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Objective: To evaluate the cardioprotective effect of bioassay-guided isolated fractions of Cleome viscosa methanolic extract in streptozotocin-induced diabetic rats. Methods: Total phenolics, flavonoids, and in vitro antioxidant activities of the methanolic extract of Cleome viscosa were evaluated. The FD-40 fraction from this extract was further evaluated for antihyperglycemic efficacy (insulin and HbA1c), antioxidant activity, and cardioprotective effects (creatine kinase-MB, lactate dehydrogenase, and histopathology) in streptozotocin-induced diabetic rats. In silico studies were also conducted to assess the bioactivity of FD-40. Results: Cleome viscosa methanolic extract exhibited the highest antioxidant activity in DPPH, ABTS, H2O2, and FRAP assays compared to other extracts. Treatment with FD-40 (40 mg/kg b.w.) isolated from this extract normalized blood glucose, insulin, HbA1c, creatine kinase-MB, and lactate dehydrogenase levels in diabetic rats. It also significantly reduced oxidative stress by increasing antioxidant enzymes, decreasing lipid peroxidation as well as restoring the levels of ascorbic acid and glutathione. Histological study demonstrated that FD-40 treatment improved cardiac structure in diabetic rats. Molecular docking analysis revealed that phytocompounds from FD-40 had strong binding affinities with cardiac markers and oxidative enzymes. Hexose (5TMS) demonstrated greater binding affinity with xanthine oxidase and lactate dehydrogenase. Conclusions: FD-40 of Cleome viscosa methanolic extract exhibits significant cardioprotective effects in diabetic rats by regulating cardiac markers and reducing oxidative stress. The underlying mechanisms need to be elucidated in the future.

In India, it is not uncommon for individuals to attempt suicide by ingesting pesticides. Though several publications have reported cases, there are no specific guidelines for managing indoxacarb poisoning. There is no established antidote for indoxacarb poisoning; however, early recognition and treatment of methemoglobinaemia, the primary manifestation, is essential. Early intervention is crucial for a positive outcome. Methemoglobinaemia can be successfully treated with methylene blue, which serves as the first line of management. This case report describes a 24-year-old man presenting with methemoglobinaemia following the ingestion of indoxacarb combined with novaluron and was successfully treated with early administration of methylene blue, leading to rapid recovery despite a methaemoglobin level as high as 75%.

PURPOSEThe information on the practice of radiotherapy, including intensity-modulated radiotherapy (IMRT) use for rectal cancer in India, is lacking. This national survey was planned to understand the current status of knowledge, attitudes, and practice among radiation oncologists, specifically concerning the practice of IMRT for rectal cancers.MATERIALS AND METHODSA national survey was sent to radiation oncologists through e-mail or a WhatsApp message, where feasible, with a request letter containing the link to the survey questionnaire. The survey questionnaire was adapted from the UK IMRT survey with permission from the authors. It explored rectal cancer management, IMRT use, reasons for nonadoption, total neoadjuvant therapy (TNT), dose fractionation schedules and radiotherapy processes like radiotherapy simulation, target volume/organ at risk definition, and treatment planning, evaluation, and verification. Descriptive statistics is used to present the results.RESULTSOver 300 radiation oncologists were approached, and 182 (60.6%) of the 153 institutes responded. Around 88% (160 of 182) indicated using IMRT or volumetric modulated arc therapy (VMAT) to treat rectal cancer, of whom 32% used exclusively IMRT/VMAT in all their patients. The reasons for not adopting IMRT were affordability/lack of insurance, resource constraints, and lack of guidelines. Long-course chemoradiation (capecitabine-based) followed by surgery was the most common neoadjuvant approach, with short course and TNT in less than a third of patients. Daily verification feasibility was reported by 60%. Seventy-three percent emphasized the need for a national IMRT guidance document.CONCLUSIONThis national survey from India indicates a scope of routine implementation of IMRT in rectal cancer, highlighting the urgent need for a national IMRT guidance document, which could significantly enhance the quality of care for patients with rectal cancer in India.

Mitochondria play a significant and varied role in inflammatory lung disorders. Mitochondria, known as the powerhouse of the cell because of their role in producing energy, are now recognized as crucial regulators of inflammation and immunological responses. Asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome are characterized by complex interactions between immune cells, inflammatory substances, and tissue damage. Dysfunctional mitochondria can increase the generation of reactive oxygen species (ROS), triggering inflammatory pathways. Moreover, mitochondrial failure impacts cellular signaling, which in turn affects the expression of molecules that promote inflammation. In addition, mitochondria have a crucial role in controlling the behavior of immune cells, such as their activation and differentiation, which is essential in the development of inflammatory lung diseases. Their dynamic behavior, encompassing fusion, fission, and mitophagy, also impacts cellular responses to inflammation and oxidative stress. Gaining a comprehensive understanding of the intricate correlation between mitochondria and lung inflammation is essential in order to develop accurate treatment strategies. Targeting ROS generation, dynamics, and mitochondrial function may offer novel approaches to treating inflammatory lung diseases while minimizing tissue damage. Additional investigation into the precise contributions of mitochondria to lung inflammation will provide significant knowledge regarding disease mechanisms and potential therapeutic approaches. This review will focus on how mitochondria in the lung regulate these processes and their involvement in acute and chronic lung diseases.

Various applications use asymmetric cryptography to secure communications between both parties, and it raises the main issue of generating vast amounts of computation and storage. Thus, elliptic curve cryptography (ECC) is a methodology that emerged to overcome this issue using its low computation and generation of small keys with its strong encryption strategy. ECC is becoming mandatory and used mostly for public key encryption protocols. ECC has expanded cumulative acceptance in practice due to the reduced bit magnitude of operands compared to RSA for safety level. Previously, protocols designed for ECC suggested calculation of scalar development and it was accomplished in finite fields as projective, affine, and Jacobian simulations of coordinates. Arithmetic operations in a limited area establish the core benefits of the ECC algorithm. Even though ECC generated an issue of complex key generation using its curve formation, to overcome this issue a hyperelliptic curve cryptosystems (HECC) is proposed in this study. HECC perform ECC in the Public Key Cryptography (PKC) domain. This study presented an optimization-based key generation and made a random selection of integers for encrypting the message. Selecting a prime number as the private key and multiplying it to the encrypted message to generate a public key is done. This encrypted message is mapped to the curve to check whether it satisfies the curve equation or not. Once an encrypted message is obtained, it is then sent to a second party for pursuing the message. On the side of the second party, a reverse process called decryption takes place. Thus, a secured transmission of data communication takes place. Implementing this algorithm in MATLAB resulted in 94% accuracy and an error of 6%, which was a higher performance ratio than previous methods.

Liver cancer represents a substantial global health challenge, contributing significantly to worldwide morbidity and mortality. It has long been understood that tumors are not composed solely of cancerous cells, but also include a variety of normal cells within their structure. These tumor-associated normal cells encompass vascular endothelial cells, fibroblasts, and various inflammatory cells, including neutrophils, monocytes, macrophages, mast cells, eosinophils, and lymphocytes. Additionally, tumor cells engage in complex interactions with stromal cells and elements of the extracellular matrix (ECM). Initially, the components of what is now known as the tumor microenvironment (TME) were thought to be passive bystanders in the processes of tumor proliferation and local invasion. However, recent research has significantly advanced our understanding of the TME’s active role in tumor growth and metastasis. Tumor progression is now known to be driven by an intricate imbalance of positive and negative regulatory signals, primarily influenced by specific growth factors produced by both inflammatory and neoplastic cells. This review article explores the latest developments and future directions in understanding how the TME modulates liver cancer, with the aim of informing the design of novel therapies that target critical components of the TME.

Abstract Background Reproductive stage drought stress (RDS) is a major global threat to rice production. Due to climate change, water scarcity is becoming an increasingly common phenomenon in major rice-growing areas worldwide. Understanding RDS mechanisms will allow candidate gene identification to generate novel rice genotypes tolerant to RDS. Results To generate novel rice genotypes that can sustain yield under RDS, we performed gamma-irradiation mediated mutation breeding in the drought stress susceptible mega rice variety, MTU1010. One of the mutant MM11 (MTU1010 derived mutant11) shows consistently increased performance in yield-related traits under field conditions consecutively for four generations. In addition, compared to MTU1010, the yield of MM11 is sustained in prolonged drought imposed during the reproductive stage under field and in pot culture conditions. A comparative emerged panicle transcriptome analysis of the MTU1010 and MM11 suggested metabolic adjustment, enhanced photosynthetic ability, and hormone interplay in regulating yield under drought responses during emerged panicle development. Regulatory network analysis revealed few putative significant transcription factor (TF)-target interactions involved in integrated signalling between panicle development, yield and drought stress. Conclusions A gamma-irradiate rice mutant MM11 was identified by mutation breeding, and it showed higher potential to sustain yield under reproductive stage drought stress in field and pot culture conditions. Further, a comparative panicle transcriptome revealed significant biological processes and molecular regulators involved in emerged panicle development, yield and drought stress integration. The study extends our understanding of the physiological mechanisms and candidate genes involved in sustaining yield under drought stress.

This paper deals with the evolution of downlink codebook based multiple-input multiple-output (MIMO) within the third generation partnership project (3GPP) through release 15 to 17. There exist already several tutorials on this topic. However, to the authors’ knowledge, the comparison in terms of complexity performance trade-off between practical precoder selection strategies in frequency or delay domain has not been tackled so far in the literature. This paper describes with matrix formalism the two main codebook types specified within 3GPP, i.e., Type-I codebook (low resolution) and Type-II codebook (high resolution). The Rel. 17 port selection is also detailed as well as the multi-user MIMO (MU-MIMO) precoding strategy to be applied relying on Type-II codebook feedback. For the enhanced Type-II codebook, two main practical precoder selection strategies are detailed at the UE side (i) based on singular value decomposition per sub-band in the frequency domain, (ii) based on wideband singular decomposition in the delay domain. Monte Carlo simulations demonstrate that the delay domain strategy performance may suffer from spatial interference for single user MIMO high rank transmissions when the channel is both spatially correlated and frequency selective. On the other hand, the frequency domain strategy complexity increases linearly with the number of sub-bands while it is not the case for the delay domain selection strategy. As a result, the delay domain selection strategy is particularly relevant for Rel. 17 Type-II codebook port selection or for a low frequency selective channel with few significant consecutive delays.

Embryo rescue is a vital technique in cucurbit breeding and propagation, addressing challenges such as embryo abortion, poor seed viability, and incompatibility barriers. This method involves the excision of immature embryos from seeds followed by their in vitro culture on a nutrient medium, providing an environment conducive to their growth and development. In cucurbits, embryo rescue has been extensively utilized to overcome barriers to hybridization, enabling the production of interspecific and intergeneric hybrids with desired traits. Various factors, including genotype, developmental stage of embryos, and culture conditions, influence the success of embryo rescue in cucurbits. Optimal nutrient formulations, growth regulators, and culture techniques are critical for promoting embryo germination, shoot elongation, and subsequent plantlet establishment. Additionally, embryo rescue facilitates the recovery of valuable genetic material from wild and exotic cucurbit species, expanding genetic diversity and developing novel cultivars with improved traits such as disease resistance, yield, and quality. This review highlights the principles, applications, and advancements in embryo rescue technology in cucurbits, emphasizing its significance in cucurbit breeding programs and crop improvement efforts.

Arrhythmias have been reported frequently in COVID-19 patients, but the incidence and nature have not been well characterized. Patients admitted with COVID-19 and monitored by telemetry were prospectively enrolled in the study. Baseline characteristics, hospital course, treatment and complications were collected from the patients' medical records. Telemetry was monitored to detect the incidence of cardiac arrhythmias. The incidence and types of cardiac arrhythmias were analyzed and compared between survivors and non-survivors. Among 143 patients admitted with telemetry monitoring, overall in-hospital mortality was 25.2% (36/143 patients) during the period of observation (mean follow-up 23.7 days). Survivors were less tachycardic on initial presentation (heart rate 90.6 ± 19.6 vs. 99.3 ± 23.1 bpm, p = 0.030) and had lower troponin (peak troponin 0.03 vs. 0.18 ng/ml. p = 0.004), C-reactive protein (peak C-reactive protein 97 vs. 181 mg/dl, p = 0.029), and interleukin-6 levels (peak interleukin-6 30 vs. 246 pg/ml, p = 0.003). Sinus tachycardia, the most common arrhythmia (detected in 39.9% [57/143] of patients), occurred more frequently in non-survivors (58.3% vs. 33.6% in survivors, p = 0.009). Premature ventricular complexes occurred in 28.7% (41/143), and non-sustained ventricular tachycardia in 15.4% (22/143) of patients, with no difference between survivors and non-survivors. Sustained ventricular tachycardia and ventricular fibrillation were not frequent (seen only in 1.4% and 0.7% of patients, respectively). Contrary to reports from other regions, overall mortality was higher and ventricular arrhythmias were infrequent in this hospitalized and monitored COVID-19 population. Either disease or management-related factors could explain this divergence of clinical outcomes, and should be urgently investigated.

Saturation flow rate is the prime important parameter for the design of capacity of signal-controlled intersections. The width of the approach is one of the most important factors for the evaluation of saturation flow. But, in countries like India, due to the increase in commercial and social land usage, especially on roadsides, there are many factors that affect road width performance, among which side friction is one of the most important factors. In the present research study, an attempt is made to find the impact of side friction on saturation flow at signalized intersections in mixed traffic conditions. For this purpose, the data was collected from four different cities: Hyderabad, Hanmakonda, Raipur and Calicut. A multiple linear regression model is developed for estimating saturation flow in the present study. In addition to the saturation flow model, the present work provides adjustment factors for side friction to calculate saturation flow.

Background/Aims: Current society guidelines recommend antibiotic prophylaxis for 3 to 5 days after endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions (PCLs). The overall quality of the evidence supporting this recommendation is low. In this study, we aimed to assess cyst infection and adverse event rates after EUS-FNA of PCLs among patients treated with or without postprocedural prophylactic antibiotics. Methods: We retrospectively reviewed all patients who underwent EUS-FNA of PCLs between 2015 and 2019 at two large-volume academic medical centers with different practice patterns of postprocedural antibiotic prophylaxis. Data on patient demographics, cyst characteristics, fine-needle aspiration technique, periprocedural and postprocedural antibiotic prophylaxis, and adverse events were retrospectively extracted. Results: A total of 470 EUS-FNA procedures were performed by experienced endosonographers for the evaluation of PCLs in 448 patients, 58.7% of whom were women. The mean age was 66.3±12.8 years. The mean cyst size was 25.7±16.9 mm. Postprocedural antibiotics were administered in 274 cases (POSTAB+ group, 58.3%) but not in 196 cases (POSTAB– group, 41.7%). None of the patients in either group developed systemic or localized infection within the 30-day follow-up period. Procedure-related adverse events included mild abdominal pain (8 patients), intra-abdominal hematoma (1 patient), mild pancreatitis (1 patient), and perforation (1 patient). One additional case of pancreatitis was recorded; however, the patient also underwent endoscopic retrograde cholangiopancreatography. Conclusions: The incidence of infection after EUS-FNA of PCLs is negligible. Routine use of postprocedural antibiotics does not add a significant benefit.

Abstract Background The administration of 5-fluorouracil (5FU) in the treatment of gastrointestinal (GI) malignancies is associated with common side effects such as mucositis, diarrhoea, and myelosuppression, which are easily managed with supportive measures and dose adjustments. Cardiotoxicity and neurotoxicity are rare but reversible side effects of 5-FU and are treated with withdrawal of the drug and conservative measures. The presenting symptoms of 5-FU-induced leukoencephalopathy are often confusing and pose a diagnostic dilemma in routine clinical practice. Methods We report a series of five patients with GI malignancies who developed 5-FU-induced leukoencephalopathy. Results All (n = 5) had Naranjo scores of 6–7, predictive of 5-FU-related adverse effects, with clinical and radiological findings suggestive of 5-FU-induced encephalopathy as described in prior literature. The median time to onset of symptoms from initiation of 5FU was 3 days (range: 2–4 days). All patients improved after conservative management with complete neurological recovery. Conclusion Prompt recognition of this rare yet severe adverse effect of 5-FU-based chemotherapy aids early withdrawal of the offending agent (5-FU) and timely initiation of supportive measures and helps plan alternative oncological interventions.

In the past decades, advances in the use of adoptive cellular therapy to treat cancer have led to unprecedented responses in patients with relapsed/refractory or late-stage malignancies. However, cellular exhaustion and senescence limit the efficacy of FDA-approved T-cell therapies in patients with hematologic malignancies and the widespread application of this approach in treating patients with solid tumors. Investigators are addressing the current obstacles by focusing on the manufacturing process of effector T cells, including engineering approaches and ex vivo expansion strategies to regulate T-cell differentiation. Here we reviewed the current small-molecule strategies to enhance T-cell expansion, persistence, and functionality during ex vivo manufacturing. We further discussed the synergistic benefits of the dual-targeting approaches and proposed novel vasoactive intestinal peptide receptor antagonists (VIPR-ANT) peptides as emerging candidates to enhance cell-based immunotherapy.

Introduction: Nursing fraternity plays a pivotal role in psychiatric services. Psychiatric conditions and persons suffering from them may elicit the different kinds of attitudinal responses. While there are multiple factors leading to an individual's decision to specialize in psychiatry, the individual's perceptions and attitudes toward psychiatry tend to play an essential role Aim: The current study aimed at assessing the attitude toward psychiatry among nursing students at a tertiary care hospital. Design: Cross-sectional study. Materials and Methods: One hundred and thirty-seven nursing students from Tertiary care teaching hospital were recruited the study and administered attitudes assessed using Attitudes toward Psychiatry-18 Scale. Statistical Analysis: Data were analyzed using the SPSS statistics version 23. Results: Majority of respondents showed favorable attitudes toward 14 items and unfavorable attitudes in remaining 4 items. Only 29.9% participants expressed their willingness to specialize in psychiatric nursing. Conclusions: A study found majority of students having favorable attitudes toward psychiatry. More can be done in the present education and training curriculum to develop empathetic attitudes toward people with mental illness, as it will affect the way these prospective nursing students deliver care toward their patients.

BackgroundThe American Society of Gastrointestinal Endoscopy (ASGE) has proposed practice guidelines for evaluating patients with suspected choledocholithiasis. This study aims to assess and compare practice patterns for following ASGE guidelines for choledocholithiasis in a large academic vs. community hospital setting.MethodsA total of one thousand ER indicated for choledocholithiasis were randomly selected. Patients’ demographics, total bilirubin, imaging studies including magnetic resonance cholangiopancreatography (MRCP), intraoperative cholangiogram (IOC), endoscopic ultrasound (EUS), and ERCP results were retrospectively collected. Patients with prior sphincterotomy were excluded. We examined the following practice deviations from the current ASGE guidelines; (1) ERCP was potentially delayed in high probability cases while awaiting additional imaging studies, (2) ERCP was performed without additional imaging studies in cases of low/intermediate-risk, or (3) ERCP was performed in low/intermediate-risk cases when additional imaging studies were negative.ResultsA total of 640 patients with native papilla who underwent ERCP were included in the final analysis. Overall, the management of 43% (275) of patients was deviated from the applicable ASGE guidelines. Academic and community provider rates of non-adherence were 32 vs. 45%, respectively (p-value: < 0.01). Of 381 high-risk cases, 54.1% had additional imaging before ERCP. (Academic vs. community; 11.7 vs. 88.3%, p-value: < 0.01). In 26.7% (69/258) of low/intermediate risk cases, ERCP was performed without additional studies; academic (14.5%) vs. community (85.5%) (p-value: < 0.01). Finally, in 11.2% (19/170) of patients, ERCP was performed despite intermediate/low probability and negative imaging; academic (26.3%) vs. community (73.7%) (p-value: 0.02).ConclusionOur study results show that providers do not adhere to ASGE practice guidelines in 43% of suspected choledocholithiasis cases. The rate of non-adherence was significantly higher in community settings. It could be due to various reasons, including lack/delays for alternate studies (i.e., MRCP, EUS), concern regarding the length of stay, patient preference, or lack of awareness/understanding of the guidelines. Increased availability of alternate imaging and educational strategies may be needed to increase the adoption of practice guidelines across academic and community settings to improve patient outcomes and save healthcare dollars.

Background: Critically ill patients on supplemental oxygen therapy eventually develop acute lung injury (ALI). Reactive oxygen species (ROS) produced during ALI perturbs the mitochondrial dynamics resulting in cellular damage. Genetic deletion of the mitochondrial A-kinase anchoring protein 1 (Akap1) in mice resulted in mitochondrial damage, Endoplasmic reticulum (ER) stress, increased expression of mitophagy proteins and pro-inflammatory cytokines, exacerbating hyperoxia-induced Acute Lung Injury (HALI).Objective: Despite a strong causal link between mitochondrial dysfunction and HALI, the mechanisms governing the disease progression at the transcriptome level is unknown.Methods: In this study, RNA sequencing (RNA-seq) analysis was carried out using the lungs of Akap1 knockout (Akap1−/−) mice exposed to normoxia or 48 h of hyperoxia followed by quantitative real time PCR and Ingenuity pathway analysis (IPA). Western blot analysis assessed mitochondrial dysfunction, OXPHOS complex (I-V), apoptosis and antioxidant proteins. Mitochondrial enzymatic assays was used to measure the aconitase, fumarase, citrate synthase activities in isolated mitochondria from Akap1−/− vs. Wt mice exposed to hyperoxia.Results: Transcriptome analysis of Akap1−/− exposed to hyperoxia reveals increases in transcripts encoding electron transport chain (ETC) and tricarboxylic acid cycle (TCA) proteins. Ingenuity pathway analysis (IPA) shows enrichment of mitochondrial dysfunction and oxidative phosphorylation in Akap1−/− mice. Loss of AKAP1, coupled with oxidant injury, significantly decreases the activities of TCA enzymes. Mechanistically, a significant loss of dynamin-related protein 1 (Drp1) phosphorylation at the protein kinase A (PKA) site Serine 637 (Ser637), decreases in Akt phosphorylation at Serine 437 (Ser47) and increase in the expression of pro-apoptotic protein Bax indicate mitochondrial dysfunction. Heme oxygenase-1 (HO-1) levels significantly increased in CD68 positive alveolar macrophages in Akap1−/− lungs, suggesting a strong antioxidant response to hyperoxia.Conclusion: Overall these results suggest that AKAP1 overexpression and modulation of Drp1 phosphorylation at Ser637 is an important therapeutic strategy for acute lung injury.

Objective: To evaluate the cardioprotective effect of bioassay-guided isolated fractions of Cleome viscosa methanolic extract in streptozotocin-induced diabetic rats. Methods: Total phenolics, flavonoids, and in vitro antioxidant activities of the methanolic extract of Cleome viscosa were evaluated. The FD-40 fraction from this extract was further evaluated for antihyperglycemic efficacy (insulin and HbA1c), antioxidant activity, and cardioprotective effects (creatine kinase-MB, lactate dehydrogenase, and histopathology) in streptozotocin-induced diabetic rats. In silico studies were also conducted to assess the bioactivity of FD-40. Results: Cleome viscosa methanolic extract exhibited the highest antioxidant activity in DPPH, ABTS, H2O2, and FRAP assays compared to other extracts. Treatment with FD-40 (40 mg/kg b.w.) isolated from this extract normalized blood glucose, insulin, HbA1c, creatine kinase-MB, and lactate dehydrogenase levels in diabetic rats. It also significantly reduced oxidative stress by increasing antioxidant enzymes, decreasing lipid peroxidation as well as restoring the levels of ascorbic acid and glutathione. Histological study demonstrated that FD-40 treatment improved cardiac structure in diabetic rats. Molecular docking analysis revealed that phytocompounds from FD-40 had strong binding affinities with cardiac markers and oxidative enzymes. Hexose (5TMS) demonstrated greater binding affinity with xanthine oxidase and lactate dehydrogenase. Conclusions: FD-40 of Cleome viscosa methanolic extract exhibits significant cardioprotective effects in diabetic rats by regulating cardiac markers and reducing oxidative stress. The underlying mechanisms need to be elucidated in the future. [ABSTRACT FROM AUTHOR]

Rapidly identifying candidate genes underlying major QTLs is crucial for improving rice (Oryza sativa L.). In this study, we developed a workflow to rapidly prioritize candidate genes underpinning 99 major QTLs governing yield component traits. This workflow integrates multiomics databases, including sequence variation, gene expression, gene ontology, co-expression analysis, and protein–protein interaction. We predicted 206 candidate genes for 99 reported QTLs governing ten economically important yield-contributing traits using this approach. Among these, transcription factors belonging to families of MADS-box, WRKY, helix–loop–helix, TCP, MYB, GRAS, auxin response factor, and nuclear transcription factor Y subunit were promising. Validation of key prioritized candidate genes in contrasting rice genotypes for sequence variation and differential expression identified Leucine-Rich Repeat family protein (LOC_Os03g28270) and cytochrome P450 (LOC_Os02g57290) as candidate genes for the major QTLs GL1 and pl2.1 , which govern grain length and panicle length, respectively. In conclusion, this study demonstrates that our workflow can significantly narrow down a large number of annotated genes in a QTL to a very small number of the most probable candidates, achieving approximately a 21-fold reduction. These candidate genes have potential implications for enhancing rice yield. [ABSTRACT FROM AUTHOR]

Liver cancer represents a substantial global health challenge, contributing significantly to worldwide morbidity and mortality. It has long been understood that tumors are not composed solely of cancerous cells, but also include a variety of normal cells within their structure. These tumor-associated normal cells encompass vascular endothelial cells, fibroblasts, and various inflammatory cells, including neutrophils, monocytes, macrophages, mast cells, eosinophils, and lymphocytes. Additionally, tumor cells engage in complex interactions with stromal cells and elements of the extracellular matrix (ECM). Initially, the components of what is now known as the tumor microenvironment (TME) were thought to be passive bystanders in the processes of tumor proliferation and local invasion. However, recent research has significantly advanced our understanding of the TME's active role in tumor growth and metastasis. Tumor progression is now known to be driven by an intricate imbalance of positive and negative regulatory signals, primarily influenced by specific growth factors produced by both inflammatory and neoplastic cells. This review article explores the latest developments and future directions in understanding how the TME modulates liver cancer, with the aim of informing the design of novel therapies that target critical components of the TME. [ABSTRACT FROM AUTHOR]

Mitochondria play a significant and varied role in inflammatory lung disorders. Mitochondria, known as the powerhouse of the cell because of their role in producing energy, are now recognized as crucial regulators of inflammation and immunological responses. Asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome are characterized by complex interactions between immune cells, inflammatory substances, and tissue damage. Dysfunctional mitochondria can increase the generation of reactive oxygen species (ROS), triggering inflammatory pathways. Moreover, mitochondrial failure impacts cellular signaling, which in turn affects the expression of molecules that promote inflammation. In addition, mitochondria have a crucial role in controlling the behavior of immune cells, such as their activation and differentiation, which is essential in the development of inflammatory lung diseases. Their dynamic behavior, encompassing fusion, fission, and mitophagy, also impacts cellular responses to inflammation and oxidative stress. Gaining a comprehensive understanding of the intricate correlation between mitochondria and lung inflammation is essential in order to develop accurate treatment strategies. Targeting ROS generation, dynamics, and mitochondrial function may offer novel approaches to treating inflammatory lung diseases while minimizing tissue damage. Additional investigation into the precise contributions of mitochondria to lung inflammation will provide significant knowledge regarding disease mechanisms and potential therapeutic approaches. This review will focus on how mitochondria in the lung regulate these processes and their involvement in acute and chronic lung diseases. [ABSTRACT FROM AUTHOR]

Rationale: Idiopathic pulmonary fibrosis (IPF) is characterized by mitochondrial dysfunction. However, details about the non-mitochondrial enzymes that sustain the proliferative nature of IPF are unclear. Aconitases are a family of enzymes that sustain metabolism inside and outside mitochondria. It is hypothesized that aconitase 1 (ACO1) plays an important role in the pathogenesis of IPF given that ACO1 represents an important metabolic hub in the cytoplasm.Objectives: To determine if ACO1 expression in IPF lungs shows specific patterns that may be important in the pathogenesis of IPF. To determine the similarities and differences in ACO1 expression in IPF, bleomycin-treated, and aging lungs.Methods: ACO1 expression in IPF lungs were characterized and compared to non-IPF controls by western blotting, immunostaining, and enzymatic activity assay. ACO1-expressing cell types were identified by multicolor immunostaining. Using similar methods, the expression profiles of ACO1 in IPF lungs versus bleomycin-treated and aged mice were investigated.Measurements and main results: Lower lobes of IPF lungs, unlike non-IPF controls, exhibit significantly high levels of ACO1. Most of the signals colocalize with von Willebrand factor (vWF), a lineage marker for vascular endothelial cells. Bleomycin-treated lungs also show high ACO1 expressions. However, most of the signals colocalize with E-cadherin and/or prosurfactant protein C, representative epithelial cell markers, in remodeled areas.Conclusions: A characteristic ACO1 expression profile observed in IPF vasculatures may be a promising diagnostic target. It also may give clues as to how de novo angiogenesis contributes to the irreversible nature of IPF.

Abstract Dual‐graphite batteries (DGBs), being an all‐graphite‐electrode variation of dual‐ion batteries (DIBs), have attracted great attention in recent years as a possible low‐cost technology for stationary energy storage due to the utilization of inexpensive graphite as a positive electrode (cathode) material. However, DGBs suffer from a low specific energy limited by the capacity of both electrode materials. In this work, a composite of black phosphorus with carbon (BP‐C) is introduced as negative electrode (anode) material for DIB full‐cells for the first time. The electrochemical behavior of the graphite || BP‐C DIB cells is then discussed in the context of DGBs and DIBs using alloying anodes. Mechanistic studies confirm the staging behavior for anion storage in the graphite positive electrode and the formation of lithiated phosphorus alloys in the negative electrode. BP‐C containing full‐cells demonstrate promising electrochemical performance with specific energies of up to 319 Wh kg–1 (related to masses of both electrode active materials) or 155 Wh kg–1 (related to masses of electrode active materials and active salt), and high Coulombic efficiency. This work provides highly relevant insights for the development of advanced high‐energy and safe DIBs incorporating BP‐C and other high‐capacity alloying materials in their anodes.

Context: Multimorbidity (MM) is a global concern following the increase in life expectancy, the conquering of major infectious diseases, and the advances in the management of chronic illnesses. It places a substantial burden on patients and healthcare systems. Aims: This study aims to describe the prevalence and pattern of MM in adults among primary healthcare users in Qatar. Settings and Design: A retrospective cross-sectional study design. Methods and Material: Data were extracted from the electronic health records of patients aged 18 years and above who registered for care with 27 primary health centres in Qatar from 1st January 2017 to 30th June 2020. The distribution of MM among age groups, gender and nationality was analysed. Results: In the study population of 7,96,427, the prevalence of MM was found to be 22.1%. MM was more prevalent in females (51.2%) than males (48.8%). The prevalence of MM showed an increasing trend with increasing age, with a peak of 25.8% found in the 46–55 age group. Qatari nationals accounted for 32.7% of MM, Southeast Asians for 28.3%, North Africans for 16.7% and individuals from other Middle Eastern countries for 14.1%. The five most common long-term chronic conditions were type-2 diabetes mellitus, hypertension, dyslipidaemia, obesity and eczema, with the first three being the most prevalent disease clusters. Conclusions: Our findings confirm that MM is common in Qatar's primary care centres. While the prevalence of MM was found to increase with increasing age, the largest proportion of patients with MM were those aged 46–55 years. This information adds to the available data on MM and directs health policymakers towards tailoring the management for the same.

Triple-negative breast cancer (TNBC) afflicts women at a younger age than other breast cancers and is associated with a worse clinical outcome. This poor clinical outcome is attributed to a lack of defined targets and patient-to-patient heterogeneity in target antigens and immune responses. To address such heterogeneity, we tested the efficacy of a personalized vaccination approach for the treatment of TNBC using the 4T1 murine TNBC model. We isolated tumor membrane vesicles (TMVs) from homogenized 4T1 tumor tissue and incorporated glycosyl phosphatidylinositol (GPI)-anchored forms of the immunostimulatory B7-1 (CD80) and IL-12 molecules onto these TMVs to make a TMV vaccine. Tumor-bearing mice were then administered with the TMV vaccine either alone or in combination with immune checkpoint inhibitors. We show that TMV-based vaccine immunotherapy in combination with anti-CTLA-4 mAb treatment upregulated immunomodulatory cytokines in the plasma, significantly improved survival, and reduced pulmonary metastasis in mice compared to either therapy alone. The depletion of CD8+ T cells, but not CD4+ T cells, resulted in the loss of efficacy. This suggests that the vaccine acts via tumor-specific CD8+ T cell immunity. These results suggest TMV vaccine immunotherapy as a potential enhancer of immune checkpoint inhibitor therapies for metastatic triple-negative breast cancer.

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are treated with high concentrations of supplementary oxygen. However, prolonged exposure to high oxygen concentrations stimulates the production of reactive oxygen species (ROS), which damages the mitochondria and accumulates misfolded proteins in the endoplasmic reticulum (ER). The mitochondrial protein A-kinase anchoring protein 1 (Akap1) is critical for mitochondrial homeostasis. It is known that Akap1 deficiency results in heart damage, neuronal development impairment, and mitochondrial malfunction in preclinical studies. Our laboratory recently revealed that deleting Akap1 increases the severity of hyperoxia-induced ALI in mice. To assess the role of Akap1 deletion in ER stress in lung injury, wild-type and Akap1−/− mice were exposed to hyperoxia for 48 h. This study indicates that Akap1−/− mice exposed to hyperoxia undergo ER stress, which is associated with an increased expression of BiP, JNK phosphorylation, eIF2α phosphorylation, ER stress-induced cell death, and autophagy. This work demonstrates that deleting Akap1 results in increased ER stress in the lungs of mice and that hyperoxia exacerbates ER stress-related consequences.

Sedentary plant-parasitic cyst nematodes are biotrophs that cause significant losses in agriculture. Parasitism is based on modifications of host root cells that lead to the formation of a hypermetabolic feeding site (a syncytium) from which nematodes withdraw nutrients. The host cell cycle is activated in an initial cell selected by the nematode for feeding, followed by activation of neighboring cells and subsequent expansion of feeding site through fusion of hundreds of cells. It is generally assumed that nematodes manipulate production and signaling of the plant hormone cytokinin to activate cell division. In fact, nematodes have been shown to produce cytokinin in vitro; however, whether the hormone is secreted into host plants and plays a role in parasitism remained unknown. Here, we analyzed the spatiotemporal activation of cytokinin signaling during interaction between the cyst nematode, Heterodera schachtii, and Arabidopsis using cytokinin-responsive promoter:reporter lines. Our results showed that cytokinin signaling is activated not only in the syncytium but also in neighboring cells to be incorporated into syncytium. An analysis of nematode infection on mutants that are deficient in cytokinin or cytokinin signaling revealed a significant decrease in susceptibility of these plants to nematodes. Further, we identified a cytokinin-synthesizing isopentenyltransferase gene in H. schachtii and show that silencing of this gene in nematodes leads to a significant decrease in virulence due to a reduced expansion of feeding sites. Our findings demonstrate the ability of a plant-parasitic nematode to synthesize a functional plant hormone to manipulate the host system and establish a long-term parasitic interaction.