Breaking down barriers: The potential of smarter CAR-engineered NK cells against solid tumors.

Natural killer (NK) cells are considered to be the foremost fighters of our innate immune system against foreign invaders and thus tend to promptly latch onto the virus-infected and tumor/cancerous cells, killing them through phagocytosis. At present, the application of genetically engineered Chimeric antigen receptor (CAR) receptors ensures a guaranteed optimistic response with NK cells and would not allow the affected cells to dodge or escape unchecked. Hence the specificity and uniqueness of CAR-NK cells over CAR-T therapy make them a better immunotherapeutic choice to reduce the load of trafficking of numerous tumor cells near the healthy cell populations in a more intact way than offered by CAR-T immunotherapy. Our review mainly focuses on the preclinical, clinical, and recent advances in clinical research trials and further strategies to achieve an augmented and efficient cure against solid tumors.

Hydrogen sulfide mediates defense response in safflower by regulating secondary metabolism, oxidative defense, and elemental uptake under drought.

Hydrogen sulfide (H2 S) is a newly recognized molecule mediating plant defense responses under drought. The role of exogenous H2 S in regulating plant responses under drought has been reported in a few plant species including spinach, wheat, Arabidopsis, soybean, and citrus plants. However, no report is available on the outcome of exogenous H2 S on drought response in safflower plants. Therefore, the present study was planned to get insight into H2 S-mediated regulation of growth, secondary metabolism, oxidative defense, and uptake of minerals in two safflower cultivars (Safflower-16427 and Safflower-16493). Plants were exposed to two NaHS (0.5 and 1.0 mM) and two drought levels (70 and 50% field capacity [FC]). We found a notable depression in growth, yield, chlorophyll, and potassium (K+ ) uptake under drought. The decline was more significant in plants facing 50% FC. The oxidative injury in plants was higher under severe drought and led to the decline in chlorophyll, plant biomass, and yield production. Drought induced a noticeable accretion in the accumulation of total soluble sugars, proline, ascorbic acid, anthocyanins, and secondary metabolites that protect plants against oxidative damages caused by drought. The activities of antioxidant enzymes increased substantially in safflower cultivars under drought. Besides, plants pretreated with NaHS (0.5 mM) subsided the oxidative damage by increasing the accumulation of secondary metabolites and strengthening the antioxidant capacity under drought. Further, drought plants suffered significant disturbances in ions homeostasis that was circumvented by exogenous H2 S. The interactive effect of drought and H2 S did not display a significant difference between the cultivars.

Salicylic Acid and Gemma-Aminobutyric Acid Mediated Regulation of Growth, Metabolites, Antioxidant Defense System and Nutrient Uptake in Sunflower (Helianthus annuus L.) Under Arsenic Stress.

Background: Arsenic (As) is a highly toxic and carcinogenic pollutant commonly found in soil and water, posing significant risks to human health and plant growth. Objective: The objectives of this study to evaluate morphological, biochemical, and physiological markers, as well as ion homeostasis, to alleviate the toxic effects of As in sunflowers through the exogenous application of salicylic acid (SA), γ-aminobutyric acid (GABA), and their combination. Methods: A pot experiment was conducted using two sunflower genotypes, FH-779 and FH-773, subjected to As stress (60 mg kg-1) to evaluate the effects of SA at 100 mg L-1, GABA at 200 mg L-1, and their combination on growth and related physiological and biochemical attributes under As stress. Results: The study revealed that As toxicity had a detrimental effect on various growth parameters, chlorophyll pigments, relative water content, total proteins, and nutrient uptake in sunflower plants. It also led to increased oxidative stress, as indicated by higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), along with As accumulation in the roots and leaves. However, the application of SA and GABA protected against As-induced damage by enhancing the enzymatic antioxidant defense system. This was achieved through the activation of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as an increase in osmolytes. They also improved nutrient acquisition and plant growth under As toxicity. Conclusions: We investigated the regulatory roles of SA and GABA in mitigating arsenic-induced phytotoxic effects on sunflower. Our results revealed a significant interaction between SA and GABA in regulating growth, photosynthesis, metabolites, antioxidant defense systems, and nutrient uptake in sunflower under As stress. These findings provide valuable insights into plant defense mechanisms and strategies to enhance stress tolerance in contaminated environments. In the future, SA and GABA could be valuable tools for managing stress in other important crops facing abiotic stress conditions.

A Pilot Study of Symptoms of Major Depressive Disorder in Medical Students at an Osteopathic Medical School Before and After High-Stakes Examinations.

Background: Given the high prevalence of symptoms of major depressive disorder (MDD) in medical students, identifying factors that impact the development of such symptoms is important. Previous data suggest that medical students can experience symptoms of MDD after medical school exams. It is not known if medical students experience more symptoms of MDD directly before or after exams. The aim of the current study is to determine the prevalence of symptoms of MDD in first- and second-year medical students directly before and after high-stakes medical school examinations. Methods: Two anonymous surveys were sent via REDCap to first- and second-year medical students at the University of New England College of Osteopathic Medicine. A pre-exam survey on the day of the exam asking about the past three days' MDD symptoms, and a post-exam survey sent three days after the exam asking about MDD symptoms experienced after the exam was sent out to a total of 391 students with a response rate of 23%. Results: First- and second-year medical students regardless of gender experienced symptoms of MDD at higher rates before exams than afterwards. Female students experienced symptoms of MDD (as defined by the DSM-5) including sadness, sleep disturbances, and feelings of guilt or worthlessness at a greater rate compared to males before exams. After exams, females were more likely to experience sleep disturbances and decreased energy. Second-year male students were the least likely to experience symptoms of MDD. Conclusion: First- and second-year medical students can experience symptoms of MDD surrounding exams. This study highlights the emotional burden that students may carry near exams. It underscores the importance of further research on this topic to evaluate the effect exams have on the mental health of medical students during their training.

Implication of Prophetic Variables and their Impulsive Interplay in CA Prostate Patients Experiencing Osteo-Metastasis.

AIMS: To identify variables having a critical role in prostate cancer patients experiencing osteometastasis. BACKGROUND: Prostatic carcinoma is a multifactorial complex disorder that exhibits an increased propensity to develop bone metastasis. An interplay of inflammatory and bone remodeling parameters promotes the formation of pre-metastatic niches in bones of patients, which could render them more vulnerable to skeletal disabilities. OBJECTIVE: To evaluate the multi-dynamic inter-relationship of circulating variables in prostate cancer patients experiencing osteo-metastasis. MATERIALS AND METHODS: Fifty-seven (n=57) men with clinically confirmed prostate cancer, fifty-nine (n=59) with skeletal metastases, and one hundred (n=100) healthy subjects i.e., men aging from 53-84 years with no clinical evidence of prostate were recruited from the Jinnah Hospital Lahore, Pakistan. Informed consent was obtained, and a venous blood sample was drawn and stored at -70oC until assayed. Levels of variables were evaluated using appropriate methods. Levels of Matrix Metalloproteinases (MMPs), Osteopontin (OPN), TGH- ß, and sRANKL were estimated by the ELISA method. Each sample was suspended and the given protocol was employed. ELISA readings were obtained for the estimation of all variables. RESULTS: Highly significant (P˂0.05) differential expression of oxidative stress, inflammatory cytokines, and bone remodeling variables were observed in localized and osteo-metastatic CA prostate patients. A strong positive correlation was revealed among OPN, sRANKL, MMP-7, MMP-9, PSA, and TGF-ß (OPN vs. MMP-7, r=0.698* and OPN vs. MMP-9, r=0.765**, OPN vs. RANKL, =0.856*, sRANKL vs. MMP-9, r=0.825**, TGF- ß vs. RANKL, r=0.868* and PSA vs. TGF- ß, r=0.752*); lower levels of OPG were estimated in metastasized patients, showing that both osteolytic and osteoblastic phases of bone remodeling occur simultaneously. CONCLUSION: The altered oxidative and inflammatory responses endorse Matrix Metalloproteinases (MMPs) increased activity, RANKL/OPG imbalance, and enhanced bone matrix proteins turnover, which can foster the process of osteo-metastasis. The perturbed RANKL/OPG drift and enhanced PSA levels are associated with increased TGF-ß activity to aggravate Epithelial Mesenchymal transition (EM) and osteo-tropism of prostate cancer. Thus, designing novel targets of these major variables can minimize the incidence of prostate cancer patients.

Design and Development of a Wideband Planar Yagi Antenna Using Tightly Coupled Directive Element.

In this paper, a novel concept on the design of a broadband printed Yagi antenna for S-band wireless communication applications is presented. The proposed antenna exhibits a wide bandwidth (more than 48% fractional bandwidth) operating in the frequency range 2.6 GHz-4.3 GHz. This is achieved by employing an elliptically shaped coupled-directive element, which is wider compared with other elements. Compared with the conventional printed Yagi design, the tightly coupled directive element is placed very close (0.019λ to 0.0299λ) to the microstrip-fed dipole arms. The gain performance is enhanced by placing four additional elliptically shaped directive elements towards the electromagnetic field's direction of propagation. The overall size of the proposed antenna is 60 mm × 140 mm × 1.6 mm. The proposed antenna is fabricated and its characteristics, such as reflection coefficient, radiation pattern, and gain, are compared with simulation results. Excellent agreement between measured and simulation results is observed.

Symptomatic hyperammonemia after lung transplantation: lessons learnt.

Hyperammonemia, post-orthotopic lung transplantation, is a rare but mostly fatal complication. Various therapies, including those to decrease ammonia generation, increase nitrogen excretion, and several dialytic methods for removing ammonia have been tried. We describe three lung transplant recipients who developed acute hyperammonemia early after transplantation. Two of the three patients survived after a multidisciplinary approach including discontinuation of drugs, which impair urea cycle, aggressive ammonia reduction with prolonged daily intermittent hemodialysis (HD), and overnight slow low-efficiency dialysis in conjunction with early weaning of steroids and other therapeutic measures. Our experience suggests that early initiation of dialysis, high dialysis dose, increased frequency, and HD preferably to less efficient modalities increases survival in these patients.