Ionic reverberation modulates the cellular fate of CD8+tissue resident memory T cells (TRMs) in patients with renal cell carcinoma: A novel mechanism.

In metastatic renal cell carcinoma (mRCC), existing treatments including checkpoint inhibitors are failed to cure and/or prevent recurrence of the disease. Therefore, in-depth understanding of tumor tissue resident memory T cells (TRMs) dysfunction are necessitated to enrich efficacy of immunotherapies and increasing disease free survival in treated patients. In patients, we observed dysregulation of K+, Ca2+, Na2+ and Zn2+ ion channels leads to excess infiltration of their respective ions in tumor TRMs, thus ionic gradients are disturbed and cells became hyperpolarized. Moreover, overloaded intramitochondrial calcium caused mitochondrial depolarization and trigger apoptosis of tumor TRMs. Decreased prevalence of activated tumor TRMs reflected our observations. Furthermore, disruptions in ionic concentrations impaired the functional activities and/or suppressed anti-tumor action of circulating and tumor TRMs in RCC. Collectively, these findings revealed novel mechanism behind dysfunctionality of tumor TRMs. Implicating enrichment of activated TRMs within tumor would be beneficial for better management of RCC patients.

Comparison of In-Hospital Outcomes between Early and Late Catheter-Directed Thrombolysis in Acute Pulmonary Embolism: A Retrospective Observational Study.

The purpose of this study is to evaluate whether early initiation of catheter-directed thrombolysis (CDT) in patients presenting with acute pulmonary embolism is associated with improved in-hospital outcomes. A retrospective cohort was extracted from the 2016-2019 National Inpatient Sample database, consisting of 21,730 weighted admissions undergoing CDT acute PE. From the time of admission, the sample was divided into early (<48 h) and late interventions (>48 h). Outcomes were measured using regression analysis and propensity score matching. No significant differences in mortality, cardiac arrest, cardiogenic shock, or intracranial hemorrhage (p > 0.05) were found between the early and late CDT groups. Late CDT patients had a higher likelihood of receiving systemic thrombolysis (3.21 [2.18-4.74], p < 0.01), blood transfusion (1.84 [1.41-2.40], p < 0.01), intubation (1.33 [1.05-1.70], p = 0.02), discharge disposition to care facilities (1.32 [1.14-1.53], p < 0.01). and having acute kidney injury (1.42 [1.25-1.61], p < 0.01). Predictors of late intervention were older age, female sex, non-white ethnicity, non-teaching hospital admission, hospitals with higher bed sizes, and weekend admission (p < 0.01). This study represents a comprehensive evaluation of outcomes associated with the time interval for initiating CDT, revealing reduced morbidity with early intervention. Additionally, it identifies predictors associated with delayed CDT initiation. The broader ramifications of these findings, particularly in relation to hospital resource utilization and health disparities, warrant further exploration.

Clinical significance of blocking novel immune checkpoint B7-H4 in urothelial carcinoma of bladder as a potential therapeutic target.

Urothelial Carcinoma of Bladder is complex disease with high mortality and recurrence rates. Current standard regimes have exhibited anti-tumor activity but still, a proportion of patients are non-responsive or in-eligible to receive such treatments. Immune checkpoints have emerged as potential class of therapeutics to be tested in UCB patients. Clinical trials targeting PD-1/PD-L1 axis have been tested in UCB but still a proportion of patients are non-responsive to it which stresses upon identifying new targets. New immune checkpoint B7-H4 has been shown to negatively regulate T cell activity in cancer and is a poor prognostic factor in various solid tumors. In this study we assessed the novel immune checkpoint B7-H4 status in UCB patients. We observed elevated expression of B7-H4 and PD-L1 on CD8+ T cells in circulation of UCB patients. Relative mRNA expression and immunohistochemistry displayed upregulation in bladder tumor tissue. Increased expression of B7-H4 along with PD-L1 in periphery and tumor of UCB patients highlights involvement of B7-H4 in disease progression. Combinatorial blocking of B7-H4 and PD-L1 enhanced IFN-γ and granzyme B in CD8+ T cells functional T cell immune response in UCB patients. Also, B7-H4 was significantly associated with clinico-pathological parameters. Our findings highlight B7-H4 as potential therapeutic target for treatment of UCB patients in future after further validation.

Management conundrum in a case of renal cell cancer (RCC) on dual antiplatelet therapy (DAPT) for recently placed coronary drug-eluting stent (DES).

A man in his 50s presented in an emergency with breathlessness and chest discomfort. On evaluation, he was diagnosed with coronary artery disease, with more than 80% narrowing of the right coronary and left circumflex arteries. The patient underwent percutaneous coronary intervention and was started on dual antiplatelet (DAPT) therapy. After starting DAPT, the patient developed gross haematuria with a drop in haematocrit. Further evaluation revealed a left renal mass with urinary bladder clots. Because of the risk of stent thrombosis on stopping DAPT, radical nephrectomy was deferred, and the patient underwent left renal artery angioembolisation and bladder clot evacuation. On the follow-up, the patient was stable with a gradual decrease in renal mass size, and after a year, the patient underwent definitive surgery. The patient is doing well in 4 years of follow-up with no metastasis.

Serum prostate-specific antigen trends and prostate cancer detection on follow-up in men with a prior negative biopsy: A cohort study.

Introduction: Elevated serum prostate-specific antigen (PSA) is the most common trigger for a prostate biopsy. However, the range of normal PSA is poorly defined in many populations. Men with "elevated" PSA may not harbor cancer, and it is unclear if such men with a prior negative prostate biopsy should be biopsied again. We conducted a cohort study to assess the PSA trends and cancer detection rates in such men. Methods: In an Institutional Review Board-approved ambispective study, men who underwent prostate biopsy between January 2016 and December 2021 for PSA > 4 ng/mL were identified. Among them, those whose biopsy was negative for malignancy were contacted either telephonically or reviewed in person, and the most recent PSA and histopathology of any repeat prostate biopsy were determined. These were evaluated to assess the PSA trend, re-biopsy rate, and cancer detection rate. Results: During the study period, prostate biopsies were performed in a total of 1260 men; out of which 444 were negative for malignancy and 241 patients fulfilled the inclusion criteria. Their median prebiopsy PSA was 9.81 ng/mL (interquartile range [IQR]: 7.14-15.6), and the median follow-up PSA was 5.08 (IQR: 3.18-8.4). At a median follow-up of 53 months (range: 6-77 months), PSA had decreased in 177 (73.4%) patients, was static in 48 (19.9%) patients, and increased in only 16 (6.6%) patients. Repeat biopsy was performed on 20 patients; of whom seven had cancer (35%) with an overall positivity rate of 2.9% among the 241 patients. Although the positivity rate was higher in men with increased PSA, it was not statistically different from those with lower or similar PSA. No factors could be identified to predict a positive repeat biopsy. Conclusions: PSA, the sole trigger for a prostate biopsy, declined in nearly three-quarters of men with a negative first biopsy, and <3% of men were detected to have cancer on a repeat biopsy. This information could help appropriately counsel patients and allay anxiety after a negative biopsy.

Institute for Clinical and Economic Review - Peterson Health Technology Institute value assessment framework for digital health technologies.

Digital health technologies (DHTs) are a broad and rapidly innovating class of interventions with distinctive pathways for development, regulatory approval, uptake and reimbursement. Given the unique nature of DHTs, existing value assessment frameworks and evidence standards for health technologies such as drugs and devices are not directly applicable. The value assessment framework presented here describes a conceptual model and associated methods to guide assessments of DHTs. The framework seeks to accomplish two goals: to set evidence standards that guide technology developers to generate robust evidence on their products; and to provide reviews that help organizations adopt high-impact DHTs with the strongest evidence for delivering improved clinical outcomes and cost savings. This assessment framework will serve as the roadmap for future evaluations of DHTs by the Institute for Clinical and Economic Review (ICER) and the Peterson Health Technology Institute (PHTI). We believe that all stakeholders will benefit from comprehensive and explicit standards of evidence on the different dimensions necessary to understand the value of DHTs.

Material matters: exploring the interplay between natural biomaterials and host immune system.

Biomaterials are widely used for various medical purposes, for instance, implants, tissue engineering, medical devices, and drug delivery systems. Natural biomaterials can be obtained from proteins, carbohydrates, and cell-specific sources. However, when these biomaterials are introduced into the body, they trigger an immune response which may lead to rejection and failure of the implanted device or tissue. The immune system recognizes natural biomaterials as foreign substances and triggers the activation of several immune cells, for instance, macrophages, dendritic cells, and T cells. These cells release pro-inflammatory cytokines and chemokines, which recruit other immune cells to the implantation site. The activation of the immune system can lead to an inflammatory response, which can be beneficial or detrimental, depending on the type of natural biomaterial and the extent of the immune response. These biomaterials can also influence the immune response by modulating the behavior of immune cells. For example, biomaterials with specific surface properties, such as charge and hydrophobicity, can affect the activation and differentiation of immune cells. Additionally, biomaterials can be engineered to release immunomodulatory factors, such as anti-inflammatory cytokines, to promote a tolerogenic immune response. In conclusion, the interaction between biomaterials and the body's immune system is an intricate procedure with potential consequences for the effectiveness of therapeutics and medical devices. A better understanding of this interplay can help to design biomaterials that promote favorable immune responses and minimize adverse reactions.

Impact of manures and fertilizers on yield and soil properties in a rice-wheat cropping system.

The use of chemical fertilizers under a rice-wheat cropping system (RWCS) has led to the emergence of micronutrient deficiency and decreased crop productivity. Thus, the experiment was conducted with the aim that the use of organic amendments would sustain productivity and improve the soil nutrient status under RWCS. A three-year experiment was conducted with different organic manures i.e. no manure (M0), farmyard manure @ 15 t ha-1 (M1), poultry manure @ 6 t ha-1(M2), press mud @ 15 t ha-1(M3), rice straw compost @ 6 t ha-1(M4) along with different levels of the recommended dose of fertilizer (RDF) i.e. 0% (F1), 75% (F2 and 100% (F3 in a split-plot design with three replications and plot size of 6 m x 1.2 m. Laboratory-based analysis of different soil as well as plant parameters was done using standard methodologies. The use of manures considerably improved the crop yield, macronutrients viz. nitrogen, phosphorus, potassium and micronutrients such as zinc, iron, manganese and copper, uptake in both the crops because of nutrient release from decomposed organic matter. Additionally, the increase in fertilizer dose increased these parameters. The system productivity was maximum recorded under F3M1 (13,052 kg ha-1) and results were statistically identical with F3M2 and F3M3. The significant upsurge of macro and micro-nutrients in soil and its correlation with yield outcomes was also observed through the combined use of manures as well as fertilizers. This study concluded that the use of 100% RDF integrated with organic manures, particularly farmyard manure would be a beneficial resource for increased crop yield, soil nutrient status and system productivity in RWCS in different regions of India.

Association of heavy metals and trace elements in carcinoma urinary bladder: A case-controlled study.

Introduction: Abnormal levels of heavy metals (HM) and trace elements (TE) affect body metabolism and can induce carcinogenesis. This study aims to evaluate the role of HM and TE in carcinoma urinary bladder (CAUB). Methods: Patients with biopsy-proven CAUB (n = 100) were taken as the study group, while age-and sex-matched healthy volunteers were taken as control (n = 100). Blood and urine samples were compared for Arsenic (As), Copper (Cu), Manganese (Mn), Selenium (Se), Cadmium (Cd), Lead (Pb), and Mercury (Hg) levels. Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and lipid peroxidation (LPO) levels were assessed to know the redox status between the two groups. Results: A significantly higher blood level of As, Mn, and Pb was observed in CAUB cases as compared to controls. Blood Se level was significantly lower in CAUB patients. On comparing urinary levels, CAUB patients had a higher As, Mn, and Pb levels compared to controls. Further, 68% and 59% of patients had their blood and urinary HM and TE levels above the permitted level, respectively. CAUB cases also had a lower GSH-Px (113.5 ± 44.7 vs. 163.9 ± 120.5, P = 0.0002), lower SOD levels (11.35 ± 5.6 vs. 13.75 ± 3.9, P = 0.008), and a higher LPO levels (15.5 ± 14.7 vs. 11.18 ± 11.2, P = 0.02) in the serum. Conclusions: A significantly higher concentration of As, Mn, and Pb was noted in the blood and urine of CAUB patients compared to controls. CAUB cases also had lower serum GSH-Px and SOD levels with a concomitant increased serum LPO assay suggesting underlying oxidative stress.

Quality of life assessment in testicular non-seminomatous germ cell tumour survivors.

PURPOSE: Patients with Germ cell tumours (GCT) are at risk of long-term toxicities due to multimodality therapy. It is debatable whether there is an impact on the quality of life(QoL) of GCT survivors. METHODS: A case-control study was conducted at a tertiary care centre in India, using the EORTC QLQ C30 questionnaire, to compare the QoL between GCT survivors(disease free > 2 years) and healthy matched controls. A multivariate regression model was used to identify factors affecting QoL. RESULTS: A total of 55 cases and 100 controls were recruited. Cases had a median age of 32 years (interquartile range, IQR 28-40 years), ECOG PS of 0-1(75%), advanced stage III (58%), chemotherapy (94%) and 66% were > 5 years from diagnosis. The median age of controls: 35 years (IQR 28-43 years). A statistically significant difference was seen for emotional (85.8 ± 14.2 vs 91.7 ± 10.4, p 0.005), social(83.0 ± 22.0 vs 95.2 ± 9.6, p < 0.001) and global scales (80.4 ± 21.1 vs 91.3 ± 9.7, p < 0.001). Cases had more nausea and vomiting(3.3 ± 7.4 vs 1.0 ± 3.9, p 0.015), pain(13.9 ± 13.9 vs 4.8 ± 9.8, p < 0.001), dyspnea(7.9 + 14.3 vs 2.7 ± 9.1, p 0.007), and appetite loss(6.7 ± 14.9 vs 1.9 ± 7.9, p 0.016) and greater financial toxicity(31.5 ± 32.3 vs 9.0 ± 16.3, p < 0.001). Adjusting for age, performance status, BMI, stage, chemotherapy, RPLND, recurrent disease, and time since diagnosis, no predictive variables were significant. CONCLUSION: There is a detrimental impact of history of GCT in long term survivors of GCT.

Minerals and chelated-based manganese fertilization influences the productivity, uptake, and mobilization of manganese in wheat (Triticum aestivum L.) in sandy loam soils.

Manganese (Mn) is an essential micronutrient in plants, and it is necessary for hydrolysis in photosystem II, chlorophyll biosynthesis, and also chloroplast breakdown. Limited Mn availability in light soil resulted in interveinal chlorosis, poor root development, and the development of fewer tillers, particularly staple cereals including wheat, while foliar Mn fertilizers were found efficient in improving crop yield as well as Mn use efficiency. In the above context, a study was conducted in consecutive two wheat growing seasons for screening of the most effective and economical Mn treatment for improving the yield and Mn uptake in wheat and to compare the relative effectiveness of MnCO3 against the recommended dose of MnSO4 for wheat. To fulfill the aims of the study, three manganese products, namely, 1) manganese carbonate MnCO3 (26% Mn w/w and 3.3% N w/w), 2) 0.5% MnSO4·H2O (30.5% Mn), and 3) Mn-EDTA solution (12% Mn), were used as experimental treatments. Treatments and their combinations were as follows: two levels of MnCO3 (26% Mn) @ 750 and 1,250 ml ha-1 were applied at the two stages (i.e., 25-30 and 35-40 days after sowing) of wheat, and three sprays each of 0.5% MnSO4 (30.5% Mn) and Mn-EDTA (12% Mn) solution were applied in other plots. The 2-year study showed that Mn application significantly increased the plant height, productive tillers plant-1, and 1,000 grain weight irrespective of fertilizer source. The results of MnSO4 for grain yield wheat as well as uptake of Mn were statistically at par with both levels (750 and 1,250 ml ha-1) of MnCO3 with two sprays at two stages of wheat. However, the application of Mn in the form of 0.5% MnSO4·H2O (30.5% Mn) was found more economical than MnCO3, while the mobilization efficiency index (1.56) was found maximum when Mn was applied in MnCO3 with two sprays (750 and 1,250 ml ha-1) in the two stages of wheat. Thus, the present study revealed that MnCO3 can be used as an alternative to MnSO4 to enhance the yield and Mn uptake of wheat.

Disruption in networking of KCMF1 linked ubiquitin ligase impairs autophagy in CD8+ memory T cells of patients with renal cell carcinoma.

Metastatic Renal Cell Carcinoma (mRCC) remains incurable, despite the current checkpoint-blockade-driven, limited overall response rate. The CD8+ memory T cells can mount a rapid and an effective response. The ubiquitin ligase RAD6-KCMF1-UBR4-mediated regulation of autophagy in CD8+ memory T cells in patients with renal cell carcinoma (RCC) remains unexplored. Consequently, flow cytometry was used to study memory T cells, and their subsets, including activation and regulatory phenotypes in peripheral blood mononuclear cells (PBMCs). Expression of the ubiquitin ligase and autophagy was measured both at the cellular and molecular levels in memory T cells of patients with RCC. JC.1 staining and Annexin/PI assays were used to evaluate the memory T cells depolarization and apoptosis rates. The results indicated that the disruption of Ub-E2-E3 complex and impaired autophagy in memory T cells diminished their ability to survive and combat against tumor cells. Inhibition of memory T cells apoptosis by targeting E3 ubiquitin ligase or autophagy pathways can be explored as a potential therapeutic strategy to improve the long-term survival of memory T cells in RCC.

Biofortification of mungbean (Vigna radiata L. (Wilczek)) with boron, zinc and iron alters its grain yield and nutrition.

Mungbean [Vigna radiata L. (Wilczek)] is considered as an extremely nutritious crop possessing a high level of micronutrients, but their low bioavailability in the crop leads to micronutrient malnutrition in humans. Therefore, the present study was conducted to investigate the potential of nutrients viz. boron (B), zinc (Zn) and iron (Fe) biofortification on productivity, nutrient concentration and uptake as well as the economics of mungbean cultivation. In the experiment, the various combinations of RDF with ZnSO4.7H2O (0.5%), FeSO4.7H2O (0.5%) and borax (0.1%) were applied to mungbean variety ML 2056. The combined foliar application of Zn, Fe and B was highly efficient in increasing the yield of grain as well as straw in mungbean exhibiting maximum values i.e. 944 kg ha-1 and 6133 kg ha-1, respectively. Similar results for B, Zn and Fe concentration in grain (27.3 mg kg-1, 35.7 mg kg-1 and 187.1 mg kg-1, respectively) and straw (21.1 mg kg-1, 18.6 mg kg-1 and 376.1 mg kg-1, respectively) of mungbean were observed. Also, uptake of Zn and Fe by grain (31.3 g ha-1 and 164.4 g ha-1, respectively), as well as straw (113.7 g ha-1 and 2295.0 g ha-1, respectively), was maximum for the above treatment. Whereas, the B uptake was found to enhance significantly through the combined application of B, Zn and Fe, where the values 24.0 g ha-1 and 128.7 g ha-1 corresponded to grain and straw, respectively. Thus, combined use of ZnSO4.7H2O (0.5%) + FeSO4.7H2O (0.5%) and borax (0.1%) significantly improved the yield outcomes, the concentration of B, Zn and Fe, uptake and economic returns of mungbean cultivation to alleviate the B, Zn and Fe deficiency.

Interactive effect of land use systems on depth-wise soil properties and micronutrients minerals in North-Western, India.

Micronutrients play a vital role in improving growth and performance of different crops. Management of soil micronutrients for better crop production needs sound understanding of their status and causes of variability. Therefore, in order to evaluate the changes in soil properties and micronutrient contents of soils, an experiment was conducted with soil samples from six soil depths i.e. 0-10, 10-20, 20-40,40-60, 60-80 and 80-100 cm of four prominent land-use systems viz. forest, horticulture, crop land and barren land. Amongst these, the maximum contents of OC (0.36%), clay (19.4%), DTPA-Zn (1.14 mg kg-1), Fe (11.78 mg kg-1), Mn (5.37 mg kg-1), Cu (0.85 mg kg-1) and Ni (1.44 mg kg_1) were observed in soils of forest land use system followed by horticulture, crop land and barren land, respectively. Also, soils of forest landpossessed 29.5, 21.3, 58.4, 51.8 and 44.0% higher DTPA-Zn, Fe, Mn, Cu and Ni as compared to crop land use system. Interactive influence of land use systems and soil depths on distribution of DTPA extractable micronutrients was found to be positive with maximum content at 0-10 cm depth of forest land use and lowest at 80-100 cm of barren land use system, respectively. Correlation analysis explicit positive and significant relationship of OC with DTPA Zn (r = 0.81), Fe (r = 0.79), Mn (r = 0.77), Cu (r = 0.84) andNi (r = 0.80), whereas the correlation results among DTPA micronutrients indicated the highest positivecorrelation of Ni with Cu (r = 0.95) and Mn (r = 0.93) followed by Fe with Zn (r = 0.93). Therefore, inclusion of forest and horticulture land use in crop lands or shift of land use from forest based to crop land resulted in renewal of degraded soil which could be beneficial for enhancing agricultural sustainability.

Effect of addition of organic manures on basmati yield, nutrient content and soil fertility status in north-western India.

Integrated use of chemical fertilizers with organic manure is becoming a quite promising practice to maintain higher crop productivity and to manage soil health, which is otherwise deteriorated due to intensive cultivation and imbalanced fertilizer use. Thus, the present experiment was conducted for combined application of inorganic fertilizers and organic manures for higher yield and nutrient uptake in basmati rice as well as to restore soil health. The treatments applied in the present study involve T1: control, T2: Farmyard manure (15 t ha-1), T3: Poultry manure (6 t ha-1), T4: Press mud (15 t ha-1), T5: Rice straw compost (6 t ha-1), T6: Farmyard manure (15 t ha-1) + 50% N (recommended dose of nitrogen), T7: Poultry manure (6 t ha-1) + 50% N, T8: Press mud (15 t ha-1) + 50% N, T9: Rice straw compost (6 t ha-1) + 50% N, T10: 75% N, T11: Farmyard manure (15 t ha1) + 75% N, T12: Poultry manure (6 t ha-1) + 75% N, T13: Press mud (15 t ha-1) + 75% N, T14: Rice straw compost (6 t ha-1) + 75% N, T15: 100% N. The integrated use of organic manures and inorganic fertilizers significantly increased the grain and straw yield, macronutrients as well as micronutrients uptake in basmati due to the release of nutrients from decomposition of organic manures. Among different treatments, the addition of PM+75% N showed maximum grain yield, straw yield and sustainability yield index (44.53 q ha-1, 89.67 q ha-1 and 0.91 respectively) as well as the highest uptake of nitrogen (58.29 and 65.39 kg ha-1), phosphorus (25.04 and 23.24 kg ha-1) and potassium (15.26 and 118.95 kg ha-1) in grain and straw, respectively. Similar results were observed for zinc (Zn), copper (Cu), iron (Fe) and manganese (Mn) uptake under treatment involving PM+75% N with values 183.9, 26.18, 339.3 and 355.8 g ha-1 in grain and 205.3, 25.62, 2627.3 and 278 g ha-1 in straw, respectively. Additionally, correlation studies showed that the grain and straw yield of basmati exhibited a significantly positive correlation with soil P, Cu and Fe. The study suggested that the partial substitution of inorganic fertilizers with organic manures did not lower crop yield and nutrient uptake. Thus, integrated application of organic and inorganic fertilizers can be used for the sustainability of basmati-wheat system and to retain the soil fertility which is otherwise deteriorated with sole use of inorganic fertilizers.

A Large Contemporary Experience of Renal Tumors in Young: Clinico-pathological Profile and Long-Term Survival Patterns.

Renal tumors in young population are relatively rare. We reviewed our experience with renal masses in patients below 45 years of age. Our objective was to analyze clinico-pathological and survival characteristics of renal malignancy in young adults in contemporary era. The medical records of patients below 45 years of age who underwent surgery for renal mass at our tertiary care center between 2009 and 2019 were retrospectively analyzed. Pertinent clinical information was compiled, including age, gender, year and type of surgery, histopathology and survival data. A total of 194 patients who underwent nephrectomy for suspicious renal masses were included. Mean age was 35.5 (14-45) years and males were 125 (64.4%). A total of 29/198 (14.6%) specimens had benign disease. In addition, 155 (91.7%) out of 169 malignant tumors were renal cell carcinomas, clear cell variant being the most common type (51%). Compared to RCC, non-RCC tumors were more common in females (27.7 vs 78.6%, p < 0.0001), had an early age of diagnosis (27.2 vs 36.9 year, p < 0.00001) and poorer progression-free (58.3 vs 72.0%, p = 0.03) and overall survival (63.6 vs 84.2%, p = 0.02) at 6 years of follow-up. Renal masses in young adults are most commonly RCC but can also include other diverse types. RCC in young adults is usually organ confined and has good prognosis. As compared to RCC, non-RCC malignant tumors occur in young age, are more in females, and have worse prognosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01643-2.

Prepubic inflammatory liposarcoma presenting as urosepsis.

Inflammatory well-differentiated liposarcoma is a rare soft-tissue tumor which is predominantly retroperitoneal in origin. We report a 72-year-old male without co-morbidities with suspected urosepsis and an obstructing ureteric calculus. Despite adequate diversion and broad-spectrum antimicrobials, the leukocytosis persisted. Further imaging revealed a locally infiltrating prepubic mass which was suspicious of a lymphoid malignancy and was found to be a high-grade liposarcoma on biopsy. He underwent open wide local resection of the tumor and the histopathology revealed an inflammatory well-differentiated liposarcoma with areas of neutrophilic abscess and necrosis. A dramatic response to the surgical resection was seen and the leukocytosis resolved within a few days.

Agronomic biofortification of forage crops with zinc and copper for enhancing nutritive potential: a systematic review.

Many developing countries are facing a silent increase in deficiency of micronutrients in forage crops that results in decreased levels of essential nutrients in animals. Micronutrients are essential not only for basic metabolic processes of forage crops but also for sustaining animal health. Forage productivity and quality are severely affected by soil micronutrients deficiencies, especially zinc and copper. This review summarizes the literature highlighting the significance of different methodologies used to increase the biomass and quality of forage so as to enhance the micronutrient content of the forage crops through biofortification. Biofortification is a promising and sustainable agriculture-based strategy to reduce micronutrient deficiency in crops. The experiments and trials conducted at different locations of the world showed that copper and zinc concentrations in animal fodders can be enhanced through the process of foliar application. Additionally, agronomic biofortification showed more promising results, and thus is an outstanding, fast, and cost-effective technique for the immediate enrichment of forage in order to overcome malnutrition in animals. © 2022 Society of Chemical Industry.

KCMF1 regulates autophagy and ion channels' function in renal cell carcinoma: a future therapeutic target.

INTRODUCTION: In RCC, systematic procedures such as surgery, chemo-radiation therapy, and application of target-based inhibitors increase the risk of several comorbidities such as chronic kidney disease, hemorrhage, and cardiac arrest that may increase the mortality rate. Even though immune-based checkpoint inhibitor therapies have an overall good response rate, it is restricted to only 30-40% of patients. Hence, an in-depth study of tumor pathophysiology in RCC is needed to identify the new therapeutic target. In RCC, persisted hypoxia is an essential phenomenon for tumor growth and progression. KCMF1 is a newly identified ubiquitin ligase whose domain interacts with destabilized proteins and reprogrammed the ubiquitin coding for lysosome-mediated degradation and autophagy under hypoxic conditions/oxidative stress and maintaining cellular homeostasis. But in RCC, the functional role of KCMF1 remains undefined to date. METHOD: We determined KCMF1 and its associated proteins RAD6 and UBR4 expression and their co-localization using confocal microscopy in tumor and non-tumor tissues samples. Further, immunofluorescence staining was performed to determine autophagy (LC3B, p62), hypoxia-inducible factor (HIF-1A) and ion channel markers (Kv1.3, KCNN4) in RCC patients (n-10). Inductively coupled plasma mass spectrophotometry (ICPMS) was performed to estimate the concentration of potassium (K+), sodium (Na+) and Zinc (zn2+) in tumor and non-tumor cells of RCC patients (n-20). Lastly, images were analyzed using ZEN3.1, and ImageJ software. RESULT AND CONCLUSION: We observed a discrepancy in the formation of ubiquitin ligase, autophagosome via KCMF1, and ionic concentration in tumor cells, which might be one of the possible factors for cancer evolution. KCMF1-associated ubiquitin ligase system could be considered as a novel therapeutic target for RCC in the future.