division process that closely resembles the natural in vivo cellular development. CM is emerging as a widely embraced substitute for traditional protein sources, with the potential to alleviate the future strain on animal-derived meat production. To date, the primary emphasis of cultured meat research and production has predominantly been around the ecological advantages and ethical considerations pertaining to animal welfare. However, there exists substantial study potential in exploring consumer preferences with respect to the texture, color, cuts, and sustainable methodologies associated with cultured meat. The potential augmentation of cultured meat's acceptance could be facilitated through the advancement of a wider range of cuts to mimic real muscle fibers. This review examines the prospective commercial trends of hybrid cultured meat. Subsequently, the present state of research pertaining to the advancement of scaffolding, coloration, and muscle fiber development in hybrid cultured meat, encompassing plant-based alternatives designed to emulate authentic meat, has been deliberated. However, this discussion highlights the obstacles that have arisen in current procedures and proposes future research directions for the development of sustainable cultured meat and meat alternatives, such as plant-based meat production.

Association of transient mitochondrial functional impairment with acute heat exposure in children from Muzaffarpur region of Bihar, India.

Over the past several years, the Muzaffarpur district of Bihar (India) has witnessed recurrent outbreaks of acute encephalitis illness of unknown etiology, called acute encephalitis syndrome (AES) among young children, especially during the peak-summer season. Pesticide exposure, viral encephalitis, and litchi toxin intake have all been postulated as potential sources of the ailment. However, no conclusive etiology for AES has been identified in the affected children. During recent rounds of the outbreak, metabolic abnormalities have been documented in these children, and a direct correlation was observed between higher environmental temperature during the peak-summer month and AES caseload. The clinical and metabolic profiles of these children suggested the possible involvement of mitochondrial dysfunction during heat stress as one of the several contributory factors leading to multisystem metabolic derangement. The present study observed that mitochondrial function parameters such as cell death, mitochondrial membrane potential, oxidative stress, and mitochondrial pathway-related gene expression in peripheral blood mononuclear cells (PBMCs) isolated from children were affected in peak-summer when compared to post-summer months. Similar observations of mitochondrial function parameters along with impaired bioenergetic parameters were demonstrated in the heat-exposed model of PBMCs isolated from healthy adult individuals. In conclusion, the results suggested that there is an association of transient mitochondrial dysfunction when exposed to sustained heat during the summer months. One may consider mitochondrial dysfunction as one of the important factors leading to an outbreak of AES among the children from affected regions though this needs to be substantiated with further studies.

Taurine deficiency as a driver of aging.

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.

A Review on Saliva-Based Health Diagnostics: Biomarker Selection and Future Directions.

The human body has a unique way of saying when something is wrong with it. The molecules in the body fluids can be helpful in the early detection of diseases by enabling health and preventing disease progression. These biomarkers enabling better healthcare are becoming an extensive area of research interest. Biosensors that detect these biomarkers are becoming the future, especially Point Of Care (POC) biosensors that remove the need to be physically present in the hospital. Detection of complex and systemic diseases using biosensors has a long way to go. Saliva-based biosensors are gaining attention among body fluids due to their non-invasive collection and ability to detect periodontal disease and identify systemic diseases. The possibility of saliva-based diagnostic biosensors has gained much publicity, with companies sending home kits for ancestry prediction. Saliva-based testing for covid 19 has revealed effective clinical use and relevance of the economic collection. Based on universal biomarkers, the detection of systemic diseases is a booming research arena. Lots of research on saliva-based biosensors is available, but it still poses challenges and limitations as POC devices. This review paper talks about the relevance of saliva and its usefulness as a biosensor. Also, it has recommendations that need to be considered to enable it as a possible diagnostic tool.

Acute fatty liver of pregnancy complicated by coagulopathy: A case report.

Key Clinical Message: We present the case of a rare obstetric emergency, which is usually fatal. Our case highlights suspicion of AFLP in patients presenting with jaundice in the third trimester with good maternal and fetal outcomes after a timely intervention. Abstract: Acute fatty liver of pregnancy (AFLP) is a rare, obstetric emergency characterized by maternal liver dysfunction that can lead to maternal and fetal complications. We report a case of 28-year-old primigravida 39 weeks gestation diagnosed with AFLP complicated by coagulopathy with good maternal and fetal outcomes after a timely intervention.

Circulating free DNA integrity index and promoter methylation of tumor suppressor gene P16, DAPK and RASSF1A as a biomarker for oropharyngeal squamous cell carcinoma.

Circulating free DNA (cfDNA) is in use for the non-invasive diagnosis of tumors. Methylation of tumor suppressor genes (TSGs) is an early event in carcinogenesis and may serve as tumor biomarker. We have investigated cfDNA integrity and methylation of tumor suppressor genes P16, DAPK and RASSF1A in serum cfDNA of oropharyngeal squamous cell carcinoma (OPSCC) comparing paired serum and tumor tissue samples to evaluate their diagnostic use. Prospective case-control study, paired serum and tissue samples from 56 OPSCC, and 15 normal controls (NC). Sybr green Quantitate real time PCR was used for cfDNA quantification through amplification ALU 115 and 247 fragments. Promoter methylation of was analyzed in paired samples using methylation specific PCR. There was significantly high cfDNA integrity in OPSCC compared to normal control (p = < 0.0001). The cfDNA integrity values were significantly higher and associated with nodal status (p = 0.016). The AUC for cfDNA integrity was 0.967. The P16, DAPK and RASSF1 promoters were significantly hypermethylated in serum of OPSCC compared to NC with high concordance in tissue (up to 96.55 %). The gene promoter methylation of P16 was associated with smoking (p = 0.030), RASSF1A with stage (p = 0.011). The combination of ALU115 with cfDNA integrity and combination of gene methylation increases diagnostic sensitivity. In followup samples the cfDNA change was not different. Liquid biopsy approach including cfDNA integrity, methylation profiling in cfDNA, in combination or separately can assist in the diagnosis of OPSCC along with radio diagnostic scan. Serum changes represent changes in tissue with very high concordance.

Magnetically recoverable sol-gel auto-combustion developed Ni1-xCuxDyyFe2-yO4 magnetic nanoparticles for photocatalytic, electrocatalytic, and antibacterial applications.

Copper and dysprosium doped NiFe2O4 magnetic nanomaterials, Ni1-xCuxDyyFe2-yO4 (x = y = 0.00, 0.01, 0.02, 0.03), was prepared by utilizing sol-gel auto-combustion approach to inspect the photodegradation of methylene blue (MB) pollutant and also, to perform the electrocatalytic water splitting and antibacterial studies. The XRD analysis reveal the growth of a single-phase spinel cubic structure for produced nanomaterials. The magnetic traits show an increasing trend in saturation magnetization (Ms) from 40.71 to 47.90 emu/g along with a decreasing behaviour of coercivity from 158.09 to 156.34 Oe at lower and higher Cu and Dy doping content (x = 0.0-0.01). The study of optical band gap values of copper and dysprosium-doped nickel nanomaterials decreased from 1.71 to 1.52 eV. This will increase the photocatalytic degradation of methylene blue pollutant from 88.57% to 93.67% under natural sunlight, respectively. These findings clearly show that under natural sunlight irradiation for 60 min, the produced N4 photocatalyst displays the greatest photocatalytic activity with a maximum removal percentage of 93.67%. The electrocatalytic characteristics of produced magnetic nanomaterials for both HER and OER were examined with a Calomel electrode taking as a reference in a 0.5 N H2SO4 and 0.1 N KOH electrolyte. The N4 electrode demonstrated considerable 10 and 0.024 mA/cm2 of current density, with onset potentials of 0.99 and 1.5 V for HER and OER and also, have tafel slopes of 58.04 and 295 mV/dec, respectively. The antibacterial activity for produced magnetic nanomaterials was examined against various bacteria (Bacillus subtilis, Staphylococcus aureus, S. typhi, and P. aeruginosa) in which N3 sample produced significant inhibition zone against gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) but no zone of inhibition against gram-negative bacteria (S. typhi and P. aeruginosa). With all these superior traits, the produced magnetic nanomaterials are highly valuable for the wastewater remediation, hydrogen evolution, and biological applications.

Immunophenotypic characterization of normal and abnormal plasma cells in bone marrow of newly diagnosed multiple myeloma patients.

Background: Identification of plasma cells into abnormal (APC) and normal (NPC) compartments is of utmost importance in flow cytometric (FC) analysis of multiple myeloma (MM) and related plasma cell dyscrasias for diagnosis, prognosis, and follow-up. No single phenotypic marker is sufficient to distinguish NPC from APC. Materials and Methods: 43 newly diagnosed cases of MM and 13 controls were included in the study. Bone marrow (BM) samples from the 2nd pass were processed on the same day with antibodies against CD38, CD138, CD19, CD81, CD45, CD117, CD200, CD56, cytoKappa, and cytoLambda in a 4-color experiment with CD38 and CD138 as gating antibodies. Results: Mean APC% in cases was 96.5%. The expected Immunophenotype (IP) of APC which is CD19-/56+/45-/81-/117+/200+ was found in only 13/43 MM cases. In 30/43 cases, APC revealed deviation from expected IP either for single or a combination of markers. Sensitivity for APC detection was highest for CD19 (95.2%) followed by CD56 (90.4%) and CD81 (83.7%). Specificity was highest for CD19 (100%), CD56 (100%), and CD81 (100%) followed by CD117 (92.3%). Combination of markers with maximum sensitivity to detect APC (97.6%) was CD81- or CD19- and CD200+ or CD56+ (two markers); and for NPC (92.3%) was CD81+ and CD19+ and CD56- (three markers). Conclusion: Plasma cell IP can be highly variable with multiple minor subpopulations in both cases and normal controls. CD 19 and CD56 are highly informative markers for a 4-color experiment. Assessment of multiple markers in an 8-10 color experiment is more informative but the lack of advanced flow cytometers should not limit the use of FC in a 4-color approach. Our results emphasize that even basic equipment with limited fluorochrome can provide meaningful information if used appropriately.

Pheochromocytoma disguised as gestational hypertensive disease during pregnancy: A case report.

Pheochromocytoma is often diagnosed prior to pregnancy. Sometimes, the disease may be diagnosed for the first-time during pregnancy masking itself as a hypertensive disease in pregnancy. Early diagnosis and timely, appropriate management reduce possible maternal and fetal complications. We identified a case of pheochromocytoma during pregnancy misdiagnosed as preeclampsia.

Regioselective C(sp2)-H imidation of arenes by redox neutral visible-light photocatalysis.

We report herein a redox neutral visible light-induced regioselective C(sp2)-H imidation of electron-rich arenes and heteroarenes using conceptually designed redox-active 1 as a source of the N-centered imidyl radical. Structurally diverse aromatic imides were obtained in moderate to good yields. This methodology has been successfully employed for the late stage imidation of complex molecules and has also been applied towards the formal total synthesis of the marine natural products carpatamides A, B and D. It has further been shown that the generated imides can easily be converted to the corresponding anilines in situ directly.

Identification of probable inhibitors for the DNA polymerase of the Monkeypox virus through the virtual screening approach.

Given the paucity of antiviral treatments for monkeypox disease, caused by the Monkeypox virus (MPXV), there is a pressing need for the development/identification of new drugs to treat the infection. MPXV possesses a linear dsDNA genome that is replicated by a DNA replication complex of which DNA polymerase (DPol) forms an important component. Owing to the importance of DPol in the viral life cycle, identifying/designing small molecules abolishing its function could yield new antivirals. In this study, we first used the AlphaFold artificial intelligence program to model the 3D structure of the MPXV DPol; like the fold of DPol from other organisms, the MPXV DPol structure has the characteristic exonuclease, thumb, palm, and fingers sub-domains arrangement. Subsequently, we have identified several inhibitors through virtual screening of ZINC and antiviral libraries. Molecules with phenyl scaffold along with alanine-based and tetrazole-based molecules showed the best docking score of -8 to -10 kcal/mol. These molecules bind in the palm and fingers sub-domains interface region, which partially overlaps with the DNA binding path. The delineation of DPol/inhibitor interactions showed that majorly active site residues ASP549, ASP753, TYR550, ASN551, SER552, and ASN665 interact with the inhibitors. These compounds exhibit good Absorption, Distribution, Metabolism and Excretion properties.

Sensory Evaluation of Plant-Based Meat: Bridging the Gap with Animal Meat, Challenges and Future Prospects.

Globally, the demand for plant-based meat is increasing rapidly as these products are becoming quite popular among vegans and vegetarians. However, its development is still in the early stage and faces various technological challenges; the imitation of the sensory profile of meat is the most challenging part as these products are meant to be an alternative to animal meat. The development of a product similar to meat requires accurate selection of ingredients and processing techniques. An understanding of the relevant sensory profile can help in constructing products and technologies that are consumer-centric and sustainable. In this review, we focus on the comparative differences in the sensory profiles of animal meat and plant-based meat alternatives, particularly regarding the color, texture, and flavor, along with the methods used to compare them. This paper also explains the sensory evaluation and how it affects consumer preference and acceptability. Additionally, a direction for further research on developing better plant-based meat products is suggested.

Respiratory tract infection: an unfamiliar risk factor in high-altitude pulmonary edema.

The dramatic changes in physiology at high altitude (HA) as a result of the characteristic hypobaric hypoxia condition can modify innate and adaptive defense mechanisms of the body. As a consequence, few sojourners visiting HA with mild or asymptomatic infection may have an enhanced susceptibility to high-altitude pulmonary edema (HAPE), an acute but severe altitude sickness. It develops upon rapid ascent to altitudes above 2500 m, in otherwise healthy individuals. Though HAPE has been studied extensively, an elaborate exploration of the HA disease burden and the potential risk factors associated with its manifestation are poorly described. The present review discusses respiratory tract infection (RTI) as an unfamiliar but important risk factor in enhancing HAPE susceptibility in sojourners for two primary reasons. First, the symptoms of RTI s resemble those of HAPE. Secondly, the imbalanced pathways contributing to vascular dysfunction in HAPE also participate in the pathogenesis of the infectious processes. These pathways have a crucial role in shaping host response against viral and bacterial infections and may further worsen the clinical outcomes at HA. Respiratory tract pathogenic agents, if screened in HAPE patients, can help in ascertaining their role in disease risk and also point toward their association with the disease severity. The microbial screenings and identifications of pathogens with diseases are the foundation for describing potential molecular mechanisms underlying host response to the microbial challenge. The prior knowledge of such infections may predict the manifestation of disease etiology and provide better therapeutic options.

Clinicopathological Challenges in Tumors of the Nasal Cavity and Paranasal Sinuses: Our Experience.

Background and objective Nasal and paranasal lesions are one of the most common otorhinolaryngological presentations encountered in clinical practice. Common presenting symptoms of these lesion range from nasal blockades, facial swellings, pain, nasal discharge, and epistaxis to orbital and ear symptoms. Diagnosis can be tricky as these symptoms are common in inflammatory conditions and tumors. The aim of our study was to observe the epidemiology and clinical pathological findings in patients with nasal and paranasal masses presenting to our institute and discuss the challenges in proper diagnosis and management due to similar presentations, and the role of histopathological examination (HPE) and immunohistochemistry (IHC) in overcoming these challenges. Methods The IPD records of 396 patients were taken up for the study. All the specimens were sent in 10% neutral buffered formalin for examination as biopsy for diagnosis or after surgical excision. After adequate fixation, the biopsy specimen was submitted for routine processing, followed by paraffin embedding, and stained with hematoxylin and eosin (H&E). Special stains like periodic acid-Schiff (PAS) and Ziehl-Neelsen (ZN) stains for acid-fast bacilli (AFB) were used as required. IHC was performed in the required samples. IHC markers were performed on representative paraffin-embedded sections according to the streptavidin-biotin immunoperoxidase technique as needed. The findings were noted, and histology was correlated with clinical presentations and investigations, tabulated, and statistically analyzed using SPSS Statistics (IBM, Armonk, NY). Results Of note, 67.92%% were non-neoplastic lesions whereas 18.18% came out to be benign neoplasms and 13.88% were malignant lesions on HPE. Nasal obstruction was the most common presenting symptom (73.23% of patients) followed by nasal mass (64.14% of cases). Inflammatory sinonasal polyps were the most prominent cases in our study, accounting for 41.16% of all lesions; 18.68% fungal RS (mucormycosis) were seen in our study and 4.54% were cases of juvenile nasopharyngeal angiofibroma (JNA). The majority of benign neoplasms encountered were Schneiderian papilloma or inverted papilloma (06.81%). Eighteen (4.54%) cases of squamous cell carcinomas (SCC) were seen in our study and 2.77% (n=11) cases were of adenoid cystic carcinoma. Of 18 cases of SCC, moderately differentiated SCC carcinoma accounted for 10 cases followed by poorly differentiated SCC (5/18) and nonkeratinizing SCC (3/18). IHC for p40 was performed in all the cases of nonkeratinizing SCC, which showed strong and diffuse nuclear positivity. Conclusion The nasal cavity is the site of the most varied presentation of tumors in the upper respiratory tract. Mass in the nose and paranasal sinus (PNS) form a heterogeneous group of lesions with varied histopathological features. The proximity of the area to the eyes and brain warrants early definitive diagnosis so that the lesion is treated before it can involve important and vital centers. Even though malignant nasal tumors have a very low incidence, they cause a lot of morbidity due to their long course and frequent local recurrences. Nasal tumors tend to become polypoidal. Epithelioid papilloma of the nasal cavity often resembles a nasal polyp. Clinical diagnosis can be challenging due to similar presentations and appearances, and hence histological examination is a vital tool for the timely diagnosis of such patients.

Dynamics of cell-free DNA in predicting response in adult diffuse glioma on chemoradiotherapy.

BACKGROUND: Adult diffuse glioma (ADG) is a heterogeneous primary brain tumor with a variable prognosis and treatment response. Tissue biomarkers and molecular genetic profiling form an integral part of diagnosis and prognostication. However, obtaining tissue in inoperable locations and diagnosis of recurrence can be an issue. Cell-free DNA (cfDNA) may help to meet these challenges in the management of ADG. OBJECTIVES: The study aimed to serially quantify cfDNA in ADG on chemoradiation and to correlate mutational profiling of the cfDNA with biopsy. MATERIAL AND METHODS: The study group comprised of histopathological confirmed ADG (n = 50), including grade II, III and IV glioma, and controls (n = 25). Serum cfDNA was extracted using ChargeSwitch gDNA 1 mL Serum Kit (Invitrogen, USA) and quantified using SYBR based quantitative polymerase chain reaction (qPCR). Next-generation sequencing (NGS) was performed in 07 pre-operative and 05 post-operative cfDNA and tumor biopsy DNA on an Ion personal genome machine (IonPGM) with an in-house designed NGS panel (including TP53, ATRX, and IDH1 and IDH2). RESULTS: In patients with ADG, the pre-radiotherapy cfDNA level was significantly higher (Median; 113.46 ng/mL) than normal controls (Median; 74.37 ng/mL), (p = 0.048). Non-responders had significantly higher cfDNA levels (Median; 184.4 ng/mL), than responders (Median; 68.12 ng/mL), (p = 0.023). TP53 gene mutation was most common in both pre-operative and post-operative cfDNA samples. CONCLUSION: Pre-radiotherapy cfDNA levels are associated with clinical outcomes independent of other prognostic factors. Targeted NGS in pre-operative cfDNA matches the results of IHC analysis with high concordance, and it may be helpful in inoperable cases or ADG recurrence.

Transmigration of copper IUCD leading to abdominal abscess: A case report.

Far migrated IUCD (Intrauterine Contraceptive Device) is an uncommon condition that has different manifestations depending upon its location. We present the case of a 22-year-old primipara who had a spontaneous abortion after IUCD placement and suffered chronic right lower abdominal pain thereafter. Diagnostic laparoscopy revealed Cu-IUCD in the right iliac fossa.

Papaya Leaf Curl Virus (PaLCuV) Infection on Papaya (Carica papaya L.) Plants Alters Anatomical and Physiological Properties and Reduces Bioactive Components.

Papaya leaves are used frequently for curing scores of ailments. The medicinal properties of papaya leaves are due to presence of certain bioactive/pharmacological compounds. However, the papaya leaf curl virus (PaLCuV), a geminivirus, is a major threat to papaya cultivation globally. During the present investigation, we observed that PaLCuV infection significantly altered the anatomy, physiology, and bioactive properties of papaya leaves. As compared to healthy leaves, the PaLCuV-infected leaves were found to have reduced stomatal density (76.83%), stomatal conductance (78.34%), photosynthesis rate (74.87%), water use efficiency (82.51%), chlorophyll (72.88%), carotenoid (46.63%), osmolality (48.55%), and soluble sugars (70.37%). We also found lower enzymatic activity (superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT)-56.88%, 85.27%, and 74.49%, respectively). It was found that the size of guard cells (50%), transpiration rate (45.05%), intercellular CO2 concentration (47.81%), anthocyanin (27.47%), proline content (74.17%), malondialdehyde (MDA) (106.65%), and electrolyte leakage (75.38%) was elevated in PaLCuV-infected leaves. The chlorophyll fluorescence analysis showed that the infected plant leaves had a significantly lower value of maximal quantum yield of photosystem II (PSII (Fv/Fm), photochemical quantum yield of photosystem I (PSI (Y(I)), and effective quantum yield of PSII (Y(II)). However, in non-photochemical quenching mechanisms, the proportion of energy dissipated in heat form (Y(NPQ)) was found to be significantly higher. We also tested the bioactivity of infected and healthy papaya leaf extracts on a Caenorhabditis elegans (C. elegans) model system. It was found that the crude extract of papaya leaves significantly enhanced the life span of C. elegans (29.7%) in comparison to virus-infected leaves (18.4%) on application of 100 µg/mL dose of the crude extract. Our research indicates that the PaLCuV-infected leaves not only had anatomical and physiological losses, but that pharmacological potential was also significantly decreased.

Genomic profiling of gallbladder carcinoma: Targetable mutations and pathways involved.

Gallbladder cancer (GBC) carries a poor prognosis and frequently present in late stages of disease. Identification of targetable molecular changes for selecting appropriate treatment and identifying prognostic and therapeutic subsets is required. Next-generation sequencing (NGS) using a frequently mutated for GBC may provide a reference for clinical management. The primary aim of the current study was to analyze the frequency of individual genetic alterations in GBC and to correlate with clinicopathological characteristics. A retrospective study was conducted using 22 gene panel examined NGS based approach for the detection of actionable genomic mutations in 37 GBC patients. The genetic and clinicopathological characteristics were analyzed. The number of mutations in cases was ranged from 1 to 15. A total of 171 mutations were identified in FFPE tissue DNA. The most common alterations were TP53 (90.90%), SMAD4 (60.60%), NOTCH1(45.45)& ERBB2 (45.45%), PIK3CA (33.33%) and MET (30.30)& PTEN (30.30%). Among the 22 gene panel, the TP53 gene was associated with histopathological differentiation (p = 0.0001), ERBB4 & ALK mutation was associated with necrosis (p = 0.012, 0.027), EGFR mutation was associated with mucin status (p = 0.023) and ERBB2 gene mutation was associated with T stage (p = 0.036). The study provides an overview of the genetic alterations in GBC patients.Targetable mutations are present in 89.91% cases of GBC which include SMAD4, NOTCH1, ERBB2&4, PIK3CA, MET, PTEN, EGFR, KRAS and BRAF. Metastatic disease was associated with high frequency of CTNNB1, KRAS and NRAS gene mutations.