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Summary Current treatments for postmenopausal osteoporosis suffer from side effects. Safe and natural milk proteins, ribonuclease, and lactoferrin promote formation of new capillaries and bone formation. A ribonuclease-enriched lactoferrin supplement studied here, demonstrates significant reduction in resorption and increase in formation, towards restoring the balance of bone turnover within 6 months. Introduction Osteoporosis, a major health issue among postmenopausal women, causes increased bone resorption and reduced bone formation. A reduction in angiogenesis could also contribute to this imbalance. Current treatments such as hormone replacement therapy and bisphosphonates have drawbacks of severe side effects. Milk ribonuclease (RNase) is known to promote angiogenesis and lactoferrin (LF) to stimulate bone formation by osteoblasts. We examine the effect of ribonuclease-enriched lactoferrin supplement on the bone health of postmenopausal women. Methods A total of 38 healthy, postmenopausal women, aged 45 to 60 years were randomized into placebo or RNAse-enriched-LF (R-ELF) supplement groups. The bone health status was monitored by assessing bone resorption markers, serum N-telopeptides (NTx), and urine deoxypyridinoline (Dpd) crosslinks and serum bone formation markers, bone-specific alkaline phosphatase (BAP), and osteocalcin (OC). Results R-ELF supplementation demonstrated a decrease in urine Dpd levels by 14% (19% increase for placebo) and serum NTx maintained at 24% of the baseline (41% for placebo), while serum BAP and OC levels showed a 45% and 16% elevation (25% and 5% for placebo). Conclusions R-ELF supplementation demonstrated a statistically significant reduction in bone resorption and increase in osteoblastic bone formation, to restore the balance of bone turnover within a short period.

Unilateral left pulmonary edema due to inadvertent surgical occlusion of left superior and inferior pulmonary veins is not only an exceedingly rare complication of mitral valve surgeries but also a diagnostic challenge in the postoperative recovery unit. Described here is a case of a 38-year-old male who developed progressively worsening unilateral left pulmonary edema after mitral valve replacement on postoperative day-1. The diagnosis was mostly by the exclusion of multiple possible differentials and was confirmed during reexploration surgery.

Transition-metal-oxide based perovskites belong to the strongly correlated electron system exhibiting composition dependent metal-insulator transition. Their electronic properties can be tuned by doping them with right material by right amount for application in the diverse areas of material science. This article presents the preparation of crystalline thin films of Fe -doped LaNi 1-x Fe x O 3 ( x  = 0, 0.1, 0.2, 0.4) on glass substrate by spin-coating of chemical solutions. Annealing the films at a suitable temperature for optimum time plays a crucial role in obtaining good crystalline samples. We performed structural characterizations of the films using X-ray diffraction spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Electrical conductivity of the films was measured by four-probe technique at 30˚ C, 50˚ C, 80˚ C, and 100˚ C. We observed a non-ohmic insulating behaviour for the sample with x  = 0.4 while all the other films with lower doping level showcased linear voltage-current relationship with metallic temperature dependence. Graphical Abstract

Dengue virus serotype 2 (DENV-2) is a predominant cause of severe dengue and a key determinant of dengue-associated liver injury. This review integrates recent findings on the molecular and cellular mechanisms of DENV-2 hepatotropism, focusing on viral replication, cellular stress responses, and immune-mediated damage. The interplay between hepatocytes, Kupffer cells, and innate and adaptive immune responses, culminating in cytokine storm and immune-mediated hepatocyte apoptosis, is dissected. Integrating in vitro and in vivo findings, this review highlights how viral replication and immune dysregulation converge to cause hepatic injury. Future research should prioritize antiviral, immunomodulatory, and hepatoprotective approaches aimed at reducing the risk of dengue-associated liver failure.

Cardiovascular disease is one of the main causes of death worldwide which can be easily diagnosed by listening to the murmur sound of heartbeat sounds using a stethoscope. The murmur sound happens at the Lub-Dub, which indicates there are abnormalities in the heart. However, using the stethoscope for listening to the heartbeat sound requires a long time of training then only the physician can detect the murmuring sound. The existing studies show that young physicians face difficulties in this heart sound detection. Use of computerized methods and data analytics for detection and classification of heartbeat sounds will improve the overall quality of sound detection. Many studies have been worked on classifying the heartbeat sound; however, they lack the method with high accuracy. Therefore, this research aims to classify the heartbeat sound using a novel optimized Adaptive Neuro-Fuzzy Inferences System (ANFIS) by artificial bee colony (ABC). The data is cleaned, pre-processed, and MFCC is extracted from the heartbeat sounds. Then the proposed ABC-ANFIS is used to run the pre-processed heartbeat sound, and accuracy is calculated for the model. The results indicate that the proposed ABC-ANFIS model achieved 93% accuracy for the murmur class. The proposed ABC-ANFIS has higher accuracy in compared to ANFIS, PSO ANFIS, SVM, KSTM, KNN, and other existing studies. Thus, this study can assist physicians to classify heartbeat sounds for detecting cardiovascular disease in the early stages.

SARS‐CoV‐2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus–host protein–protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia (‘cytokine storm’), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25–70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new ‘onset’ clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.

A graft-transmissible disease displaying red veins, red blotches and total reddening of leaves in red-berried wine grape (Vitis vinifera L.) cultivars was observed in commercial vineyards. Next-generation sequencing technology was used to identify etiological agent(s) associated with this emerging disease, designated as grapevine redleaf disease (GRD). High quality RNA extracted from leaves of grape cultivars Merlot and Cabernet Franc with and without GRD symptoms was used to prepare cDNA libraries. Assembly of highly informative sequence reads generated from Illumina sequencing of cDNA libraries, followed by bioinformatic analyses of sequence contigs resulted in specific identification of taxonomically disparate viruses and viroids in samples with and without GRD symptoms. A single-stranded DNA virus, tentatively named Grapevine redleaf-associated virus (GRLaV), and Grapevine fanleaf virus were detected only in grapevines showing GRD symptoms. In contrast, Grapevine rupestris stem pitting-associated virus, Hop stunt viroid, Grapevine yellow speckle viroid 1, Citrus exocortis viroid and Citrus exocortis Yucatan viroid were present in both symptomatic and non-symptomatic grapevines. GRLaV was transmitted by the Virginia creeper leafhopper (Erythroneura ziczac Walsh) from grapevine-to-grapevine under greenhouse conditions. Molecular and phylogenetic analyses indicated that GRLaV, almost identical to recently reported Grapevine Cabernet Franc-associated virus from New York and Grapevine red blotch-associated virus from California, represents an evolutionarily distinct lineage in the family Geminiviridae with genome characteristics distinct from other leafhopper-transmitted geminiviruses. GRD significantly reduced fruit yield and affected berry quality parameters demonstrating negative impacts of the disease. Higher quantities of carbohydrates were present in symptomatic leaves suggesting their possible role in the expression of redleaf symptoms.

Background Red blotch disease, caused by Grapevine red blotch virus (GRBV, genus Grablovirus , family Geminiviridae ), negatively impacts vine health, fruit yield, and quality, leading to substantial economic losses to growers. While recent studies have enhanced our understanding of the epidemiology of GRBV and its effects, little is known about the molecular basis of the host-virus interactions. Since small RNAs (sRNAs) are known to play a central role in host-virus interactions, this study was undertaken to investigate sRNA dynamics in leaves and berries at two phenological stages (asymptomatic pre- and symptomatic post-véraison) of GRBV-infected grapevines ( Vitis vinifera cv. Merlot). Results Among the 140 microRNAs (miRNAs) detected, 41 isoforms belonging to 18 miRNA families exhibited significant differential expression in response to GRBV infection. Furthermore, 50 miRNAs showed differential expression in samples from pre- and post-véraison stages. A total of 58 conserved and 41 novel targets for known V. vinifera miRNAs were validated using degradome sequencing data from leaf samples of pre- and post-véraison stages. Additionally, virus-derived siRNAs (vsiRNAs) specific to GRBV were present only in GRBV-positive samples. The vsiRNAs predominantly ranged from 19 to 24 nucleotides (nt), with the 21nt size being the most abundant. Mapping vsiRNAs across the GRBV genome revealed an uneven distribution, with vsiRNA-generating hotspots predominantly located in the V3 ORF. Of the 83 most abundant vsiRNAs, grapevine target transcripts were identified for eight of them. Conclusions Identification of differentially expressed miRNAs and vsiRNAs, as well as their targets, offered important insights into various pathways and mechanisms that were affected in grapevine infected with GRBV and in modulating different host responses in leaves and berries. This research serves as a foundation for a better understanding of the molecular interactions in this plant-geminivirus pathosystem.

Grapevine leafroll disease (GLD) is an economically important virus disease affecting wine grapes (Vitis vinifera L.), but little is known about its effect on wine chemistry and sensory composition of wines. In this study, impacts of GLD on fruit yield, berry quality and wine chemistry and sensory features were investigated in a red wine grape cultivar planted in a commercial vineyard. Own-rooted Merlot vines showing GLD symptoms and tested positive for Grapevine leafroll-associated virus 3 and adjacent non-symptomatic vines that tested negative for the virus were compared during three consecutive seasons. Number and total weight of clusters per vine were significantly less in symptomatic relative to non-symptomatic vines. In contrast to previous studies, a time-course analysis of juice from grapes harvested at different stages of berry development from symptomatic and non-symptomatic vines indicated more prominent negative impacts of GLD on total soluble solids (TSS) and berry skin anthocyanins than in juice pH and titratable acidity. Differences in TSS between grapes of symptomatic and non-symptomatic vines were more pronounced after the onset of véraison, with significantly lower concentrations of TSS in grapes from symptomatic vines throughout berry ripening until harvest. Wines made from grapes of GLD-affected vines had significantly lower alcohol, polymeric pigments, and anthocyanins compared to corresponding wines from grapes of non-symptomatic vines. Sensory descriptive analysis of 2010 wines indicated significant differences in color, aroma and astringency between wines made from grapes harvested from GLD-affected and unaffected vines. The impacts of GLD on yield and fruit and wine quality traits were variable between the seasons, with greater impacts observed during a cooler season, suggesting the influence of host plant × environment interactions on overall impacts of the disease.