The classification of locally rotationally symmetric Bianchi type V spacetime based on its killing vector fields is presented in this paper using an algebraic method. In this approach, a Maple algorithm is employed to transform the Killing's equations into a reduced evolutive form. Subsequently, the integration of the Killing's equations is carried out subject to the constraints provided by the algorithm. The algorithm demonstrates that there exist fifteen distinct metrics that could potentially possess Killing vector fields. Upon solving the Killing equations for all fifteen metrics, it is observed that seven out of the fifteen metrics exclusively exhibit the minimum number of Killing vector fields. The remaining eight metrics admit a varying number of Killing vector fields, specifically 6, 7, or 10. The Kretschmann scalar has been computed for each of the obtained metrics, revealing that all of them possess a finite Kretschmann scalar and thus exhibit regular behavior.
Background. Autoimmune hepatitis (AIH) is increasingly seen in children worldwide and it is more severe in children compared to adults. This study highlights the biochemical and clinical aspect, treatment given and outcome of the disease including pediatric liver transplantation. Study. Retrospective review (2012-2022) was done in Shifa International Hospital, Islamabad. Patients under 18 years diagnosed with AIH were included. Data related to age, gender, clinical features, laboratory investigations including liver function test, liver biopsy findings and imaging modalities were included. Results. Fifteen patients were included 7 (47%) were males and 8 (53%) females. AIH type 1 was the most common type seen in 7 (46%), AIH type 2 in 5 (33%) and seronegative in 3 (20%). Jaundice was the most common symptom. Liver biopsy showed findings characteristic of AIH. Liver transplant performed in 3 patients. Conclusion. The study highlights the varied clinical presentation of AIH in Pakistani children.
Burn wounds are one of the most hazardous issues globally. Silkworm produces a protein called sericin. Sericin assists in wound healing by facilitating the proliferation of keratinocytes and fibroblasts while turmeric is potentially helpful in wound healing because of its antioxidant, anti-inflammatory, and anti-infectious activities. The current study aimed to investigate the synergetic and individual effects of turmeric, sericin, and their nanoparticles on burn wounds in mice. The female mice of 2 months of age (each weighing 29-30 g) were arbitrarily distributed in seven groups. Five mice were added to each group. Burn wounds were induced in mice by using a hot metal rod. Burn wounds were evaluated histologically and morphologically. Turmeric nanoparticles substantially improved the wound contraction area as compared to the negative control group and other treatment groups. The serum level of Glutathione (4.9±0.1umol/L), Catalase (6.0±0.2mmol/ml), Glutathione Peroxidase (183.4±5.1U/L), Superoxide dismutase (194.6±5.1 U/ml) were significantly increased in the turmeric nanoparticles (TNPs) group as compared to the negative control (2.8±0.1umol/L, 3.5±0.1mmol/ml, 87.8±3.0U/L, and 92.0±4.8U/ml respectively). The minimum levels of Malondialdehyde (3.8±0.2mmol/L) were noticed in TNPs group contrary to the negative control (7.4±0.2mmol/L). The restoration of the epidermis was also observed to be faster in TNPs group as compared to all other treatment groups. The histopathological analysis also demonstrated the effectiveness of turmeric, sericin, and their nanoparticles. In conclusion, turmeric, sericin, and their nanoparticles are effective in improving the healing process of burn wounds, but TNPs showed the most effective results as compared to all other treatment groups.
BACKGROUND: Hexaploid bread wheat underwent a series of polyploidization events through interspecific hybridizations that conferred adaptive plasticity and resulted in duplication and neofunctionalization of major agronomic genes. The genetic architecture of polyploid wheat not only confers adaptive plasticity but also offers huge genetic diversity. However, the contribution of different gene copies (homeologs) encoded from different subgenomes (A, B, D) at different growth stages remained unexplored. METHODS: In this study, hybrid of elite cultivars of wheat were developed via reciprocal crosses (cytoplasm swapping) and phenotypically evaluated. We assessed differential expression profiles of yield-related negative regulators in these cultivars and their F1 hybrids and identified various cis-regulatory signatures by employing bioinformatics tools. Furthermore, the preferential expression patterns of the syntenic triads encoded from A, B, and D subgenomes were assessed to decipher their functional redundancy at six different growth stages. RESULTS: Hybrid progenies showed better heterosis such as up to 17% increase in the average number of grains and up to 50% increase in average thousand grains weight as compared to mid-parents. Based on the expression profiling, our results indicated significant dynamic transcriptional expression patterns, portraying the different homeolog-dominance at the same stage in the different cultivars and their hybrids. Albeit belonging to same syntenic triads, a dynamic trend was observed in the regulatory signatures of these genes that might be influencing their expression profiles. CONCLUSION: These findings can substantially contribute and provide insights for the selective introduction of better cultivars into traditional and hybrid breeding programs which can be harnessed for the improvement of future wheat.
Plant Breeding , Triticum , Triticum/genetics , Hybridization, Genetic , Hybrid Vigor/genetics
Solid waste management is one of the biggest challenges of the current era. The combustible fractions in the waste stream turn out to be a good energy source if converted into refuse-derived fuel. Researchers worldwide are successfully converting it into fuel. However, certain challenges are associated with its application in gasifiers, boilers, etc. to co-fire it with coal. These include high moisture content, low calorific value, and difficulty to transport and store. The present study proposed torrefaction as a pretreatment of the waste by heating it in the range of 200 °C-300 °C in the absence of oxygen at atmospheric pressure. The combustible fraction from the waste stream consisting of wood, textile, paper, carton, and plastics termed as mixed waste was collected and torrefied at 225 °C, 250 °C, 275 °C, and 300 °C for 15 and 30 min each. It was observed that the mass yield and energy yield decreased to 45% and 62.96% respectively, but the energy yield tended to increase by the ratio of 1.39. Proximate analysis showed that the moisture content and volatile matter decreased for torrefied samples, whereas the ash content and fixed carbon content increased. Similarly, the elemental analysis revealed that the carbon content increased around 23% compared to raw samples with torrefaction contrary to hydrogen and oxygen, which decreased. Moreover, the higher heating value (HHV) of the torrefied samples increased around 1.3 times as compared to the raw sample. This pretreatment can serve as an effective solution to the current challenges and enhance refuse-derived fuel's fuel properties.
Rice (Oryza sativa L.) is an important member of the family Poaceae and more than half of world population depend for their dietary nutrition on rice. Rice cultivars with higher yield, resilience to stress and wider adaptability are essential to ensure production stability and food security. The fundamental objective of this study was to identify higher-yielding rice genotypes with stable performance and wider adaptability in a rice growing areas of Pakistan. A triplicate RCBD design experiment with 20 Green Super Rice (GSR) advanced lines was conducted at 12 rice growing ecologies in four Provinces of Pakistan. Grain yield stability performance was assessed by using different univariate and multivariate statistics. Analysis of variance revealed significant differences among genotypes, locations, and G x E interaction for mean squares (p < 0.05) of major yield contributing traits. All the studied traits except for number of tillers per plant revealed higher genotypic variance than environmental variance. Broad sense heritability was estimated in the range of 44.36% to 98.60%. Based on ASV, ASI, bi, Wi2, σ2i and WAAS statistics, the genotypes G1, G4, G5, G8, G11 and G12 revealed lowest values for parametric statistics and considered more stable genotypes based on paddy yield. The additive main effects and multiplicative interaction (AMMI) model revealed significant variation (p < 0.05) for genotypes, non-signification for environment and highly significant for G × E interaction. The variation proportion of PC1 and PC2 from interaction revealed 67.2% variability for paddy yield. Based on 'mean verses stability analysis of GGE biplot', 'Which-won-where' GGE Biplot, 'discriminativeness vs. representativeness' pattern of stability, 'IPCA and WAASB/GY' ratio-based stability Heat-map, and ranking of genotypes, the genotypes G1, G2, G3, G5, G8, G10, G11 and G13 were observed ideal genotypes with yield potential more than 8 tons ha-1. Discriminativeness vs. representativeness' pattern of stability identifies two environments, E5 (D.I Khan, KPK) and E6 (Usta Muhammad, Baluchistan) were best suited for evaluating genotypic yield performance. Based on these findings we have concluded that the genotypes G1, G2, G3, G5, G8, G10, G11 and G13 could be included in the commercial varietal development process and future breeding program.
Genotype , Oryza , Oryza/genetics , Oryza/growth & development , Pakistan , Phenotype , Plant Breeding/methods , Gene-Environment Interaction , Edible Grain/genetics , Edible Grain/growth & development , Quantitative Trait, Heritable
In this comprehensive investigation, a novel pH-responsive hydrogel system comprising mimosa seed mucilage (MSM), ß-cyclodextrin (ß-CD), and methacrylic acid (MAA) was developed via free radical polymerization technique to promote controlled drug delivery. The hydrogel synthesis involved strategic variations in polymer, monomer, and crosslinker content in fine-tuning its drug-release properties. The resultant hydrogel exhibited remarkable pH sensitivity, selectively liberating the model drug (Capecitabine = CAP) under basic conditions while significantly reducing release in an acidic environment. Morphological, thermal, and structural analyses proved that CAP has a porous texture, high stability, and an amorphous nature. In vitro drug release experiments showcased a sustained and controlled release profile. Optimum release (85.33 %) results were recorded over 24 h at pH 7.4 in the case of MMB9. Pharmacokinetic evaluation in healthy male rabbits confirmed bioavailability enhancement and sustained release capabilities. Furthermore, rigorous toxicity evaluations and histopathological analyses ensured the safety and biocompatibility of the hydrogel. This pH-triggered drug delivery system can be a promising carrier system for drugs involving frequent administrations.
BACKGROUND: Leukocyte parameters are predicted to be affected in patients with metabolic syndrome (MetS). We conducted a systematic review and meta-analysis to study the association between white blood cell parameters (WBC) in people with and without MetS. METHODS: PubMed, EMBASE, Scopus and Cochrane Library databases were searched according to the study protocol. The standardized mean difference (SMD) and 95% confidence intervals (CI) of leukocyte markers between individuals with and without MetS were pooled using an inverse variance model. Additionally, a subgroup analysis by sex was performed where possible. Methodological quality assessment was conducted using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane Risk of Bias tool 2.0 for Randomized Controlled Trials (RCTs). RESULTS: Of 6068 articles identified, 63 were eligible for the study. Compared to controls, individuals with MetS showed significantly higher concentrations of total leukocyte count (SMD [95% CI]: 0.60 [0.55-0.65]; Pâ <â .00001; I2â =â 100%), neutrophil counts (0.32 [0.28-0.37]; Pâ <â .00001; I2â =â 99%), lymphocyte counts (0.15 [0.07-0.23]; Pâ =â .0004; I2â =â 100%), basophil counts (0.01 [0.00-0.02]; Pâ =â .02; I2â =â 98%), monocyte counts (0.05 [0.02-0.09]; Pâ =â .003; I2â =â 99%), and neutrophil-to-lymphocyte ratio (0.24 [0.15-0.33]; Pâ <â .00001; I2â =â 98%). There were no significant differences in the eosinophil count (0.02 [-0.01 to 0.05]; Pâ =â .19; I2â =â 96%) and monocyte-to-lymphocyte ratio (0.06 [-0.05 to 0.17]; Pâ =â .27; I2â =â 100%) between patients with and without MetS, however, the lymphocyte-to-monocyte ratio (0.52 [-0.81 to -0.23]; Pâ =â .0005; I2â =â 52%) tended to be significantly lower in patients with MetS. CONCLUSION: Biomarkers such as total leukocyte count, neutrophil count, lymphocyte count, basophil count, monocyte count and neutrophil-to-lymphocyte ratio are associated with higher levels in patients in MetS and thus can potentially be used for early detection of MetS.
Metabolic Syndrome , Humans , Leukocytes/metabolism , Leukocyte Count , Neutrophils/metabolism , Lymphocytes/metabolism
The present experimental study investigates the thermal and hydraulic performance of Ethylene Glycol (EG)-based ZnO nanofluids (NFs) in circular minichannel test sections, each of 330 mm in length and 1.0-2.0 mm inner diameters. The experiments were conducted under steady-state constant heat flux and laminar flow conditions. The stable ZnO/EG-based NFs were synthesized using a standard two-step method in varying nanoparticles (NPs) loadings (0.012-0.048 wt%). The morphological characteristics, crystal structure, and specific surface area (SSA) showed that the NPs were sized in nm, possessing excellent crystal structure and enhanced surface area. Thermal conductivity (TC) and viscosity (VC) of the NFs were examined in the 20-60 °C temperature range. Both TC and VC possessed an increasing trend with the rise in concentration of the NPs. However, with the temperature rise, TC increased while the VC decreased and vice versa. The highest enhancements in TC and VC were 14.38 % and 15.22 %, respectively, at 40 °C and 0.048 wt% of NPs loading. The highest enrichment recorded in the local and average heat transfer coefficient (HTC) were 14.80 % and 13.48% in a minichannel with 1.0 mm inner diameter, respectively. It was directly proportional to the NPs loading and volume flow rate of the NFs. The friction factor was also directly proportional to the test section's inner cross-sectional area, while the pressure gradient showed an inverse behavior. An inverse relationship was recorded for the volume flow rate of the NFs and vice versa. Maximum friction factor and the pressure drop for all three minichannel test sections were recorded as 34.58 % and 32.16 %, respectively. The well-known Shah correlation predicted the local and average HTC within ±15.0 %, while the friction factor and the pressure gradient were well predicted by the Darcy correlation within the ±10.0 % range.
Geckos and their products have been used in Asian traditional medicine. Medicinal properties of desert-dwelling Gecko species, Crossobamon orientalis remain unexplored. In this study, natural bioactive macromolecules present in oil extracted from C. orientalis (COO) and their biological activities were evaluated. Chemical constitution of COO was explored by using gas chromatography mass spectrometry. Antioxidant, antiviral, and antibacterial activities of COO extracts were assessed using various assays, including DPPH free-radical-protocol, HET-CAM method, in ovo-antiviral technique, and disc-diffusion method. GC-MS study reported 40 different compounds in COO. n-hexane and methanol extracts of COO demonstrated highest DPPH radical inhibition, with values of 70 and 63.3%, respectively. Extracts of COO in solvents, namely 1-butanol, methanol, diethyl ether, and n-hexane significantly inhibited the proliferation of four pathogenic viruses. Maximum zone of inhibition was observed for Escherichia coli (13.65 ± 0.57 mm). These findings suggest that COO possesses potent antioxidant and antimicrobial properties against viral and bacterial strains, thanks to its biologically active components having no side effects. Further studies are essential to isolate and identify individual bioactive compounds present in COO and to investigate their potential as therapeutic agents.
Teratogenic and embryotoxic effect of diclofenac sodium (DS) on different developmental stages of the chick-embryos was investigated by examining different parameters such as its mortality rate, hatching, morphological measurements, weighing its internal organs and calculation of different indices. Experiment was divided into four trials with different dose (0.1â¯mL, 0.2â¯mL, 0.3â¯mL in groups A, B, and C, respectively and group D received 0.3â¯mL saline solution (0.9% NaCl) and group E remained un-injected) administration and observation. Results of first and second trial showed statistically (p<0.01) significant difference in bodyweight, body-length, forelimb and hindlimb length between experimental and control groups. In third trial, diclofenac sodium administration showed a statistically (p<0.01) significant difference in the bodyweight, body-length, forelimb, hindlimb length, liver weight, egg weight (EE ratio) and kidney somatic index (KSI). The beak-size, heart weight, kidney weight, cardiac somatic index (CSI) and hepato somatic index (HSI) were not significant (p>0.05) when compared with the control groups. In trial 4, forelimb, hindlimb length, heart weight, CSI and HSI were statistically (p<0.01) significant. Body-length and liver weight were significant (p<0.05). While bodyweight, beak size, kidney weight and KSI were non-significant (p>0.05). The mortality rate was increased with increase dose of DS and also affected the hatching. DS effect on chick embryos can be applied to humans because the early development of mammals and birds are closely related. So, it was concluded that DS should be used with caution during pregnancy especially during first trimester of pregnancy.
Cryopreservation is one of the reliable techniques for long-term storage of sperm. The success of this technique depends on the choice of cryoprotectant; therefore, a plethora of literature has reported the effects of different cryoprotective agents so far. Kappa-carrageenan (κ-carrageenan) is a hydrocolloid polysaccharide extracted from red marine seaweed. Its unique property makes it a promising option as a non-colligative cryoprotectant. The current study aims to evaluate the cryoprotective effect of k-carrageenan along with glycerol on ram sperm quality both after equilibration and freezing. Nine Kajli rams were utilized in this experiment for semen collection through an artificial vagina maintained at 42°C. Qualified samples were diluted in tris egg yolk glycerol (TEYG) extender containing different concentrations of k-carrageenan as 0 mg/mL (control), 0.2, 0.5, 0.8 and 1 mg/mL. Post-thaw assessment was done at 37°C after 24 h of storage, which showed a significant improvement (p < .05) in sperm viability, motility, membrane and acrosome integrity in an extender containing k-carrageenan at a concentration of 0.5 mg/mL compared to control. It is concluded from the current study that the combination of glycerol and 0.5 mg/mL concentration of k-carrageenan improved the sperm post-thaw quality.
Semen Preservation , Semen , Male , Sheep , Animals , Carrageenan/pharmacology , Glycerol/pharmacology , Sperm Motility , Spermatozoa , Cryoprotective Agents/pharmacology , Cryopreservation/veterinary , Cryopreservation/methods , Sheep, Domestic , Semen Preservation/veterinary , Semen Preservation/methods , Dietary Supplements
Countries face exasperating and inclement climate worldwide. Food and feed security could be their paramount life objective. The study aimed to investigate the impact of selenium on the protein content and distribution in different parts of rice. For this purpose, advanced selenium biofortified breeding material developed after generations of breeding efforts was investigated at the field area, rice research institute, Chengdu, China during cropping season 2021-22. The accumulation and distribution of selenium and protein contents were observed in various fractions of selenium-enriched rice (Z3057B) and positive control (727). The correlation studies for selenium and protein quantification leads to the optimization of the breeding material and relevance in virtue. The rice fractions indicated rice embryo retains highest selenium contents, which gradually decreases in succession (other rice parts). The difference in protein content between the embryo and endosperm of Se-enriched rice is significant, while that between embryo and aleurone layer is not obvious. The selenium protein was found with molecular weight of 13.6-122.6 kDa. The protein of each molecular weight is found to bind with selenium, but the binding strength of selenium is negatively correlated with the molecular weight of protein. The 67.5% of the total selenium sticks with protein having molecular weight less than 38.8 kDa. In summary, protein with low molecular weight (13.4 kDa) binds maximum selenium and accounts for highest total protein content (40.76%).
Background: Primary health care services to promote the mental and physical health of communities include preventive, promotive, curative, general hygiene, and nutritional elements. Aim: To assess the quality of service delivery at primary healthcare settings in Punjab, Pakistan. Methods: Quantitative surveys were conducted at 106 health facilities: 92 basic health units (BHUs) and 14 rural health centres (RHCs) across Punjab in 2020. Data from the survey were supplemented with information from observations by the researchers and all data were analysed using SPSS version 25. Findings: All the 7 district health authorities surveyed had monthly targets for number of normal deliveries and the outpatient department. Systems for safe transportation and storage of medicines were deficient except in 2 districts. Anti-venom and anti-rabies vaccines were either limited or not available at most of the health units visited. Some 14% of clinical equipment examined at the BHUs and RHCs were non-functional, and no BHU had ultrasonic machines to improve the quality of antenatal care. Sterilization of surgical instruments was unsatisfactory at most health units. Several key positions at BHU and RHC were vacant. Most health units did not have fence and their main buildings were in poor condition. Conclusions: Several gaps were identified at the primary healthcare level in Punjab that need to be addressed to improve the quality of service delivery.
Primary Health Care , Rural Health Services , Humans , Pregnancy , Female , Pakistan , Prenatal Care , Cross-Sectional Studies , Health Services Accessibility , Quality of Health Care
Hexavalent chromium (Cr (VI)) is a hazardous heavy metal that induces hepatotoxicity and nephrotoxicity. Thus, this study was planned to explore the ameliorating capacity of Aloe vera leaf gel extract (AV) and their conjugated silver nanoparticles (AVNP) against Cr (VI) induced hepatotoxicity and renal toxicity. The organ indices, level of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, total protein, and creatinine in blood serum were measured. The histopathological and micrometric analysis of the hepatic and renal tissue sections were studied. The hepatosomatic index was raised significantly (0.098 ± 0.13 g) in Cr treated group. The blood serum level of AST (484 ± 10.7 U/L), ALT (163 ± 5.5 U/L), ALP (336.7 ± 9.5 U/L), MDA (642.3 ± 28.3 U/L), and creatinine (4.0 ± 0.1 mg/dL) were increased significantly, whereas total protein level was declined (2.8 ± 0.3 g/dL) significantly in Cr exposed group. In the histopathological study, necrosis, disturbed hepatic cords, impaired glomeruli, and Bowman's capsule were noted. Micrometric data from the liver and kidney revealed a significant surge in the size of hepatocytes and their nuclei (1188.2 ± 467.7 µ2 and 456.5 ± 205.6 µ2) and CSA of glomeruli and Bowman's capsule (9051.8 ± 249.8 µ2 and 11,835.5 ± 336.7 µ2) in Cr (VI) exposed group, whereas the brush border (10.2 ± 4.0 µ) size declined significantly. The administration of AV and AVNP reduced the oxidative stress induced by Cr (VI).
Infectious bronchitis virus (IBV) is a respiratory virus causing atropism in multiple body systems of chickens. Recently, the California 1737/04 (CA1737/04) IBV strain was identified as one of the circulating IBV variants among poultry operations in North America. Here, the pathogenicity and tissue tropism of CA1737/04 IBV strain in specific-pathogen-free (SPF) hens were characterized in comparison to Massachusetts (Mass) IBV. In 30 weeks-old SPF hens, Mass or CA1737/04 IBV infections were carried out, while the third group was maintained as a control group. Following infection, we evaluated clinical signs, egg production, viral shedding, serology, necropsy examination, and histopathology during a period of 19 days. Also, certain tissue affinity parameters were investigated, which involved the localization of viral antigens and the detection of viral RNA copies in designated tissues. Our findings indicate that infection with CA1737/04 or Mass IBV strain could induce significant clinical signs, reduced egg production, and anti-IBV antibodies locally in oviduct wash and systemically in serum. Both IBV strains showed detectable levels of viral RNA copies and induced pathology in respiratory, renal, enteric, and reproductive tissues. However, the CA1737/04 IBV strain had higher pathogenicity, higher tissue tropism, and higher replication in the kidney, large intestine, and different segments of the oviduct compared to the Mass IBV strain. Both IBV strains shed viral genome from the cloacal route, however, the Mass IBV infected hens shed higher IBV genome loads via the oropharyngeal route compared to CA1737/04 IBV-infected hens. Overall, the current findings could contribute to a better understanding of CA1737/04 IBV pathogenicity in laying hens.
BACKGROUND: Dietary selenium (Se) deficiency, stemming from low Se concentrations in agricultural products, threatens human health. While Se-containing fertilizers can enhance the Se content in crops, the key factors governing Se biofortification with Se fertilization remain unclear. RESULTS: This study constructed a global meta-analysis dataset based on field experiments comprising 364 entries on Se content in agricultural products and 271 entries on their yield. Random forest models and mixed effects meta-analyses revealed that plant types (i.e., cereals, vegetables, legumes, and forages) primarily influenced Se biofortification, with Se fertilization rates being the next significant factor. The random forest model, which included variables like plant types, Se fertilization rates, methods and types of Se application, initial soil conditions (including Se content, organic carbon content, and pH), soil types, mean annual precipitation, and temperature, explained 82.14% of the variation in Se content and 48.42% of the yield variation in agricultural products. For the same agricultural products, the increase in Se content decreased with higher rates of Se fertilization. The increase in Se content in their edible parts will be negligible for cereals, forages, legumes, and vegetable crops, when Se fertilization rates were 164, 103, 144, and 147 g Se ha-1 , respectively. Conversely, while low Se fertilization rates enhanced yields, high rates led to a yield reduction, particularly in cereals. CONCLUSION: Our findings highlight the need for balanced and precise Se fertilization strategies to optimize Se biofortification benefits and minimize the risk of yield reduction. © 2024 Society of Chemical Industry.
CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme. ACAT1 inhibitors previously shown to modulate cardiovascular diseases are now being implicated in immunotherapy. In the present study, we achieved knockdown of ACAT1 in T cells via RNA interference technology by inserting ACAT1-shRNA into anti-CD19-CAR-T cells. Knockdown of ACAT1 led to an increased cytotoxic capacity of the anti-CD19-CAR-T cells. In addition, more CD69, IFN-γ, and GzmB were expressed in the anti-CD19-CAR-T cells. Cell proliferation was also enhanced in both antigen-independent and antigen-dependent manners. Degranulation was also improved as evidenced by an increased level of CD107a. Moreover, the knockdown of ACAT1 led to better anti-tumor efficacy of anti-CD19 CAR-T cells in the B-cell lymphoma mice model. Our study demonstrates novel CAR-T cells containing ACAT1 shRNA with improved efficacy compared to conventional anti-CD19-CAR-T cells in vitro and in vivo.
Lymphoma, B-Cell , Receptors, Antigen, T-Cell , T-Lymphocytes , Animals , Mice , Acetyltransferases , Immunotherapy, Adoptive , Lymphoma, B-Cell/pathology , Antibodies , Cell Proliferation , RNA, Small Interfering
Software Development based on Scrum Agile in a distributed development environment plays a pivotal role in the contemporary software industry by facilitating software development across geographic boundaries. However, in the past different frameworks utilized to address the challenges like communication and collaboration in scrum agile distributed software development (SADSD) were notably inadequate in transparency, security, traceability, geographically dispersed location work agreements, geographically dispersed teamwork effectiveness, and trust. These deficiencies frequently resulted in delays in software development and deployment, customer dissatisfaction, canceled agreements, project failures, and disputes over payments between customers and development teams. To address these challenges of SADSD, this paper proposes a new framework called ChainAgile, which leverages blockchain technology. ChainAgile employs a private Ethereum blockchain to facilitate the execution of smart contracts. These smart contracts cover a range of functions, including acceptance testing, secure payments, requirement verification, task prioritization, sprint backlog, user story design and development and payments with the automated distribution of payments via digital wallets to development teams. Moreover, in the ChainAgile framework, smart contracts also play a pivotal role in automatically imposing penalties on customers for making late payments or for no payments and penalties on developers for completing the tasks that exceed their deadlines. Furthermore, ChainAgile effectively addresses the scalability limitations intrinsic in blockchain technology by incorporating the Interplanetary File System (IPFS) is used for storage solutions as an off-chain mechanism. The experimental results conclusively show that this innovative approach substantially improves transparency, traceability, coordination, communication, security, and trust for both customers and developers engaged in scrum agile distributed software development (SADSD).
Blockchain , Communication , Dissent and Disputes , Emotions , Software
