Neutralizing antibodies to interferon alfa arising during peginterferon therapy of chronic hepatitis B in children and adults: Results from the HBRN Trials.

BACKGROUND AIMS: Pegylated interferon-α (PegIFNα) is of limited utility during immunotolerant or immune active phases of chronic hepatitis B infection but is being explored as part of new cure regimens. Low/absent levels of IFNα found in some patients receiving treatment are associated with limited/no virological responses. The study aimed to determine if sera from participants inhibit IFNα activity and/or contain therapy-induced anti-IFNα antibodies. APPROACH RESULTS: Pre-treatment, on-treatment, and post-treatment sera from 61 immunotolerant trial participants on PegIFNα/entecavir therapy and 88 immune active trial participants on PegIFNα/tenofovir therapy were screened for anti-IFNα antibodies by indirect ELISA. The neutralization capacity of antibodies was measured by preincubation of sera±recombinant human IFNα added to Huh7 cells with the measurement of interferon-stimulated gene (ISG)-induction by qPCR. Correlations between serum-induced ISG inhibition, presence, and titer of anti-IFNα antibodies and virological responses were evaluated. Preincubation of on-treatment serum from 26 immunotolerant (43%) and 13 immune active (15%) participants with recombinant-human IFNα markedly blunted ISG-induction in Huh7 cells. The degree of ISG inhibition correlated with IFNα antibody titer ( p < 0.0001; r = 0.87). On-treatment development of anti-IFNα neutralizing antibodies (nAbs) was associated with reduced quantitative HBsAg and qHBeAg declines ( p < 0.05) and inhibited IFNα bioactivity to 240 weeks after PegIFNα cessation. Children developed anti-IFNα nAbs more frequently than adults ( p = 0.004) but nAbs in children had less impact on virological responses. CONCLUSIONS: The development of anti-IFNα nAbs during PegIFNα treatment diminishes responses to antiviral therapy. Understanding how and why anti-IFNα antibodies develop may allow for the optimization of IFN-based therapy, which is critical given its renewed use in HBV-cure strategies.

Identification of novel homozygous variants in FOXE3 and AP4M1 underlying congenital syndromic anophthalmia and microphthalmia.

BACKGROUND: Anophthalmia and microphthalmia are severe developmental ocular disorders that affect the size of the ocular globe and can be unilateral or bilateral. The disease is found in syndromic as well as non-syndromic forms. It is genetically caused by chromosomal aberrations, copy number variations and single gene mutations, along with non-genetic factors such as viral infections, deficiency of vitamin A and an exposure to alcohol or drugs during pregnancy. To date, more than 30 genes having different modes of inheritance patterns are identified as causing anophthalmia and microphthalmia. METHODS: In the present study, a clinical and genetic analysis was performed of six patients with anophthalmia and microphthalmia and/or additional phenotypes of intellectual disability, developmental delay and cerebral palsy from a large consanguineous Pakistani family. Whole exome sequencing followed by data analysis for variants prioritization and validation through Sanger sequencing was performed to identify the disease causing variant(s). American College of Medical Genetics and Genomics (ACMG) guidelines were applied to classify clinical interpretation of the prioritized variants. RESULTS: Clinical investigations revealed that the affected individuals are afflicted with anophthalmia. Three of the patients showed additional phenotype of intellectual disability, developmental delays and other neurological symptoms. Whole exome sequencing of the DNA samples of the affected members in the family identified a novel homozygous stop gain mutation (NM_012186: c.106G>T: p.Glu36*) in Forkhead Box E3 (FOXE3) gene shared by all affected individuals. Moreover, patients segregating additional phenotypes of spastic paraplegia, intellectual disability, hearing loss and microcephaly showed an additional homozygous sequence variant (NM_004722: c.953G>A: p.Arg318Gln) in AP4M1. Sanger sequencing validated the correct segregation of the identified variants in the affected family. ACMG guidelines predicted the variants to be pathogenic. CONCLUSIONS: We have investigated first case of syndromic anophthalmia caused by variants in the FOXE3 and AP4M1. The present findings are helpful for understanding pathological role of the mutations of the genes in syndromic forms of anophthalmia. Furthermore, the study signifies searching for the identification of second variant in families with patients exhibiting variable phenotypes. In addition, the findings will help clinical geneticists, genetic counselors and the affected family with respect to prenatal testing, family planning and genetic counseling.

Assessment of growth, and ion uptake of plant species, Conocarpus erectus and Dodonaea viscosa, on industrial solid waste.

Present study assessed the growth of two plant species and ion uptake by them grown on different proportion of industrial solid waste and garden soil. The industrial waste having high concentration of chemicals were used with garden soil at different proportion i.e. 0% (T0), 5% (T1), 10% (T2), 15% (T3) and 20% (T4). Two species namely Conocarpus erectus (alien plant) and Dodonaea viscosa (indigenous) were used as test plants in pot study. Different parameters including growth, physiology, and anatomy of plants and concentration of cations (Na+, K+, Ca2+, and Mg2+) in the plant shoot and root were measured at different time duration (initial, 1st, 2nd, 3rd and 4th month). The key objective of the study was to use these plants to establish their plantations on the barren lands where industrial solid wastes were being disposed of. C. erectus showed better growth than D. viscosa, as well as more uptake of ions. A significant increase in plant growth was observed in fourth month in T1, where plant height reached 24.5% and 46% for C. erectus and D. viscosa, respectively. At harvest, in C. erectus, no significant difference in the fresh (65-78 g) and dry weight (24-30 g) of the shoot was observed across treatments compared to the control. In D. viscosa, at the time of harvest, the fresh and dry weights of the root and shoot showed a strong, significantly decreasing pattern across T1, T2, and T3, leading to the death of the plant at T3 and T4. Further, optimum ratio of waste soil to garden soil was found as 10:90 and 20:80 to establish the plantations of D. viscosa and C. erectus, respectively in areas where such solid waste from industries are disposed. Findings can be used for the restoration of such solid waste for the sustainable management of industrial areas and their associated ecosystems.

Genomic insights into local adaptation of upland cotton in China and Pakistan.

KEY MESSAGE: Different kinship and resistance to cotton leaf curl disease (CLCuD) and heat were found between upland cotton cultivars from China and Pakistan. 175 SNPs and 82 InDels loci related to yield, fiber quality, CLCuD, and heat resistance were identified. Elite alleles found in Pakistani accessions aided local adaptation to climatic condition of two countries. Adaptation of upland cotton (Gossypium hirsutum) beyond its center of origin is expected to be driven by tailoring of the genome and genes to enhance yield and quality in new ecological niches. Here, resequencing of 456 upland cotton accessions revealed two distinct kinships according to the associated country. Fiber quality and lint percentage were consistent across kinships, but resistance to cotton leaf curl disease (CLCuD) and heat was distinctly exhibited by accessions from Pakistan, illustrating highly local adaption. A total of 175 SNP and 82 InDel loci related to yield, fiber quality, CLCuD and heat resistance were identified; among them, only two overlapped between Pakistani and Chinese accessions underscoring the divergent domestication and improvement targets in each country. Loci associated with resistance alleles to leaf curl disease and high temperature were largely found in Pakistani accessions to counter these stresses prevalent in Pakistan. These results revealed that breeding activities led to the accumulation of unique alleles and helped upland cotton become adapted to the respective climatic conditions, which will contribute to elucidating the genetic mechanisms that underlie resilience traits and help develop climate-resilient cotton cultivars for use worldwide.

Structural Diversity of 2D Molecular Self-Assemblies Arising from Carboxyl Groups Attached to a Molecule: An STM Study at the Liquid-Solid Interface.

Understanding the molecular self-assembly behavior, especially at the microscopic level, sheds light on the rational design of artificial supramolecular systems at surfaces. In this work, scanning tunneling microscopy (STM) and force field simulations were utilized to explore two molecular systems where two and four carboxyl groups are symmetrically modified onto a skeleton. The two target molecules are 4,4'-(ethyne-1,2-diyl) dibenzoic acid (EBA) and 1,1'-ethynebenzene-3,3',5,5,'-tetracarboxylic acid (TCA). The former molecular assembly led to robust close packing, whereas the latter resulted in low-density arrangements that present significant adaption, namely, undergoing phase transformations upon external stimulations, e.g., sensitive to STM-polarity switching and guest molecule incorporations.

IgA potentiates NETosis in response to viral infection.

IgA is the second most abundant antibody present in circulation and is enriched at mucosal surfaces. As such, IgA plays a key role in protection against a variety of mucosal pathogens including viruses. In addition to neutralizing viruses directly, IgA can also stimulate Fc-dependent effector functions via engagement of Fc alpha receptors (Fc-αRI) expressed on the surface of certain immune effector cells. Neutrophils are the most abundant leukocyte, express Fc-αRI, and are often the first to respond to sites of injury and infection. Here, we describe a function for IgA-virus immune complexes (ICs) during viral infections. We show that IgA-virus ICs potentiate NETosis-the programmed cell-death pathway through which neutrophils release neutrophil extracellular traps (NETs). Mechanistically, IgA-virus ICs potentiated a suicidal NETosis pathway via engagement of Fc-αRI on neutrophils through a toll-like receptor-independent, NADPH oxidase complex-dependent pathway. NETs also were capable of trapping and inactivating viruses, consistent with an antiviral function.

Development of palliative care clinical practice guidelines and referral care pathways for primary care practitioners in Pakistan.

BACKGROUND: Despite a large burden of life-limitingillness, there exists a dearth of services of palliative care in Pakistan. International guidelines have questionable applicability in Pakistan due to the socioeconomic differences. We generated a protocol describing the process of developing comprehensive palliative care guidelines and palliative care referral pathways for primary care practitioners to adopt in Pakistan. METHODS: A GRADE-ADOLOPMENT approach with modification has been employed to create guidelines for a Pakistani context. The "National Comprehensive Cancer Network Guidelines Insights: Palliative Care, Version 2.2021" was used as the source guideline. Recommendations from the source guideline were reviewed by two local palliative care specialists to either "Adopt," "Adapt" or "Exclude". The finalized recommendations were incorporated into the local palliative care guideline. Clinical diagnosis and referral pathways were made from the finalized guideline. Any gaps in management found in the pathways were filled by taking existing recommendations from other credible guidelines. RESULTS: Twenty-seven recommendations were adopted without modification. No recommendations were deemed to be adapted and 15 were excluded. The referral care pathways created were reflective of the local guideline and included elements of initial assessment, preliminary management, reassessment, and referral. 6 additional recommendations were made. CONCLUSION: The described clinical practice guidelines and primary care clinical referral pathways will aid to standardize palliative care provision in Pakistan. These can be used by other resource constrained settings to develop guidelines within their own local context.

Efficient chromium removal from leather industrial wastewater in batch experimental study: Green synthesis and characterization of zinc oxide nanoparticles using Ficus benghalensis extracts.

The urgent need to address the severe environmental risk posed by chromium-contaminated industrial wastewater necessitates the development of eco-friendly cleanup methodologies. Utilizing the Ficus benghalensis plant extracts, the present study aims to develop green zinc oxide nanoparticles for the removal of Cr metal ions from wastewater. The leaves of Ficus benghalensis, often known as the banyan tree, were used to extract a solution for synthesizing ZnO NPs. These nanoparticles were developed with the goal of efficiently eliminating chromium (Cr) from industrial effluents. Batch studies were carried out to assess the efficiency of these synthesized ZnO NPs in treating leather industrial effluent, with aiming for optimal chromium removal. This involved measuring the nanoparticles' capacity to adsorb Cr ions from wastewater samples by comparing chromium levels before and after treatment. Removal efficiency for Cr was estimated through the batches such as optimization of pH, contact time, initial Cr concentration and sorbent dose of ZnO NPs were of the batches. These synthesized ZnO NPs were found to be successful in lowering chromium levels in wastewater to meet permissible limit. The nanoparticles exhibited their highest absorption capacity, reaching 94 % (46 mg/g) at pH 4, with a contact time of 7 hours with the optimum sorbent dose of 0.6 g/L. Hence, the excellent adsorption capabilities of these nanoparticles, together with their environmentally benign manufacturing technique, provide a long-term and efficient solution for chromium-contaminated wastewater treatment. Its novel nature has the potential to significantly improve the safety and cleanliness of water ecosystems, protecting the both i.e. human health and the environment.

DFT, Molecular Docking, ADME, and Cardiotoxicity studies of Persuasive Thiazoles as Potential Inhibitors of the Main Protease of SARS-CoV-2.

This study explores the capability of thiazoles as potent inhibitors of SARS-CoV-2 Mpro. Seventeen thiazoles (1-17) were screened for their linking affinity with the active site of SARS-CoV-2 Mpro and compared with the FDA-recommended antiviral drugs, Remdesivir and Baricitinib. Density Functional Theory (DFT) calculations provided electronic and energetic properties of these ligands, shedding light on their stability and reactivity. Molecular docking analysis revealed that thiazole derivatives exhibited favorable linking affinities with various functional sites of SARS-CoV-2 proteins, including spike receptor-linking zone, nucleocapsid protein N-terminal RNA linking zone, and Mpro. Notably, compounds 3, 10, and 12 displayed the best interaction with 6LZG as compared to FDA-approved antiviral drugs Remdesivir and Baricitinib, while compounds 1, 10, and 8 exhibited strong linking with 6M3M and also better than Remdesivir and Baricitinib. Additionally, compounds 3, 1, and 6 showed promising interactions with 6LU7 but only compound 3 performed better than Baricitinib. An ADME (Absorption, Distribution, Metabolism, and Excretion) study provided insights into the pharmacokinetics and drug-likeness of these compounds, with all ligands demonstrating good physicochemical characteristics, lipophilicity, water solubility, pharmacokinetics, drug-likeness, and medicinal chemistry attributes. The results suggest that these selected thiazole derivatives hold promise as potential candidates for further drug development.

LAMP3/CD63 Expression in Early and Late Endosomes in Human Vaginal Epithelial Cells Is Associated with Enhancement of HSV-2 Infection.

Herpes simplex virus 2 (HSV-2) is a lifelong sexually transmitted virus that disproportionately infects women through heterosexual transmission in the vaginal tract. The vaginal epithelium is known to be highly susceptible to HSV-2 infection; however, the cellular mechanism of HSV-2 uptake and replication in vaginal epithelium has not been extensively studied. Previously, we observed that lysosomal-associated membrane protein-3 (LAMP3/CD63) was among the highly upregulated genes during HSV-2 infection of human vaginal epithelial cell line VK2, leading us to posit that LAMP3/CD63 may play a role in HSV-2 infection. Consequently, we generated two gene-altered VK2-derived cell lines, a LAMP3-overexpressed (OE) line and a LAMP3 knockout (KO) line. The wild-type VK2 and the LAMP3 OE and KO cell lines were grown in air-liquid interface (ALI) cultures for 7 days and infected with HSV-2. Twenty-four hours postinfection, LAMP3 OE cells produced and released significantly higher numbers of HSV-2 virions than wild-type VK2 cells, while virus production was greatly attenuated in LAMP3 KO cells, indicating a functional association between LAMP3/CD63 expression and HSV-2 replication. Fluorescence microscopy of HSV-2-infected cells revealed that HSV-2 colocalized with LAMP3 in both early endosomes and lysosomal compartments. In addition, blocking endosomal maturation or late endosomal/lysosomal fusion using specific inhibitors resulted in reduced HSV-2 replication in VK2 cells. Similarly, LAMP3 KO cells exhibited very low viral entry and association with endosomes, while LAMP3 OE cells demonstrated large amounts of virus that colocalized with LAMP3/CD63 in endosomes and lysosomes. IMPORTANCE Collectively, these results showed that HSV-2 is taken up by human vaginal epithelial cells through an endosomal-lysosomal pathway in association with LAMP3, which plays a crucial role in the enhancement of HSV-2 replication. These findings provide the basis for the future design of antiviral agents for prophylactic measures against HSV-2 infection.

Gastrointestinal bleeding in recipients of left ventricular assist devices-a systematic review.

The twenty-first century has revolutionized the management of congestive heart failure with the widespread use of left ventricular assist devices and other treatment modalities that improve morbidity and mortality after the failure of medical management. These novel devices come with significant side effects. One of the most common side effects of left ventricular assist devices is the increased frequency of lower gastrointestinal bleeding compared to heart failure patients without left ventricular assist devices. Multiple etiologies of recurrent gastrointestinal bleeding in such patients have been studied. The decreased amount of von Willebrand factor polymers is now recognized as one of the most common causes of increased incidence of gastrointestinal bleeding in patients with left ventricular assist devices alongside increased arteriovenous malformations. Multiple treatment modalities have been identified to prevent and treat gastrointestinal bleeding in these patients. Since the use of left ventricular assist devices is becoming more prevalent in patients with advanced heart failure, we decided to conduct this systematic review. The article summarizes the incidence, pathophysiology, and management of lower gastrointestinal bleeding in patients with left ventricular assist devices.

Effect of titanium dioxide nanoparticles and co-composted biochar on growth and Cd uptake by wheat plants: A field study.

Cadmium (Cd) is a common toxic trace element found in agricultural soils which is mainly due to anthropogenic activities. Cadmium posed a significant risk to humans all around the world due to its cancer-causing ability. The current study demonstrated the effects of soil-applied biochar (BC) and foliar-applied titanium dioxide nanoparticles (TiO2 NPs) (at a rate of 0.5% and 75 mg/L respectively) alone or in combination on growth and Cd accumulation in wheat plants under field experiment. Soil applied BC and foliar TiO2 NPs, as well as BC coupled with TiO2 NPs, reduced Cd contents in grains by 32%, 47%, and 79%, than control respectively. The usage of NPs and BC boosted the plant height as well as chlorophyll contents by lowering oxidative injury and changing selected antioxidant enzyme activities in leaves than control plants. The combined use of NPs and BC prevented excess Cd accumulation in grains over the critical level (0.2 mg/kg) for cereals. The health risk index (HRI) due to Cd was reduced by 79% by co-composted BC + TiO2 NPs treatment than control. Although, HRI was lower than one for all treatments but this may exceed the limit if grains obtained from such field consumed over long periods. In conclusion, TiO2 NPs and BC amendments can be implemented in fields across the globe where excess Cd is present in soils. Additional studies on the use of such approaches in more precise experimental settings are needed in order to address this environmental problem at larger scale.

Synthesis, characterization and antifungal potential of titanium dioxide nanoparticles against fungal disease (Ustilago tritici) of wheat (Triticum aestivum L.).

Nanoparticles (NPs) preparation using a green as well as environmentally acceptable processes has achieved a lot of attention in recent decade. The current study compared the synthesis of titania (TiO2) nanoparticles synthesized from leaf extracts of two plant species (Trianthema portulacastrum, Chenopodium quinoa) and traditional approach by chemical preparation. The effects of no calcination on the physical characteristics of TiO2 NPs as well as their antifungal effects were examined and compared with the already reported calcinated TiO2 NPs. The produced TiO2 NPs were evaluated using high-tech techniques such as X-ray diffraction (XRD), scanning electron microscope, energy dispersive spectroscopy (EDX), and elemental mapping. TiO2 NPs prepared by sol-gel technique (T1) and prepared from extractions from leaves of T. portulacastrum (T2), and C. quinoa (T3) were either calcinated or non calcinated and tested against fungal disease (Ustilago tritici) of wheat for antifungal efficacy. The -peak (2θ) at 25.3 was confirmed by XRD to be connected with the anatase (101) form in both cases but before calcination, NPs were lacking the rutile and brookite peaks. The results showed that all types of TiO2 NPs examined had good antifungal activity against U. tritici, but those made from C. quinoa plant extract have good antifungal activity against disease. TiO2 NPs which are produced by the green methods (T2, T3) have the highest antifungal activity (58%, 57% respectively), while minimal activity (19%) was recorded when NPs were synthesized using the sol-gel method (T1) with 25 µl/mL. Non calcinated TiO2 NPs have less antifungal potential than calcined TiO2 NPs. It can be concluded that calcination may be preferred for efficient antifungal activity when using titania nanoparticles. The green technology may be used on a larger scale with less damaging TiO2 NP production and can be utilized against fungal disease on wheat crop to reduce crop losses worldwide.

Impact of an outpatient palliative care consultation and symptom clusters in terminal patients at a tertiary care center in Pakistan.

BACKGROUND: Patients with terminal diseases may benefit physically and psychosocially from an outpatient palliative care visit. Palliative care services are limited in Pakistan. An improved understanding of the symptom clusters present in our population is needed. The first outpatient palliative care center in Karachi, Pakistan, was established at our tertiary care institution. The primary aim of this study was to evaluate the impact of a palliative care outpatient consultation on symptom burden in patients with a terminal diagnosis. The secondary aim was to analyze the symptom clusters present in our population. METHODS: Patients with a terminal diagnosis referred to our outpatient palliative department between August 2020-August 2022 were enrolled. The Edmonton Symptom Assessment Scale (ESAS) questionnaire was administered at the initial visit and the first follow-up visit at one month. Change in symptom burden was assessed using a Wilcoxon signed ranks test. A principal component analysis with varimax rotation was performed on the symptoms reported at the initial visit to evaluate symptom clusters. The palliative performance scale (PPS) was used to measure the performance status of palliative care patients. RESULTS: Among the 78 patients included in this study, the average age was 59 ± 16.6 years, 52.6% were males, 99% patients had an oncological diagnosis, and the median duration between two visits was 14 (Q1-Q3: (7.0, 21.0) days. The median PPS level was 60% (Q1-Q3: 50-70). Overall, ESAS scores decreased between the two visits (6.0 (2.8, 11.0), p < 0.001) with statistically significant improvement in pain (5.0 vs. 2.5, p < 0.001), loss of appetite (5.0 vs. 4.0, p = 0.004), depression (2.0 vs. 0.0, p < 0.001), and anxiety (1.5 vs. 0.0, p = 0.032). Based on symptoms at the initial visit, 3 clusters were present in our population. Cluster 1 included anxiety, depression, and wellbeing; cluster 2 included nausea, loss of appetite, tiredness, and shortness of breath; and cluster 3 included drowsiness. CONCLUSION: An outpatient palliative care visit significantly improved symptom burden in patients with a terminal diagnosis. Patients may benefit from further development of outpatient palliative care facilities to improve the quality of life in terminally ill patients.

Enhancing chromium removal and recovery from industrial wastewater using sustainable and efficient nanomaterial: A review.

Water contamination can be detrimental to the human health due to higher concentration of carcinogenic heavy metals such as chromium (Cr) in the wastewater. Many traditional methods are being employed in wastewater treatment plants for Cr removal to control the environmental impacts. Such methods include ion exchange, coagulation, membrane filtration, and chemical precipitation and microbial degradation. Recent advances in materials science and green chemistry have led to the development of nanomaterial that possess high specific surface areas and multiple functions, making them suitable for removing metals such as Cr from wastewater. Literature shows that the most efficient, effective, clean, and long-lasting approach for removing heavy metals from wastewater involves adsorbing heavy metals onto the surface of nanomaterial. This review assesses the removal methods of Cr from wastewater, advantages and disadvantages of using nanomaterial to remove Cr from wastewater and potential negative impacts on human health. The latest trends and developments in Cr removal strategies using nanomaterial adsorption are also explored in the present review.

Effect of green-synthesized copper oxide nanoparticles on growth, physiology, nutrient uptake, and cadmium accumulation in Triticum aestivum (L.).

Cadmium (Cd) stress in crops has been serious concern while little is known about the copper oxide nanoparticles (CuO NPs) effects on Cd accumulation by crops. This study investigated the effectiveness of CuO NPs in mitigating Cd contamination in wheat (Triticum aestivum L.) cultivation through a pot experiment, presenting an eco-friendly solution to a critical agricultural concern. The CuO NPs, synthesized using green methods, exhibited a circular shape with a crystalline structure and a particle size ranging from 8 to 12 nm. The foliar spray of CuO NPs was applied in four different concentrations i.e. control, 25, 50, 75, 100 mg/L. The obtained data demonstrated that, in comparison to the control group, CuO NPs had a beneficial influence on various growth metrics and straw and grain yields of T. aestivum. The green CuO NPs improved T. aestivum growth and physiology under Cd stress, enhanced selected enzyme activities, reduced oxidative stress, and decreased malondialdehyde levels in the T. aestivum plants. CuO NPs lowered Cd contents in T. aestivum tissues and boosted the uptake of essential nutrients from the soil. Overall, foliar applied CuO NPs were effective in minimizing Cd contents in grains thereby reducing the health risks associated with Cd excess in humans. However, more in depth studies with several plant species and application methods of CuO NPs are required for better utilization of NPs in agricultural purposes.

MIA-NDN: Microservice-Centric Interest Aggregation in Named Data Networking.

The named data networking (NDN)-based microservice-centric in-network computation poses various challenges in terms of interest aggregation and pending interest table (PIT) lifetime management. A same-named microservice-centric interest packet may have a different number of input parameters with nonidentical input values. In addition, the same-named interest packet with the same number of parameters may have different corresponding parameter values. The vanilla NDN request aggregation (based on the interest name, while ignoring the input parameters count and/or their corresponding values) may result in false aggregation. Moreover, the microservice-centric requested computations may fail to accomplish in the default 4s PIT timer due to the input size. To address these challenges, this paper presents MIA-NDN: microservice-centric interest aggregation in named data networking. We designed microservice-centric interest-naming to enable name-based communication. MIA-NDN develops a robust interest aggregation mechanism that not only performs the interest aggregation based on the interest name but also considers the input parameter counts and their corresponding values in the interest aggregation process to avoid false packet aggregations. A dynamic PIT timer mechanism based on input size was devised that avoids the PIT entry losses if the execution time exceeds the default PIT timer value to avoid computation losses and uphold the application quality of service (QoS). Extensive software-based simulations confirm that the MIA-NDN outperforms the benchmark scheme in terms of microservice-centric interest aggregation, microservice satisfaction rate, and communication overhead.

Rhein Induces Oral Cancer Cell Apoptosis and ROS via Suppresse AKT/mTOR Signaling Pathway In Vitro and In Vivo.

Oral cancer remains the leading cause of death worldwide. Rhein is a natural compound extracted from the traditional Chinese herbal medicine rhubarb, which has demonstrated therapeutic effects in various cancers. However, the specific effects of rhein on oral cancer are still unclear. This study aimed to investigate the potential anticancer activity and underlying mechanisms of rhein in oral cancer cells. The antigrowth effect of rhein in oral cancer cells was estimated by cell proliferation, soft agar colony formation, migration, and invasion assay. The cell cycle and apoptosis were detected by flow cytometry. The underlying mechanism of rhein in oral cancer cells was explored by immunoblotting. The in vivo anticancer effect was evaluated by oral cancer xenografts. Rhein significantly inhibited oral cancer cell growth by inducing apoptosis and S-phase cell cycle arrest. Rhein inhibited oral cancer cell migration and invasion through the regulation of epithelial-mesenchymal transition-related proteins. Rhein induced reactive oxygen species (ROS) accumulation in oral cancer cells to inhibit the AKT/mTOR signaling pathway. Rhein exerted anticancer activity in vitro and in vivo by inducing oral cancer cell apoptosis and ROS via the AKT/mTOR signaling pathway in oral cancer. Rhein is a potential therapeutic drug for oral cancer treatment.

Effects of soil amendments on soil acidity and crop yields in acidic soils: A world-wide meta-analysis.

Soil amendments, including lime, biochar, industrial by-products, manure, and straw are used to alleviate soil acidification and improve crop productivity. Quantitative insight in the effect of these amendments on soil pH is limited, hampering their appropriate use. Until now, there is no comprehensive evaluation of the effects of soil amendments on soil acidity and yield, accounting for differences in soil properties. We synthesized 832 observations from 142 papers to explore the impact of these amendments on crop yield, soil pH and soil properties, focusing on acidic soils with a pH value below 6.5. Application of lime, biochar, by-products, manure, straw and combinations of them significantly increased soil pH by 15%, 12%, 15%, 13%, 5% and 17%, and increased crop yield by 29%, 57%, 50%, 55%, 9%, and 52%, respectively. The increase of soil pH was positively correlated with the increase in crop yield, but the relationship varied among crop types. The most substantial increases in soil pH and yield in response to soil amendments were found under long-term applications (>6 year) in strongly acidic (pH < 5.0) sandy soils with a low cation exchange capacity (CEC, <100 mmolc kg-1) and low soil organic matter content (SOM, <12 g kg-1). Most amendments increased soil CEC, SOM and base saturation (BS) and decreased soil bulk density (BD), but lime application increased soil BD (1%) induced by soil compaction. Soil pH and yield were positively correlated with CEC, SOM and BS, while yield declined when soils became compacted. Considering the impact of the amendments on soil pH, soil properties and crop yield as well as their costs, the addition of lime, manure and straw seem most appropriate in acidic soils with an initial pH range from <5.0, 5.0-6.0 and 6.0-6.5, respectively.

Fertilization as the most critical factor affecting yield response and agronomic efficiency of phosphorus in Chinese rice production: evidence from multi-location field trials.

BACKGROUND: Efficient utilization of phosphorus (P) has been a major challenge for sustainable agriculture. However, the responses of fertilizer rate, region, soil properties, cropping systems and genotypes to P have not been investigated comprehensively and systematically. RESULTS: A comprehensive analysis of 9863 fertilizer-P experiments on rice cultivation in China showed that rice yield  increased first and then fell down with the addition of P fertilizer, and the highest yield of 7963 kg ha-1 was observed under 100% P treatment. Under 100% P treatment, the yield response of applied P (YRP ) and agronomic efficiency of applied P (AEP ) were 12.8% and 30.1 kg ha-1 , respectively. Lower soil pH (< 5.5) and organic matter (< 30.0 g kg-1 ) were associated with lower YRP and AEP . By contrast, soil available P < 25.0 mg kg-1 resulted in decreased YRP (15.3 to 11.4%) and AEP (32.3 kg kg-1 to 26.2 kg kg-1 ), whereas soil available P > 25.0 mg kg-1 maintained the relatively stable YRP and AEP . Also, the YRP and AEP were significantly higher for single-cropping rice compared to other cropping systems. Moreover, the rice genotypes such as 'Longdun', 'Kendao' and 'Jigeng' had higher YRP and AEP than the average value. Overall, the fertilizer-P rate was the primary factor affecting YRP and AEP , and the recommended P fertilizer rate can be reduced by 9-21 kg P ha-1 compared to existing expert recommendations. CONCLUSION: The present study highlights the role of fertilizer-P rate in maximizing the YRP and AEP , thereby providing a strong basis for future fertilizer management in rice cultivation systems. © 2023 Society of Chemical Industry.