Machine learning assisted designing of conjugated organic chromophores, light absorption, and emission behavior prediction.

Organic materials have several important characteristics that make them suitable for use in optoelectronics and optical signal processing applications. For absorption and emission maxima, the stabilities and photoactivities of conjugated organic chromophores can be tailored by selecting a suitable parent structure and incorporating substituents that predictably change the optical characteristics. However, a high-throughput design of efficient conjugated organic chromophores without using trial-and-error experimental approaches is required. In this study, machine learning (ML) is used to design and test the conjugated organic chromophores and predict light absorption and emission behavior. Many machine learning models are tried to select the best models for the prediction of absorption and emission maxima. Extreme gradient boosting regressor has appeared as the best model for the prediction of absorption maxima. Random forest regressor stands out as the best model for the prediction of emission maxima. Breaking Retrosynthetically Interesting Chemical Substructures (BRICS) is used to generate 10,000 organic chromophores. Chemical similarity analysis is performed to obtain a deeper understanding of the characteristics and actions of compounds. Furthermore, clustering and heatmap approaches are utilized.

Cellular Aging and Senescence in Cancer: A Holistic Review of Cellular Fate Determinants.

This comprehensive review navigates the complex relationship between cellular aging, senescence, and cancer, unraveling the determinants of cellular fate. Beginning with an overview of cellular aging's significance in cancer, the review explores processes, changes, and molecular pathways influencing senescence. The review explores senescence as a dual mechanism in cancer, acting as a suppressor and contributor, focusing on its impact on therapy response. This review highlights opportunities for cancer therapies that target cellular senescence. The review further examines the senescence-associated secretory phenotype and strategies to modulate cellular aging to influence tumor behavior. Additionally, the review highlights the mechanisms of senescence escape in aging and cancer cells, emphasizing their impact on cancer prognosis and resistance to therapy. The article addresses current advances, unexplored aspects, and future perspectives in understanding cellular aging and senescence in cancer.

Hallmarks of cancer resistance.

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

Targeting PI3K/AKT/mTOR signaling to overcome drug resistance in cancer.

This review comprehensively explores the challenge of drug resistance in cancer by focusing on the pivotal PI3K/AKT/mTOR pathway, elucidating its role in oncogenesis and resistance mechanisms across various cancer types. It meticulously examines the diverse mechanisms underlying resistance, including genetic mutations, feedback loops, and microenvironmental factors, while also discussing the associated resistance patterns. Evaluating current therapeutic strategies targeting this pathway, the article highlights the hurdles encountered in drug development and clinical trials. Innovative approaches to overcome resistance, such as combination therapies and precision medicine, are critically analyzed, alongside discussions on emerging therapies like immunotherapy and molecularly targeted agents. Overall, this comprehensive review not only sheds light on the complexities of resistance in cancer but also provides a roadmap for advancing cancer treatment.

Laboratory Evaluation of Indigenous and Commercial Entomopathogenic Nematodes against Red Palm Weevil, Rhynchophorus ferrugineus (Coleoptera: Curculionidae).

The red palm weevil (RPW) is a significant threat to date palms. Conventional pest control has been ineffective. This study aims to evaluate entomopathogenic nematodes (EPNs) indigenous to Saudi Arabia and commercial against RPW. We used 33 soil samples collected from four areas of Saudi Arabia. The indigenous EPNs were isolated and cultured using an insect baiting method to obtain infective juveniles. Pathogenicity bioassays were conducted against different stages of RPW, including eggs, larvae, and adults. The bioassay was performed using all the isolates at 1 × 106 IJ/mL. Distilled water was used as a control. The results revealed that only 9.09% of soil samples contained positive EPNs. Through DNA sequencing analysis, the positive samples were identified as indigenous isolates belonging to Heterorhabditis indica and Steinernema carpocapsae EPN species. In pathogenicity tests, 90% mortality of RPW eggs was observed after five days. Similar mortality trends were seen in RPW larvae and adults, with 90% mortality recorded after ten days for all the EPN treatments. Mortality increased with the duration of post-EPN inoculation exposure. The 1 × 106 IJ/mL concentrations of EPN effectively killed various stages of RPW in the laboratory. More research is needed to test EPNs against RPW in the field.

An effective tellurium surface modification strategy to enhance the capacity and rate capability of Ni-rich LiNi0.8Co0.1Mn0.1O2 cathode material.

LiNi0.8Co0.1Mn0.1O2 (NCM) layered oxide is contemplated as an auspicious cathode candidate for commercialized lithium-ion batteries. Regardless, the successful commercial utilization of these materials is impeded by technical issues like structural degradation and poor cyclability. Elemental doping is among the most viable strategies for enhancing electrochemical performance. Herein, the preparation of surface tellurium-doped NCM is done by utilizing the methodology solid-state route at high temperatures. Surface doping of the Te ions leads to structural stability owing to the inactivation of oxygen at the surface via the binding of slabs of transition metal-oxygen. Remarkably, 1 wt% of Te doping in NCM exhibits enhanced electrochemical characteristics with an excellent discharge capacity, i.e., 225.8 mAh/g (0.1C), improved rate-capability of 156 mAh/g (5C) with 82.2% retention in capacity (0.5C) over 100 cycles within 2.7-4.3V as compared to all other prepared electrodes. Hence, the optimal doping of Te is favorable for enhancing capacity, cyclability along with rate capability of NCM.

A Functional Air-Stable Li9.8GeP1.7Sb0.3S11.8I0.2 Superionic Conductor for High-Performance All-Solid-State Lithium Batteries.

Solid-state electrolytes (SSEs) based on sulfides have become a subject of great interest due to their superior Li-ion conductivity, low grain boundary resistance, and adequate mechanical strength. However, they grapple with chemical instability toward moisture hypersensitivity, which decreases their ionic conductivity, leading to more processing requirements. Herein, a Li9.8GeP1.7Sb0.3S11.8I0.2 (LGPSSI) superionic conductor is designed with a Li+ conductivity of 6.6 mS cm-1 and superior air stability based on hard and soft acids and bases (HSAB) theory. The introduction of optimal antimony (Sb) and iodine (I) into the Li10GeP2S12 (LGPS) structure facilitates fast Li-ion migration with low activation energy (Ea) of 20.33 kJ mol-1. The higher air stability of LGPSSI is credited to the strategic substitution of soft acid Sb into (Ge/P)S4 tetrahedral sites, examined by Raman and X-ray photoelectron spectroscopy techniques. Relatively lower acidity of Sb compared to phosphorus (P) realizes a stronger Sb-S bond, minimizing the evolution of toxic H2S (0.1728 cm3 g-1), which is ∼3 times lower than pristine LGPS when LGPSSI is exposed to moist air for 120 min. The NCA//Li-In full cell with a LGPSSI superionic conductor delivered the first discharge capacity of 209.1 mAh g-1 with 86.94% Coulombic efficiency at 0.1 mA cm-2. Furthermore, operating at a current density of 0.3 mA cm-2, LiNbO3@NCA/LGPSSI/Li-In cell demonstrated an exceptional reversible capacity of 117.70 mAh g-1, retaining 92.64% of its original capacity over 100 cycles.

Maggots cannot live on meat meal alone: production parameters for mass rearing of the ovoviviparous blowfly, Calliphora dubia (Diptera: Calliphoridae).

This study determined a cost-effective larval diet for rearing Calliphora dubia Macquart for use as a potential managed pollinator in Australia. This fly has potential as a pollination species to support honey bees (Apis mellifera). Larvae of C. dubia were reared mostly in meat meals with varying amounts of either whole egg powder, whole eggs (+ shell), bran flakes, skimmed milk powder, brewer's yeast, or poultry oil. This was done from an economic and production perspective to support commercial rearing. Several laboratory-based studies determined the growth and output from various ingredient combinations. Larvae fed 90% meat meal and 10% whole egg powder developed rapidly through to pupation with a high pupation rate, adult size, and percent adult emergence. Given the high cost and difficulty in sourcing whole egg powder, media comprising mostly meat meals with the addition of bran flakes and whole eggs also supported rapid larval development, pupation rate, and adult emergence. The ideal amount of media/larvae was 0.5 g/larvae to support high pupation rates and adult emergence. Adult eclosion occurred over 4-5 days, even when larvae were laid and fed within 1 h on ample media. Commercial mass rearing would then require daily cohorts of larvae to ensure peak adult fly emergence over 1-2 days for release into a crop. Mass-rearing C. dubia should use meat meal as the base ingredient with bran flakes and whole eggs added and fed at 0.5 g of media/larvae. Based on the current media ingredient costs, rearing 1-m adult C. dubia would cost just over $500 (US$342).

Osteomyelitis and non-coding RNAS: A new dimension in disease understanding.

Osteomyelitis, a debilitating bone infection, presents considerable clinical challenges due to its intricate etiology and limited treatment options. Despite strides in surgical and chemotherapeutic interventions, the treatment landscape for osteomyelitis remains unsatisfactory. Recent attention has focused on the role of non-coding RNAs (ncRNAs) in the pathogenesis and progression of osteomyelitis. This review consolidates current knowledge on the involvement of distinct classes of ncRNAs, including microRNAs, long ncRNAs, and circular RNAs, in the context of osteomyelitis. Emerging evidence from various studies underscores the potential of ncRNAs in orchestrating gene expression and influencing the differentiation of osteoblasts and osteoclasts, pivotal processes in bone formation. The review initiates by elucidating the regulatory functions of ncRNAs in fundamental cellular processes such as inflammation, immune response, and bone remodeling, pivotal in osteomyelitis pathology. It delves into the intricate network of interactions between ncRNAs and their target genes, illuminating how dysregulation contributes to the establishment and persistence of osteomyelitic infections. Understanding their regulatory roles may pave the way for targeted diagnostic tools and innovative therapeutic interventions, promising a paradigm shift in the clinical approach to this challenging condition. Additionally, we delve into the promising therapeutic applications of these molecules, envisioning novel diagnostic and treatment approaches to enhance the management of this challenging bone infection.

Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway.

Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice.

Dietary, addictive and habitual factors, and risk of colorectal cancer.

BACKGROUND: In Pakistan, the incidence of colorectal cancer (CRC) has sharply increased in recent years. Although several studies have reported global risk factors for CRC, no study has been conducted in Khyber Pakhtunkhwa (KPK), Pakistan, to investigate the risk factors associated with the increased CRC burden in this population. OBJECTIVES: Therefore, we conducted a clinical survey using a case-control study design to explore the risk factors associatd with CRC. METHODS: In the present study, one control was enrolled for each case. Both cases and controls were asked to complete a questionnaire to gather data. We analyzed all data using SPSS. RESULTS: Our study found that certain dietary factors, such as consuming fast food (OR: 3.0; P = 0.0001) and reusing ghee (OR: 2.45; P = 0.0001) and oil (OR: 4.30; P = 0.0001), increase the risk of CRC. Additionally, use of tobacco products like smoking cigarettes (OR: 1.91; P = 0.0001) and using snuff (OR: 3.72; P = 0.0001) significantly increases the risk of CRC. Certain habitual factors, including binge eating (OR: 2.42; P = 0.0001) and spending excessive time watching TV (OR: 1.98; P = 0.0001), also increase the odds of developing CRC. However, our study also identified some protective factors against CRC, such as consuming vegetables (OR: .41; P = 0.0001), developing healthy eating habits (OR: .61; P = 0.0001), and maintaining regular sleeping patterns (OR: .45; P = 0.0001). CONCLUSION: Given these findings, targeted health education is necessary to prevent the increase in CRC in this area. We also recommend developing and enforcing appropriate control guidelines for cancer risk factors to curb the incidence of CRC.

Chemistry Aspects and Designing Strategies of Flexible Materials for High-Performance Flexible Lithium-Ion Batteries.

In recent years, flexible and wearable electronics such as smart cards, smart fabrics, bio-sensors, soft robotics, and internet-linked electronics have impacted our lives. In order to meet the requirements of more flexible and adaptable paradigm shifts, wearable products may need to be seamlessly integrated. A great deal of effort has been made in the last two decades to develop flexible lithium-ion batteries (FLIBs). The selection of suitable flexible materials is important for the development of flexible electrolytes self-supported and supported electrodes. This review is focused on the critical discussion of the factors that evaluate the flexibility of the materials and their potential path toward achieving the FLIBs. Following this analysis, we present how to evaluate the flexibility of the battery materials and FLIBs. We describe the chemistry of carbon-based materials, covalent-organic frameworks (COFs), metal-organic frameworks (MOFs), and MXene-based materials and their flexible cell design that represented excellent electrochemical performances during bending. Furthermore, the application of state-of-the-art solid polymer and solid electrolytes to accelerate the development of FLIBs is introduced. Analyzing the contributions and developments of different countries has also been highlighted in the past decade. In addition, the prospects and potential of flexible materials and their engineering are also discussed, providing the roadmap for further developments in this fast-evolving field of FLIB research.

The Role of Multilevel Intercostal Nerve Block in Local Anesthetic Thoracoscopy.

BACKGROUND: Intercostal nerve block (ICNB) has long been used in thoracic surgery. Local anesthetic thoracoscopy (LAT) is performed under conscious sedation with local anesthesia at the port insertion site. This alone, however, does not anesthetize the parietal pleura from where biopsies are taken and patients can experience pain. OBJECTIVES: To compare LAT with multilevel ICNB versus standard care to determine whether it reduces pain during and post-LAT, its effect on analgesia use, the hospital length of stay (LOS), and related complications. METHODS: Prospective analysis of patients undergoing LAT between January and June 2021. In the ICNB group, levobupivacaine/xylocaine is administered at the angle of the rib immediately before LAT (up to 5 rib spaces). Visual Analog Score for pain (0 to 100 mm) was measured at 1 and 2 hours post-LAT and daily including analgesia use. RESULTS: Twenty patients (10 ICNB vs. 10 standard care group). The mean age is 68 years with 70% males. Visual Analog Score for pain in the ICNB group reduced by 55 mm at 1 and 2 hours post-LAT and 45 mm at day 1 ( P <0.05) (minimal clinically important difference >16 mm]. Median LOS was reduced by 50% in the ICNB group ( P <0.05). Paracetamol use reduced by 56% ( P <0.05). CONCLUSION: ICNB not only significantly reduces postprocedure pain but also reduces LOS.

Synthesis of Electrical Conductive Metal-Organic Frameworks for Electrochemical Applications.

Electrical conductivity is very important property of nanomaterials for using wide range of applications especially energy applications. Metal-organic frameworks (MOFs) are notorious for their low electrical conductivity and less considered for usage in pristine forms. However, the advantages of high surface area, porosity and confined catalytic active sites motivated researchers to improve the conductivity of MOFs. Therefore, 2D electrical conductive MOFs (ECMOF) have been widely synthesized by developing the effective synthetic strategies. In this article, we have summarized the recent trends in developing the 2D ECMOFs, following the summary of potential applications in the various fields with future perspectives.

Unlocking the potential of the tumor microenvironment for cancer therapy.

The tumor microenvironment (TME) holds a crucial role in the progression of cancer. Epithelial-derived tumors share common traits in shaping the TME. The Warburg effect is a notable phenomenon wherein tumor cells exhibit resistance to apoptosis and an increased reliance on anaerobic glycolysis for energy production. Recognizing the pivotal role of the TME in controlling tumor growth and influencing responses to chemotherapy, researchers have focused on developing potential cancer treatment strategies. A wide array of therapies, including immunotherapies, antiangiogenic agents, interventions targeting cancer-associated fibroblasts (CAF), and therapies directed at the extracellular matrix, have been under investigation and have demonstrated efficacy. Additionally, innovative techniques such as tumor tissue explants, "tumor-on-a-chip" models, and multicellular tumor spheres have been explored in laboratory research. This comprehensive review aims to provide insights into the intricate cross-talk between cancer-associated signaling pathways and the TME in cancer progression, current therapeutic approaches targeting the TME, the immune landscape within solid tumors, the role of the viral TME, and cancer cell metabolism.

Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing.

Mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders (LSDs). MPSs are caused by excessive accumulation of mucopolysaccharides due to missing or deficiency of enzymes required for the degradation of specific macromolecules. MPS I-IV, MPS VI, MPS VII, and MPS IX are sub-types of mucopolysaccharidoses. Among these, MPS III (also known as Sanfilippo) and MPS IV (Morquio) syndromes are lethal and prevalent sub-types. This study aimed to identify causal genetic variants in cases of MPS III and MPS IV and characterize genotype-phenotype relations in Pakistan. We performed clinical, biochemical and genetic analysis using Whole Genome Sequencing (WGS) in 14 Pakistani families affected with MPS III or MPS IV. Patients were classified into MPS III by history of aggressive behaviors, dementia, clear cornea and into MPS IV by short trunk, short stature, reversed ratio of upper segment to lower segment with a short upper segment. Data analysis and variant selections were made based on segregation analysis, examination of known MPS III and MPS IV genes, gene function, gene expression, the pathogenicity of variants based on ACMG guidelines and in silico analysis. In total, 58 individuals from 14 families were included in the present study. Six families were clinically diagnosed with MPS III and eight families with MPS IV. WGS revealed variants in MPS-associated genes including NAGLU, SGSH, GALNS, GNPTG as well as the genes VWA3B, BTD, and GNPTG which have not previously associated with MPS. One family had causal variants in both GALNS and BTD. Accurate and early diagnosis of MPS in children represents a helpful step for designing therapeutic strategies to protect different organs from permanent damage. In addition, pre-natal screening and identification of genetic etiology will facilitate genetic counselling of the affected families. Identification of novel causal MPS genes might help identifying new targeted therapies to treat LSDs.

HOTAIR in colorectal cancer: structure, function, and therapeutic potential.

lncRNAs play a vital part in cancer development by regulating gene expression. Among these, the lncRNA HOTAIR has gained considerable attention due to its entanglement in multiple cellular processes, including chromatin remodeling and gene regulation. HOTAIR has a complex structure consisting of multiple domains that interact with various protein complexes and RNA molecules. In colorectal cancer (CRC), HOTAIR expression is upregulated, and its overexpression has been correlated with poor patient prognosis and resistance to chemotherapy. HOTAIR has been found to regulate gene expression and promote cancer growth by interacting with specific miRNAs. In addition, HOTAIR has been implicated in the development of treatment resistance in colorectal cancer. To develop effective treatments, it's important to understand how HOTAIR regulates gene expression. This article discusses HOTAIR's structure, functions, and mechanisms in CRC and its potential as a target for therapy. The author also suggests future research directions to better understand HOTAIR's role in CRC progression and drug resistance.

Changes in lung cancer staging and emergency presentations during the first year of the COVID-19 pandemic.

Aim: This study retrospectively analyses the impact of the 1st year of the COVID-19 pandemic on route of presentation and staging in lung cancer compared to the 2 years before and after implementation of the Leicester Optimal Lung Cancer Pathway (LOLCP) in Leicester, United Kingdom. Method: Electronic databases and hospital records were used to identify all patients diagnosed with lung cancer in 2018 (pre-LOLCP), 2019 (post-LOLCP), and March 2020-2021 (post-COVID-19 lockdown). Information regarding patient characteristics, performance status, stage, and route of diagnosis was documented and analysed. Emergency presentation was defined as diagnosis of new lung cancer being made after unscheduled attendance to urgent or emergency care facility. Results: Following implementation of the LOLCP pathway, there was a significant decrease in emergency presentations from 26.8 to 19.6% (p = 0.002) with a stage shift from 33.9% early stage disease to 40.3%. These improved outcomes were annulled during the COVID-19 pandemic, with emergency presentations increasing to 38.9% (p < 0.001) and a reduction in early-stage lung cancer diagnoses to 31.5%. There was a 61% decline in 2 week wait referrals but no significant decline in the LOLCP direct-to-CT referrals. Conclusion: We have demonstrated a significant increase in late-stage lung cancer diagnoses and emergency presentations during the first year of the COVID-19 pandemic. The causes for these changes are likely to be multifactorial. The long-term effect on lung cancer mortality remains to be seen and is an important focus of future study.

Cancer Statistics in Pakistan From 1994 to 2021: Data From Cancer Registry.

PURPOSE: Pakistan has been systematically collecting cancer data since 1994 through cancer registries. METHODS: This article presents a comprehensive analysis of cancer statistics in Pakistan from 1994 to 2021, including incidence and patterns. RESULTS: The total number of patients with malignant neoplasm was 111,941, and the number of patients registered was 109,863. Most patients were from Punjab (67.6%) and Khyber Pakhtunkhwa (20.2%). Breast cancer (22.2%), colorectum cancer (5.6%), leukemia (5.3%), lip and oral cavity cancer, and non-Hodgkin lymphoma (5.1%) were the top five prevalent cancers in all age groups and sexes. Breast (24.2%), colorectum (6.2%), lip and oral cavity (5.8%), non-Hodgkin lymphoma (4.4%), and prostate cancers (4.0%) were most common in adults in both sexes. In both sexes, the most common cancers among children were Hodgkin lymphoma (20.1%), acute lymphoblastic leukemia (19.8%), non-Hodgkin lymphoma (11.6%), osteosarcoma (7.0%), and retinoblastoma (6.2%). Breast (45.9%), ovary and uterine adnexa (4.9%), lip and oral cavity (4.2%), cervix uteri (4.0%), and colorectum cancers (3.9%) were most common in adult females. In adult males, colorectum cancer (8.7%), prostate cancer (8.5%), lip and oral cavity cancer (7.6%), non-Hodgkin lymphoma (6.4%), and liver and intrahepatic bile duct cancers were the top five most common malignancies. CONCLUSION: It has been found that breast cancer, colorectum cancer, prostate cancer, leukemia, and bone cancer rates are among the highest in Pakistan. This information may be useful in assessing the effectiveness of future intervention strategies.

WNT5A: a double-edged sword in colorectal cancer progression.

The Wnt signaling pathway is known to play a crucial role in cancer, and WNT5A is a member of this pathway that binds to the Frizzled (FZD) and Receptor Tyrosine Kinase-Like Orphan Receptor (ROR) family members to activate non-canonical Wnt signaling pathways. The WNT5A pathway is involved in various cellular processes, such as proliferation, differentiation, migration, adhesion, and polarization. In the case of colorectal cancer (CRC), abnormal activation or inhibition of WNT5A signaling can lead to both oncogenic and antitumor effects. Moreover, WNT5A is associated with inflammation, metastasis, and altered metabolism in cancer cells. This article aims to discuss the molecular mechanisms and dual roles of WNT5A in CRC.