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The majority of naturally elicited antibodies against the HIV-1 envelope glycoproteins (Env) are non-neutralizing (nnAbs) because they are unable to recognize the Env trimer in its native "closed" conformation. Nevertheless, it has been shown that nnAbs have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC) provided that Env is present on the cell surface in its "open" conformation. This is because most nnAbs recognize epitopes that become accessible only after Env interaction with CD4 and the exposure of epitopes that are normally occluded in the closed trimer. HIV-1 limits this vulnerability by downregulating CD4 from the surface of infected cells, thus preventing a premature encounter of Env with CD4. Small CD4-mimetics (CD4mc) sensitize HIV-1-infected cells to ADCC by opening the Env glycoprotein and exposing CD4-induced (CD4i) epitopes. There are two families of CD4i nnAbs, termed anti-cluster A and anti-CoRBS Abs, which are known to mediate ADCC in the presence of CD4mc. Here, we performed Fab competition experiments and found that anti-gp41 cluster I antibodies comprise a major fraction of the plasma ADCC activity in people living with HIV (PLWH). Moreover, addition of gp41 cluster I antibodies to cluster A and CoRBS antibodies greatly enhanced ADCC-mediated cell killing in the presence of a potent indoline CD4mc, CJF-III-288. This cocktail outperformed broadly neutralizing antibodies and even showed activity against HIV-1-infected monocyte-derived macrophages. Thus, combining CD4i antibodies with different specificities achieves maximal ADCC activity, which may be of utility in HIV cure strategies.IMPORTANCEThe elimination of HIV-1-infected cells remains an important medical goal. Although current antiretroviral therapy decreases viral loads below detection levels, it does not eliminate latently infected cells that form the viral reservoir. Here, we developed a cocktail of non-neutralizing antibodies targeting highly conserved Env regions and combined it with a potent indoline CD4mc. This combination exhibited potent ADCC activity against HIV-1-infected primary CD4 + T cells as well as monocyte-derived macrophages, suggesting its potential utility in decreasing the size of the viral reservoir., Competing Interests: The authors declare no conflict of interest.

Objective: Cervical cancer results from persistent infection with high-risk human papillomavirus (HR-HPV) and the expression of E6 and E7 oncoproteins. E6 and E7 compromise the activity of p53 and Rb, the G1-S cell cycle checkpoint, and ATM-mediated DNA damage repair (DDR), which in turn increases reliance on ATR- and PARP-mediated DDR at the G2 cell cycle checkpoint. This study aimed to determine the effects of an ATR inhibitor (ATRi, AZD6738) and a PARP-inhibitor (PARPi, AZD2281) on HR-HPV+ cervical cancer cell lines., Methods: The effects of ATRi and PARPi, alone and in combination, on metabolic viability, cell cycle arrest, apoptosis, and DDR pathways in cervical cancer cell lines were evaluated in vitro, and the in vivo tumor response was evaluated using a xenograft model., Results: Cervical cancer cells were sensitive to ATRi and PARPi monotherapy. The combination therapy was only synergistic in reducing metabolic viability when exposed to ATRi first, followed by PARPi, owing to ATRi-mediated upregulation of PARP expression. Combination of ATRi and PARPi induced G2 cell cycle arrest and apoptosis. PARPi induced DNA damage and γH2AX phosphorylation, which was further increased by ATRi treatment. However, PARPi-induced Rad51 foci formation was reduced by ATRi treatment, suggesting the inhibition of homologous recombination repair. ATRi significantly reduced cervical cancer xenograft tumor growth and was not affected by simultaneous PARPi treatment at the doses studied., Conclusions: Our findings show that ATRi increased reliance on PARP for metabolic viability, the combination of ATRi and PARPi induced synthetic lethality in cervical cancer in vitro, and reduced tumor burden in vivo., Competing Interests: Declaration of competing interest Author K.M.M serves on the American Board of Obstetrics and Gynecology, and is a member of the NRG Oncology Cervix and Diversity Equity and Inclusion committees. The remaining authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Glory lily ( Gloriosa superba ), an ornamental climbing plant, contains the bioactive compound colchicine, attracting attention from the pharmaceutical industry. However, soilborne pathogens have emerged as a serious threat to the cultivation of glory lily, leading to substantial economic losses in the southern parts of India. Among these, the three major pathogens are Macrophomina phaseolina , Fusarium oxysporum , and Agroathelia rolfsii , causing dry root rot (also referred to as charcoal rot), wilt, and stem rot, respectively. Here, we characterized these pathogens using morphological characteristics and phylogenetic analysis of DNA sequences related to the internal transcribed spacer of ribosomal DNA, calmodulin ( CAL ), and translation elongation factor 1-alpha ( TEF-1α ). Furthermore, in the pathogenicity tests, the inoculation of M. phaseolina alone resulted in lesions measuring 7.54 ± 0.01 mm on tubers and 90% seedling mortality. This severity was comparable to the simultaneous inoculation of all three pathogens, indicating the prominence of dry root rot among soilborne diseases. This study marks the first detailed investigation of soilborne pathogens combined infection in G. superba , contributing to the understanding of fungal disease complexity in medicinal plants., Competing Interests: The author(s) declare no conflict of interest.

Background: Advancements in immuno-oncology have dramatically transformed cancer treatment. Immunotherapy, targeting immune check point proteins, notably Programmed cell death ligand 1 (PD-L1) and its receptor Programmed Cell Death-1 (PD-1) which modulate the activity of immune response in Head and Neck squamous cell carcinomas (HNSCC), is an area of much research. The immunohistochemical expression of PD-L1 in cancer cells has been proposed as a predictive biomarker for selecting candidates for immunotherapy. Thus, the present study was undertaken to study the expression of PD-L1 in the primary tumour cells and evaluate its correlation with various clinicopathological parameters and prognosis in tobacco associated oral squamous cell carcinomas (OSCC)., Methods: Expression of PD-L1 was investigated in 75 surgically resected cases of OSCC by immunohistochemistry and its association with different clinicopathological features and prognosis was analysed., Results: PD-L1 protein was detected in 68% (51 cases) of cases. Tumour stage (p = 0.04), lymph node (LN) metastasis (p < 0.01) and moderate to marked tumour infiltrating lymphocytes (TILs) (p < 0.05), significantly correlated with the PD-L1 expression in the primary tumour. PD-L1 expression did not show a significant association with overall survival (OS) rate, however, patients with positive PD-L1 expression showed a poorer survival rate. Patients exhibiting nodal positivity had the worst prognosis (p < 0.005)., Conclusion: These data demonstrated a significant association of ≥ 5% PD-L1 expression in the primary tumour and the presence of LN metastasis, moderate to marked TILs and advancing tumour stage, thus, making it a plausible immunotherapeutic target molecule in OSCC patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Two-dimensional transition metal dichalcogenides (TMDs), such as MoS 2 , hold great promise for next-generation electronics and optoelectronics due to their unique properties. However, the ultrathin nature of these materials renders them vulnerable to structural defects and environmental factors, which significantly impact their performance. Sulfur vacancies (V S ) are the most common intrinsic defects in MoS 2 , and their impact on device performance in oxidising environments remains understudied. This study investigates the impact of V S defects on the photoresponsivity of CVD-grown monolayer MoS 2 devices, when exposed to oxidising environments at high temperatures. Our findings reveal a dynamic process of defect generation and healing through oxygen passivation, leading to a significant difference in photocurrent between environments. Temperature-dependent analysis shows defect healing and a notable reduction in defect density upon cooling. This study provides crucial insights into the stability and performance of 2D materials-based devices under varying environmental conditions, essential for designing and controlling the performance of TMD-based devices. Our results pave the way for the development of robust and reliable 2D materials-based electronics and optoelectronics.

Atrazine (ATZ, C 8 H 14 ClN 5 ) is a widely used synthetic herbicide that contaminates drinking water. It is a known endocrine disruptor that disrupts various molecular pathways involved in hormone signaling, and DNA damage, and can cause reproductive disorders, including decreased fertility, and abnormal development of reproductive organs, as revealed in animal model studies. However, the effect of ATZ on steroidogenesis in the male reproductive system, especially reduction of ketosteroids to hydroxysteroids, remains unclear. This study investigated the toxicity of ATZ on the male reproductive system in the Wistar rat model, with an emphasis on its adverse effect on aldo-ketoreductase family 1 member C2 (AKR1C2). Male Wistar rats were administered ATZ for 56 days (duration of one spermatogenic cycle) through oral route, at 20, 40 and 60 mg/kg body weight (bw) doses. The results indicate that ATZ exposure affects the body weight, impairs sperm production, and decrease FSH, LH, and testosterone levels. Additionally, the down-regulation of key steroidogenic enzymes by ATZ disrupted the synthesis of testosterone, leading to decreased levels of this essential male hormone. On the other hand, the expression of AKR1C2 (mRNA and protein) in the testis was upregulated. The findings suggest that AKR1C2 plays a role in androgen metabolism. Furthermore, its overexpression may lead to alteration in the expression of genes in the connected pathway, causing an increase in the breakdown or inactivation of androgens, which would result in lower androgen levels and, thereby, lead to hypoandrogenism, as the combined effects of down-regulation of steroidogenic genes and up-regulation of AKR1C2. These findings reveal direct implication of disrupted AKR1C2 in male reproductive health and highlight the need for further research on the impact of environmental toxins on human fertility, ultimately providing for better patient care., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Nasopharyngeal carcinoma (NPC), a rare form of squamous cell carcinoma originating from the nasopharynx epithelium, exhibits a higher prevalence in southern China, Southeast Asia, the Arctic, North Africa, and the Middle East, with significant incidence in northeastern India, particularly Nagaland. Commonly presenting with nasal and otological symptoms, NPC diagnosis is challenging due to its diverse clinical manifestations. This case report highlights two atypical NPC cases: a 32-year-old female presenting with chronic headache and giddiness and a 22-year-old male with severe right-sided facial pain and trismus. Both cases underwent extensive diagnostic procedures, including imaging and biopsies, ultimately confirming NPC. Treatment involved radiotherapy and chemotherapy, resulting in significant symptom improvement. These cases underscore the importance of recognizing unusual NPC presentations to facilitate early diagnosis and treatment, improving patient outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vemula et al.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Diabetic retinopathy (DR) is a leading cause of blindness, yet its molecular mechanisms are unclear. Extracellular vesicles (EVs) contribute to dysfunction in DR, but the characteristics and functions of vitreous EVs are unclear. This study investigated the inflammatory properties of type 2 diabetic (db) vitreous EVs. EVs isolated from the vitreous of db and non-db donors were used for nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), immunogold staining, Western blotting, and proteomic analysis by mass spectrometry. Intracellular uptake of vitreous EVs by differentiated macrophages was evaluated using ExoGlow membrane labeling, and the impact of EVs on macrophage (THP-1) activation was assessed by cytokine levels using RT-qPCR. NTA and TEM analysis of db and non-db vitreous EVs showed non-aggregated EVs with a heterogeneous size range below 200 nm. Western blot detected EV markers (Alix, Annexin V, HSP70, and Flotillin 1) and an upregulation of Cldn5 in db EVs. While the db EVs were incorporated into macrophages, treatment of THP-1 cells with db EVs significantly increased mRNA levels of TNFα and IL-1β compared to non-db EVs. Proteomic and gene enrichment analysis indicated pro-inflammatory characteristics of db EVs. Our results suggest a potential involvement of EC-derived Cldn5+ EVs in triggering inflammation, offering a novel mechanism involved and presenting a possible therapeutic avenue for DR.

Background: The COVID-19 pandemic highlighted the need for timely, evidence-based rapid risk assessments (RRA) of infectious disease events to inform public health action during rapidly evolving situations with high uncertainty. In 2022, the Public Health Agency of Canada established a coordinated approach to public health risk assessment, including a methodology for qualitative RRA of infectious disease threats., Objective: To describe the RRA methodology and illustrate its use with examples from different infectious hazards of public health concern., Methods: The RRA methodology employs the risk pathway to describe the sequence of events leading from a hazard's source to the adverse event of concern and subsequent impacts; define specific questions to be addressed; and identify relevant knowledge gaps, limitations and recommendations. Qualitative likelihood and impact estimates are derived through integration of evidence review and expert opinion and are communicated together with corresponding levels of uncertainty. The impacts of the event are based on an assessment of the most likely spread scenario within Canada, considering individual-level impact on affected individuals, the impact on the general population and, if relevant, sub-groups at higher risk., Results: This RRA approach aligns with well-established international methods and provides flexibility to accommodate a broad range of risk questions. It has been implemented to estimate the risk of various threats of concern to Canada, including mpox, avian influenza A(H5N1) and measles., Conclusion: Given the broad range and complexity of public health hazards, RRAs provide a timely, coordinated and systematic process for characterizing and communicating the risk to inform risk mitigation and decision-making and to guide appropriate public health response., Competing Interests: Competing interests None.

The rise of carbapenem-resistant Klebsiella pneumoniae (CRKP) presents a significant global challenge in clinical and healthcare settings, severely limiting treatment options. This study aimed to utilize a bacteriophage as an alternative therapy against carbapenem-resistant K. pneumoniae . A novel lytic N4-like Klebsiella phage, vB&#95;kpnP&#95;KPYAP-1 (KPYAP-1), was isolated from sewage. It demonstrated efficacy against the K62 serotype polysaccharide capsule of bla OXA-48 -producing K. pneumoniae . KPYAP-1 forms small, clear plaques, has a latent period of 20 min, and reaches a growth plateau at 35 min, with a burst size of 473 plaque-forming units (PFUs) per infected cell. Phylogenetic analysis places KPYAP-1 in the Schitoviridae family, Enquatrovirinae subfamily, and Kaypoctavirus genus. KPYAP-1 employs an N4-like direct terminal repeat mechanism for genome packaging and encodes a large virion-encapsulated RNA polymerase. It lacks integrase or repressor genes, antibiotic resistance genes, bacterial virulence factors, and toxins, ensuring its safety for therapeutic use. Comparative genome analysis revealed that the KPYAP-1 genome is most similar to the KP8 genome, yet differs in tail fiber protein, indicating variations in host recognition. In a zebrafish infection model, KPYAP-1 significantly improved the survival rate of infected fish by 92% at a multiplicity of infection (MOI) of 10, demonstrating its potential for in vivo treatment. These results highlight KPYAP-1 as a promising candidate for developing phage-based therapies targeting carbapenemase-producing K. pneumoniae .

The tumor microenvironment (TME) is a dynamic and complex system that undergoes continuous changes in its network architecture, notably affecting redox homeostasis. These alterations collectively shape a diverse ecosystem actively supporting tumor progression by influencing the cellular and molecular components of the TME. Despite the remarkable clinical advancements in cancer immunotherapy, its spectrum of clinical utility is limited by the altered TME and inadequate tumor immunogenicity. Recent studies have revealed that some conventional and targeted therapy strategies can augment the efficacy of immunotherapy even in patients with less immunogenic solid tumors. These strategies provoke immunogenic cell death (ICD) through the ROS-dependent liberation of damage-associated molecular patterns (DAMPs). These DAMPs recognize and bind with Pattern Recognition Receptors (PRRs) on immune cells, activating and maturing defense cells, ultimately leading to a robust antitumor immune response. The present review underscores the pivotal role of redox homeostasis in orchestrating the transition of TME from a cold to a hot phenotype and the ROS-ICD axis in immune response induction. Additionally, it provides up-to-date insights into strategies that leverage ROS generation to induce ICD. The comprehensive analysis aims to develop ROS-based effective cancer immunotherapies for less immunogenic tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim The aim of this study is to analyze the demographic distribution (age and gender distribution), presenting symptoms, and evaluate the underlying etiology of hyponatremia among the study population. The presence of comorbidities and the volume status (hypovolemia, euvolemia, or hypervolemia) of elderly hyponatremic patients with varying severity of hyponatremia were assessed. Methods This cross-sectional, observational study was conducted in Dr. D. Y. Patil Hospital and Research Centre, Pune, India. After approval from the Institutional Ethics Sub-Committee (approval number: IESC/PGS/2022/09), it was conducted during the period between September 2022 and June 2024. The minimum sample size was calculated to be 96 with a confidence interval of 95% using WINIPEPI software (version 11.38). The lab values of serum sodium of all patients aged above 60 years admitted in wards and intensive care units (ICUs) were studied. Out of these hyponatremic patients, a sample size of 100 patients was randomly selected. Patients above 60 years and the patients who were on diuretic therapy were excluded from the study. Results The study included 100 elderly patients with a mean age of 73.25 ± 7.03 years, ranging from 64 to 86 years. Males predominated (63%), and severe hyponatremia (<125 mEq/L) was the most common, affecting 61% of patients. Generalized weakness (22%) and disorientation (17%) were the most frequently reported symptoms. Post-operative conditions (13%) and gastroenteritis (10%) were the leading causes. Most participants had no comorbidities (53%). Hypovolemia was present in 67% and euvolemia in 29% of the study subjects. Among hypovolemic patients, severe hyponatremia was present in 83.5% of patients. Conclusion This study highlights the significant burden of severe hyponatremia among elderly patients, particularly in male subjects and those with hypovolemia. Majority of the participants did not have any comorbidities. Additionally, the study emphasizes the need for heightened clinical vigilance in elderly patients presenting with generalized weakness and disorientation, as these were the most common symptoms associated with hyponatremia. The identification of post-operative conditions and gastroenteritis as leading causes further supports the need for comprehensive management strategies in elderly inpatients to prevent the occurrence and complications of hyponatremia., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Sub-Committee issued approval IESC/PGS/2022/09. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ande et al.)

Background and Aim: Achalasia cardia, a primary motility disorder of the esophagus, poses significant malnutrition risks. This study aims at comprehensively assessing the nutritional status in untreated achalasia patients, contrasting it with functional gastrointestinal disorders (FGIDs) cases and impact of per-oral endoscopic myotomy (POEM) on nutrition at one-year., Methods: We conducted a prospective study, including consecutive achalasia cases, from December 2021 to April 2022 at a tertiary care centre. Biochemical parameters, anthropometry, subjective global assessment (SGA) and malnutrition universal screening tool were used for nutritional assessment. Cases diagnosed with FGIDs served as controls., Results: As many as 118 cases (41.2 ± 13.9 years, 61% males) with achalasia and 200 controls (43.4 ± 11.9 years, 69% males) were included in the study. Sub-types of achalasia included type I (16.9%), II (76.3%) and III (6.8%). Overall, 38.1% and 6.8% cases were moderately and severely malnourished, respectively. As compared to controls, cases with achalasia had lower pre-albumin (19.4 vs. 25.2; p = 0.001), serum calcium (p = 0.012), vitamin D (p = 0.001), serum iron (p = 0.001), triceps fold thickness (p = 0.002) and hand-grip strength (p = 0.001). On univariate analysis, type-I achalasia, body mass index, % weight loss, lower esophageal sphincter pressures and Eckardt scores were predictors of malnourishment (SGA). On multivariate analysis, type of achalasia, mid arm circumference and low body mass index were significant predictors of malnourishment in cases with achalasia. There was significant improvement in the nutritional status after POEM at one-year follow-up., Conclusion: Achalasia patients demonstrate a notably higher risk of malnutrition compared to individuals with FGIDs. Nutritional status significantly improves after POEM. (NCT05161923)., (© 2024. Indian Society of Gastroenterology.)

Background and objective Hepatorenal syndrome (HRS) is a systemic disorder that affects both the kidneys and the liver. HRS refers to the occurrence of kidney failure in individuals with advanced liver cirrhosis, portal hypertension, and ascites, without any underlying kidney disease. The interplay of systemic and portal hemodynamics causes severe constriction of blood vessels in the kidneys, which defines HRS. The study aims to illuminate the demographic profiles, etiology, and outcomes of patients with HRS. Material and methods The study was designed as a prospective, cross-sectional, hospital-based observational study conducted at Dr. D.Y. Patil Medical College, Hospital, and Research Centre in Pimpri, Pune. The study period spans from September 2022 to June 2024. Before commencement, approval was obtained from the institutional ethics committee, and informed written consent was secured from all participating patients. The sample size consists of 100 patients diagnosed with HRS, selected from the general medicine outpatient department, wards, and ICU of Dr. D.Y. Patil Hospital and Research Centre. A comprehensive clinical history was recorded for all patients, focusing on the symptoms of cirrhosis and HRS, followed by a thorough examination for related signs and symptoms. Results Among the 100 patients included in this study on HRS, 25% (N=25) fell within the age range of 18-30 years, and 76% (N=76) were identified as male. Alcoholic cirrhosis accounted for 78% (N=78) of cases, with hepatitis B infection being the subsequent leading cause. The mortality rate was 12% (N=12) while the survival rate was 88% (N=88). Conclusion This study provides insights into the demographic profile, etiology, and outcomes of HRS. The results of this study contribute valuable insights into the complex nature of HRS, highlighting the importance of early detection and monitoring to optimize patient care., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Sub-Committee issued approval IESC/PGS/2022/01. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Borle et al.)

The fate and stability of messenger RNA (mRNA), from transcription to degradation is regulated by a dynamic shuttle of epigenetic modifications and RNA binding proteins in maintaining healthy cellular homeostasis and disease development. While Transforming Growth Factor Beta 1 (TGFβ1) has been implicated as a key regulator for diabetic retinopathy, a microvascular complication of diabetes, the RNA binding proteins post-transcriptionally regulating its expression remain unreported in the ocular context. Further, dysfunction of TGFβ1 signalling is also strongly associated with angiogenesis, inflammatory responses and tissue fibrosis in many eye conditions leading to vision loss. In this study, computational and molecular simulations were initially carried out to identify Human Antigen R (HuR) binding sites in TGFβ1 mRNA and predict the structural stability of these RNA-protein interactions. These findings were further validated through in vitro experiments utilizing Cobalt Chloride (CoCl 2 ) as a hypoxia mimetic agent in human retinal microvascular endothelial cells (HRMVEC). In silico analysis revealed that HuR preferentially binds to the 5'-UTR of TGFβ1 and displayed more stable interaction than the 3'UTR. Consistent with in silico analysis, RNA immunoprecipitation demonstrated a robust association between HuR and TGFβ1 mRNA specifically under hypoxic conditions. Further, silencing of HuR significantly reduced TGFβ1 protein expression upon CoCl 2 treatment. Thus, for the first time in ocular pathological milieu, direct evidence of HuR- TGFβ1 mRNA interaction under conditions of hypoxia has been reported in this study providing valuable insights into RNA binding proteins as therapeutic targets for ocular diseases associated with TGFβ1 dysregulation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Sharada Ramasubramanyan reports financial support was provided by the Science and Engineering Research Board, Department of Science and Technology, India. Sruthi Priya Mohan reports financial support was provided by Indian Council of Medical Research - Senior Research Fellowship. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Graphene quantum dots (GQDs) are an evolving class of carbon-based nanomaterial, seizing tremendous attention owing to their intense optical property, engineered shapes and structures, and good photostability. Being a zero-dimensional form of carbon structure, GQDs have superior photoluminescent behavior, tunable emission and absorption, excellent biocompatibility, low cytotoxicity, hydrophilic nature, modifying surface states. Their water dispersibility and functionalized surface structure, involving heteroatoms and various functional groups onto the surface of GQDs, make them particularly suitable for biological applications. Based on their absolute luminescence properties, GQDs emit blue, green, yellow, and red light under ultraviolet irradiation. Amongst the three colors, red luminescence can achieve deeper penetration of light into tissues, good cellular distribution, bio-sensing property, cell imaging, drug delivery, and serves as a better candidate for photodynamic therapy. The overall objective of this review is to provide a comprehensive overview of the synthesis methods for red fluorescence graphene quantum dots (RF-GQDs), critical comparative analyses of spectral techniques used for their characterization, the tunable photoluminescence mechanisms underpinning red emission, and the significance of chemically functionalizing GQDs' surface edges in achieving red fluorescence are discussed in depth. This review also discusses the effective biological applications and critical challenges associated with RF-GQDs are examined, providing insights into their future potential in clinical and industrial applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background:  In the last 2 years of the pandemic, a wide range of cases of post-COVID functional gastrointestinal disorders (PC-FGIDs) has been reported., Aim:  This case series aimed to investigate the role of homeopathic intervention in the treatment of PC-FGIDs., Methods:  This is a retrospective analysis of the clinical data of individuals who had suffered from PC-FGIDs that were diagnosed based on clinical symptoms using the Gastrointestinal Symptoms Rating Scale (GSRS) and treated exclusively with individualized homeopathic medicines. Cases that had undergone regular monthly assessment using the GSRS and had a Post-COVID-19 Functional Status (PCFS) score for up to 3 months were considered., Results:  Thirty cases were screened and twelve were included according to the study criteria. The mean age of seven women and five men was 36 years. GSRS and PCFS scores showed marked improvement in each of 10 cases within the 3-month treatment period., Conclusion:  Homeopathic intervention proved beneficial in 10 of 12 patients with PC-FGIDs. The findings may help researchers plan future controlled clinical studies in this field., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

Piperine is an amide alkaloid responsible for producing the pungent smell that comes from black pepper. Piperine has been explained to exhibit significant properties such as anti-rheumatic, anti-inflammatory, and antihypertensive effects. The aim of the study was to synthesize pyrrole ester from piperine and evaluate its anti-arthritis effects in adjuvant-induced arthritis female Wistar rats. In this study, pyrrole ester (AU-5) was designed, synthesized and evaluated for ant-arthritic activity in adjuvant-induced arthritis Wistar rats. The synthesized pyrrole ester (AU-5) was administered in three selected doses (20, 10 and 5 mg/kg) to the arthritic-induced model. The administered ester significantly inhibited the increase in arthritis index, paw and ankle joint swelling compared to the arthritic control group. Similarly, the treated rats exhibited a remarkable increase in body weight increase, improved haematological, biochemical, histopathological and radiological parameters. Moreover, the excess production of rheumatoid factor (RF), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was noticeably attenuated in all AU-5-treated rats. However, the spleen index, tumour necrosis factor (TNF-α) and interleukin-6 (IL-6) were distinctly lowered compared to arthritic control rats. Moreover, AU-5 showed promising liver protection by lowering the level of liver function markers Serum glutamic pyruvic transaminase (SGPT), Serum glutamic-oxaloacetic transaminase (SGOT) and alkaline phosphatase (ALP) in serum. Henceforth, it might be concluded that AU-5 has an anti-arthritic effect which can be credited to the down regulation of inflammatory markers and the pro-inflammatory cytokines., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Despite many recent studies on non-alcoholic fatty liver disease (NAFLD) therapeutics, the optimal treatment has yet to be determined. In this unfinished project, we combined secondary metabolites (SMs) from the gut microbiota (GM) and Hordeum vulgare (HV) to investigate their combinatorial effects via network pharmacology (NP). Additionally, we analyzed GM or barley - signalling pathways - targets - metabolites (GBSTMs) in combinatorial perspectives (HV, and GM). A total of 31 key targets were analysed via a protein-protein interaction (PPI) network, and JUN was identified as the uppermost target in NAFLD. On a bubble plot, we revealed that apelin signalling pathway, which had the lowest enrichment factor antagonize NAFLD. Holistically, we scrutinized GBSTM to identify key components (GM, signalling pathways, targets, and metabolites) associated with the Apelin signalling pathway. Consequently, we found that the primary GMs ( Eubacterium limosum , Eggerthella sp. SDG-2 , Alistipes indistinctus YIT 12060 , Odoribacter laneus YIT 12061 , Paraprevotella clara YIT 11840 , Paraprevotella xylaniphila YIT 11841 ) to ameliorate NAFLD. The molecular docking test (MDT) suggested that tryptanthrin-JUN is an agonist, conversely, dihydroglycitein-HDAC5, 1,3-diphenylpropan-2-ol-NOS1, and (10[(Acetyloxy)methyl]-9-anthryl)methyl acetate-NOS2, which are antagonistic conformers in the apelin signalling pathway. Overall, these results suggest that combination therapy could be an effective strategy for treating NAFLD.

The current work involves the fabrication of a MXene-Polythiophene (Ti 3 C 2 T x -PTh) composite via interfacial polymerization, alongside its deployment as a counter electrode (CE) or photocathode in dye-sensitized solar cells (DSSCs). The structural properties of the synthesized materials were investigated through a comprehensive array of techniques, including X-ray diffraction (XRD), fourier-transform infrared (FT-IR) spectroscopy, high resolution scanning electron microscopy (HRSEM), energy-dispersive X-ray analysis (EDAX), and X-ray photoelectron spectroscopy (XPS). The electrochemical performance, assessed via cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), revealed that the Ti 3 C 2 T x -PTh CE exhibits superior electro-catalytic activity, and reduction in charge transfer resistance compared to other individual CEs. These observations are in concordance with the data obtained from Tafel analysis. The incorporation of Ti 3 C 2 T x sheets into the composite significantly augmented its catalytic efficacy for triiodide reduction, manifesting in elevated short-circuit photocurrent density and enhanced fill factor metrics. A DSSC utilizing the Ti 3 C 2 T x -PTh CE exhibited a power conversion efficiency (PCE) of 5.83%, which stands on par with that of traditional Pt CEs. Thus, the Ti 3 C 2 T x -PTh CE material is posited as a viable, cost-efficient alternative to Pt, heralding a new era in the engineering of counter electrodes for the next generation of DSSCs., Competing Interests: The authors declare no competing conflict of interest., (This journal is © The Royal Society of Chemistry.)

Diabetes Mellitus presents a formidable challenge as one of the most prevalent and complex chronic diseases, exerting significant strain on both patients and the world economy. It is recognized as a common comorbidity among severely ill individuals, often leading to a myriad of micro- and macro-vascular complications. Despite extensive research dissecting the pathophysiology and molecular mechanisms underlying vascular complications of diabetes, relatively little attention has been paid to potential lung-related complications. This review aims to illuminate the impact of diabetes on prevalent respiratory diseases, including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), tuberculosis (TB), pneumonia infections, and asthma, and compare the vascular complications with other vascular beds. Additionally, we explore the primary mechanistic pathways contributing to these complications, such as the expression modulation of blood-tissue-barrier proteins, resulting in increased paracellular and transcellular permeability, and compromised immune responses rendering diabetes patients more susceptible to infections. The activation of inflammatory pathways leading to cellular injury and hastening the onset of these respiratory complications is also discussed.

Background/aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis., Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight-mass spectrometry. Correlation analyses were performed targeting the gut- microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased)., Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella&#95;uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC > 0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites., Conclusion: Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Advanced-stage endometrial cancer patients typically receive a combination of platinum and paclitaxel chemotherapy. However, limited treatment options are available for those with recurrent disease, and there is a need to identify alternative treatment options for the advanced setting. Our goal was to evaluate the pre-clinical efficacy and mechanism of action of Oklahoma Nitrone 007 (OKN-007) alone and in combination with carboplatin and paclitaxel in endometrial cancer. The effect of OKN-007 on the metabolic viability of endometrial cancer cells in both two- and three-dimensional (2D and 3D) cultures, as well as on clonogenic growth, in vitro was assessed. We also evaluated OKN-007 in vivo using an intraperitoneal xenograft model and targeted gene expression profiling to determine the molecular mechanism and gene expression programs altered by OKN-007. Our results showed that endometrial cancer cells were generally sensitive to OKN-007 in both 2D and 3D cultures. OKN-007 displayed a reduction in 3D spheroid and clonogenic growth. Subsequent targeted gene expression profiling revealed that OKN-007 significantly downregulated the immunosuppressive and immunometabolic enzyme indolamine 2,3-dioxygenase 1 (IDO1) (-11.27-fold change) and modulated upstream inflammatory pathways that regulate IDO1 expression (interferon- (IFN-), Jak-STAT, TGF-β, and NF-kB), downstream IDO1 effector pathways (mTOR and aryl hydrocarbon receptor (AhR)) and altered T-cell co-signaling pathways. OKN-007 treatment reduced IDO1, SULF2, and TGF-β protein expression in vivo, and inhibited TGF-β, NF-kB, and AhR- receptor-mediated nuclear signaling in vitro. These findings indicate that OKN-007 surmounts pro-inflammatory, immunosuppressive, and pro-tumorigenic pathways and is a promising approach for the effective treat endometrial cancer. Significance Statement Women with advanced and recurrent endometrial cancer have limited therapeutic options. OKN-007, which has minimal toxicity and is currently being evaluated in early-phase clinical trials for the treatment of cancer, is a potential new strategy for the treatment of endometrial cancer., (© 2024 The Authors. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.)

Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with complex mechanisms. The study aimed to comprehensively explore vitreous humor of diabetic and non-diabetic individuals, paving the way for identifying the potential molecular mechanisms underlying DR., Methods: Vitreous samples from type 2 diabetic and non-diabetic subjects, collected post-mortem, were analyzed using liquid chromatography-mass spectrometry. Pathway enrichment and gene ontology analyses were conducted to identify dysregulated pathways and characterize protein functions., Results: Pathway analysis revealed dysregulation in multiple metabolic and signaling pathways associated with diabetes, including glycerolipid metabolism, histidine metabolism, and Wnt signaling. Gene ontology analysis identified proteins involved in inflammation, immune response dysregulation, and calcium signaling. Notably, proteins such as Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2), Calcium homeostasis endoplasmic reticulum protein (CHERP), and Coronin-1A (CORO1A) were markedly upregulated in diabetic vitreous, implicating aberrant calcium signaling, inflammatory responses, and cytoskeletal reorganization in DR., Conclusions: Our study provides valuable insights into the intricate mechanisms underlying DR and highlights the significance of inflammation, immune dysregulation, and metabolic disturbances in disease progression. Identification of specific proteins as potential biomarkers underscores the multifactorial nature of DR. Future research in this area is vital for advancing therapeutic interventions and translating findings into clinical practice.

In the current study, polyaniline (PANI) modified two-dimensional Ti 3 C 2 T x MXene composites (PANI-Ti 3 C 2 T x ) are exploited as photocathodes in dye-sensitized solar cells (DSSCs). The study revealed that incorporating PANI into Ti 3 C 2 T x improved the material's electrochemical properties, owing to the presence of amino groups in PANI that enhanced the material's electrical conductivity and thereby facilitated more rapid ion transport. In addition, PANI enhanced the surface wettability of Ti 3 C 2 T x , resulting in an increase in the number of electroactive sites. The presence of PANI molecules in the interlayer and on the surface of Ti 3 C 2 T x was confirmed through X-ray diffraction (XRD), scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX), and X-ray photoelectron spectroscopy (XPS). Subsequently, electrochemical analysis of the PANI-Ti 3 C 2 T x photocathode or counter electrode (CE) revealed a commendable electrocatalytic activity with the iodide/triiodide electrolyte, a favourable charge transfer kinetics, and a charge transfer resistance as low as platinum. Additionally, at AM 1.5G, the performance of the DSSC constructed using the thermally decomposed Pt-CE was 8.3% when subjected to simulated 1 sun light, whereas the efficiency of the DSSC constructed using the as-prepared composite material was 6.9% under corresponding conditions. PANI-Ti 3 C 2 T x as the photocathode (CE) in a DSSC showed a higher power conversion efficiency (PCE) improvement than PANI CE and Ti 3 C 2 T x CE DSSCs, emphasizing its potent catalytic activity and quick mass transport of electron capability. By capitalizing on the conductivity and electrocatalytic property of the two components, the as-fabricated PANI-Ti 3 C 2 T x photocathode significantly increased the overall PCE of DSSCs. Furthermore, the DSSC utilizing the PANI-Ti 3 C 2 T x CE demonstrated exceptional reproducibility and stability. This underscores its consistently high performance and significant resistance to corrosion in the iodide/triiodide redox electrolyte environment. Overall, these findings show that the PANI-Ti 3 C 2 T x composite has the potential to be a competitive alternative to platinum-based CE materials for the development of DSSCs with exceptional performance.

Background: Multiple Sclerosis (MS) is a debilitating neurological disease affecting the central nervous system and significantly impacting patients' quality of life. MS is known as an autoimmune disease affecting the white matter. The disease involves inflammation, demyelination, and neurodegeneration, causing irreversible disabilities. Current treatments for MS target the inflammatory phase, with limited effects on long-term disability. While neuronal damage significantly contributes to MS pathology, mechanisms of neurodegeneration are not well studied., Methods: This study evaluated neurodegenerative changes in the retina during disease progression, using data collected from an experimental MS model (Experimental Autoimmune Encephalomyelitis, EAE). Utilizing Hematoxylin and Eosin-stained retinal sections and assessment using Optical Coherence Tomography (OCT), the study investigated the neurodegenerative changes, such as loss of cells in the retinal ganglion cell layer (GCL) and retinal thinning in the retina of the EAE model and the control groups., Results: Our results showed a significant reduction in the number of cells in the GCL of the EAE retina at two different time points studied, suggesting loss of neurons compared to the control group. Thickness measurements showed a reduction in the total retina and inner retinal layer thicknesses in the EAE retina compared to the controls. Our results indicate evidence of neurodegenerative changes in the retina of the experimental model of MS. No significant differences were observed between the percent losses of cells between the two time points studied. The pattern of cell loss suggests that neurodegeneration occurs at an earlier stage of disease progression., Conclusions: Overall, the retina is an excellent model to investigate neurodegeneration in MS, and possibly, loss of cells in the GCL could be used as an early indicator of neurodegeneration in MS and to identify novel therapeutic agents to treat the disease., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Periodontal diseases, chronic inflammatory conditions affecting oral health, are primarily driven by microbial plaque biofilm and the body's inflammatory response, leading to tissue damage and potential tooth loss. These diseases have significant physical, psychological, social, and economic impacts, necessitating effective management strategies that include early diagnosis, comprehensive treatment, and innovative therapeutic approaches. Recent advancements in biomanufacturing have facilitated the development of natural bioactive compounds, such as polyphenols, terpenoids, alkaloids, saponins, and peptides, which exhibit antimicrobial, anti-inflammatory, and tissue regenerative properties. This review explores the biomanufacturing processes-microbial fermentation, plant cell cultures, and enzymatic synthesis-and their roles in producing these bioactive compounds for managing periodontal diseases. The integration of these natural compounds into periodontal therapy offers promising alternatives to traditional treatments, potentially overcoming issues like antibiotic resistance and the disruption of the natural microbiota, thereby improving patient outcomes.

Ogilvie's syndrome represents an acute form of intestinal obstruction that occurs in the absence of a detectable mechanical blockage impeding fecal passage. Hence, it is also given the name of intestinal pseudo-obstruction. It has been deemed a disease of imbalance between the arms of the autonomic nervous system with an increase in parasympathetic outflow. Most often, it has an antecedent surgical or medical illness. There is evidence for the use of IV neostigmine in such cases to prevent imminent intestinal ischemia and perforation. In the case of a non-responder, decompression of the bowel using a colonoscope and surgery have also been tried to relieve the symptoms. In the case that follows, a middle-aged man developed progressive abdominal distension in the course of his recovery from an ischemic cerebrovascular accident. Initially, he received conservative treatment for 48 hours. Subsequently, he was given IV neostigmine, which relieved his symptoms., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kanitkar et al.)

Aim We examine the lipid profile and correlation of serum uric acid (SUA) levels in cases of hypertension and normotensives. Methods The current observational study spanned between April 2022 and April 2024. Throughout the research, 200 patients were examined; 100 of these patients were classified as Stage 1 or Stage 2 hypertensive (as per the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure), while the other 100 served as controls, meaning they did not have hypertension or any other medical condition that could lead to elevated SUA levels. Results It was revealed that the proportion of hypertension was higher in males compared to females. Of the total male patients, most (41.1%) patients had grade 1 hypertension and grade 2 hypertension, while among females, 20% had grade 1 hypertension. It was seen that as age increases, systolic blood pressure (SBP) and diastolic blood pressure (DBP) also rise among the two study groups, although the correlation was not statistically significant between blood pressure level and age of study subjects. The hypertensive patients have increased SBP and DBP levels when compared to the control group, which is significant. The lipid profile shows that the hypertensive subjects had significantly higher mean low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglyceride levels than controls. SUA levels were observed to be elevated in the hypertensive subjects implying a positive correlation between the level of uric acid and blood pressures. Conclusion We found evidence that hyperuricemia and hypertension go hand in hand. A statistically noteworthy positive connection was found between the systolic blood pressures and lipid profiles of the patients. Hypertensive patients were found to have hyperlipidemia, whereas normotensive controls had normal lipid profiles. Moreover, it was seen that there was a positive correlation between SBP and chronological age in hypertensive cases, although this was statistically not significant., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ahlawat et al.)

Background: Little leaf disease caused by phytoplasma infection is a significant threat to eggplant (also known as brinjal) cultivation in India. This study focused on the molecular characterisation of the phytoplasma strains and insect vectors responsible for its transmission and screening of brinjal germplasm for resistance to little leaf disease., Results: Surveys conducted across districts in the Tamil Nadu state of India during 2021-2022 showed a higher incidence of phytoplasma during the Zaid (March to June), followed by Kharif (June to November) and Rabi (November to March) seasons with mean incidence ranging from 22 to 27%. As the name indicates, phytoplasma infection results in little leaf (reduction in leaf size), excessive growth of axillary shoots, virescence, phyllody, stunted growth, leaf chlorosis and witches' broom symptoms. PCR amplification with phytoplasma-specific primers confirmed the presence of this pathogen in all symptomatic brinjal plants and in Hishimonus phycitis (leafhopper), providing valuable insights into the role of leafhoppers in disease transmission. BLAST search and phylogenetic analysis revealed the phytoplasma strain as "Candidatus Phytoplasma trifolii". Insect population and disease dynamics are highly influenced by environmental factors such as temperature, relative humidity and rainfall. Further, the evaluation of 22 eggplant accessions revealed immune to highly susceptible responses where over 50% of the entries were highly susceptible. Finally, additive main effect and multiplicative interaction (AMMI) and won-where biplot analyses identified G18 as a best-performing accession for little leaf resistance due to its consistent responses across multiple environments., Conclusions: This research contributes essential information on little leaf incidence, symptoms, transmission and resistance profiles of different brinjal genotypes, which together ensure effective and sustainable management of this important disease of eggplants., (© 2024. Crown.)

The majority of naturally-elicited antibodies against the HIV-1 envelope glycoproteins (Env) are non-neutralizing (nnAbs), because they are unable to recognize the Env timer in its native "closed" conformation. Nevertheless, it has been shown that nnAbs have the potential to eliminate HIV-1-infected cells by Antibody-Dependent Cellular Cytotoxicity (ADCC) provided that Env is present on the cell surface in its "open" conformation. This is because most nnAbs recognize epitopes that become accessible only after Env interaction with CD4 and the exposure of epitopes that are normally occluded in the closed trimer. HIV-1 limits this vulnerability by downregulating CD4 from the surface of infected cells, thus preventing a premature encounter of Env with CD4. Small CD4-mimetics (CD4mc) sensitize HIV-1-infected cells to ADCC by opening the Env glycoprotein and exposing CD4-induced (CD4i) epitopes. There are two families of CD4i nnAbs, termed anti-cluster A and anti-CoRBS Abs, which are known to mediate ADCC in the presence of CD4mc. Here, we performed Fab competition experiments and found that anti-gp41 cluster I antibodies comprise a major fraction of the plasma ADCC activity in people living with HIV (PLWH). Moreover, addition of gp41 cluster I antibodies to cluster A and CoRBS antibodies greatly enhanced ADCC mediated cell killing in the presence of a potent indoline CD4mc, CJF-III-288. This cocktail outperformed broadly-neutralizing antibodies and even showed activity against HIV-1 infected monocyte-derived macrophages. Thus, combining CD4i antibodies with different specificities achieves maximal ADCC activity, which may be of utility in HIV cure strategies., Competing Interests: CONFLICT OF INTEREST The authors declare no competing interests.

Electrically connected and plasmonically enhanced molecular junctions combine the optical functionalities of high field confinement and enhancement (cavity function), and of high radiative efficiency (antenna function) with the electrical functionalities of molecular transport. Such combined optical and electrical probes have proven useful for the fundamental understanding of metal-molecule contacts and contribute to the development of nanoscale optoelectronic devices including ultrafast electronics and nanosensors. Here, we employ a self-assembled metal-molecule-metal junction with a nanoparticle bridge to investigate correlated fluctuations in conductance and tunneling-induced light emission at room temperature. Despite the presence of hundreds of molecules in the junction, the electrical conductance and light emission are both highly sensitive to atomic-scale fluctuations-a phenomenology reminiscent of picocavities observed in Raman scattering and of luminescence blinking from photoexcited plasmonic junctions. Discrete steps in conductance associated with fluctuating emission intensities through the multiple plasmonic modes of the junction are consistent with a finite number of randomly localized, point-like sources dominating the optoelectronic response. Contrasting with these microscopic fluctuations, the overall plasmonic and electronic functionalities of our devices feature long-term survival at room temperature and under an electrical bias of a few volts, allowing for measurements over several months., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Still's disease is frequently a condition of exclusion for patients with an unidentified cause of fever. Accompanying symptoms typically include fever, arthralgia, and a transient skin rash. The underlying pathophysiology indicates an autoimmune origin. Diagnosis is primarily clinical, often utilizing the Yamaguchi criteria. The case in question involves a 19-year-old male presenting with high-grade fever and paralytic ileus. The patient received intravenous glucocorticoids and cyclophosphamide, resulting in a rapid clinical improvement. During the follow-up, tofacitinib was initiated based on the clinical response observed., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kanitkar et al.)

Integrating MXene into perovskite solar cells (PSCs) has heralded a new era of efficient and stable photovoltaic devices owing to their supreme electrical conductivity, excellent carrier mobility, adjustable surface functional groups, excellent transparency and superior mechanical properties. This review provides a comprehensive overview of the experimental and computational techniques employed in the synthesis, characterization, coating techniques and performance optimization of MXene additive in electrodes, hole transport layer (HTL), electron transport layer (ETL) and perovskite photoactive layer of the perovskite solar cells (PSCs). Experimentally, the synthesis of MXene involves various methods, such as selective etching of MAX phases and subsequent delamination. At the same time, characterization techniques encompass X-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy, which elucidate the structural and chemical properties of MXene. Experimental strategies for fabricating PSCs involving MXene include interfacial engineering, charge transport enhancement, and stability improvement. On the computational front, density functional theory calculations, drift-diffusion modelling, and finite element analysis are utilized to understand MXene's electronic structure, its interface with perovskite, and the transport mechanisms within the devices. This review serves as a roadmap for researchers to leverage a diverse array of experimental and computational methods in harnessing the potential of MXene for advanced PSCs.

This study presents the synthesis of advanced nanomaterials derived from the hedge-grown herbal plant, Borreria hispida , and explores their environmental and biological applications. Using a one-step hydrothermal synthesis method, carbon dots derived from Borreria hispida (BHCD) were fabricated and thoroughly characterized through XRD, TEM, FTIR, CHNS, UV-visible, and PL spectroscopy analyses. Under UV illumination, these plant-based carbon dots demonstrated exceptional water solubility, notable photo stability, and a high quantum yield of 40.8%. The average particle size of BHCD was absorbed around 0.5 to 3.5 nm, contributing to superior selectivity and sensitivity in detecting Fe 3+ ions, with a limit of detection of 1.2 × 10 -6 M. Investigation into the sensing mechanism revealed a binding model wherein two carbon atom molecules bind to one Fe 3+ atom in a 2 : 1 ratio for BHCDs and Fe 3+ interactions. Additionally, the effectiveness of the developed fluorescent probe for Fe 3+ detection was validated using real water samples from ponds and lakes, highlighting its potential for environmental monitoring applications. Furthermore, the biological effects of BHCD were evaluated through cytotoxic assays, demonstrating significant inhibitory effects on MCF7 breast cancer cell lines, with a maximum cell viability of 60%. This research underscores the multifaceted potential of BHCD in environmental monitoring and biomedical applications., Competing Interests: The author declares no competing financial interest., (This journal is © The Royal Society of Chemistry.)

The genetic alteration in the antioxidant gene Glutathione-S-Transferases Pi 1 (GSTP1) namely GSTP1*IIe105Val (rs1695) and GSTP1*Ala114Val (rs1138272) changes the individual susceptibility to cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) by altering the substrate binding and catalytic activity. This study aims to investigate the association of GSTP1 rs1695 and rs1138272 polymorphism with CVD development in T2DM patients. Genotyping was performed with 400 study participants-group I: control; group II: T2DM; group III: CVD; and group IV: T2DM/CVD [n = 100 each] by PCR-RFLP. The rs1695 and rs1138272 polymorphism were docked against NPACT and NUBBE database and virtually screened using glide. The study reported that rs1695 polymorphism was associated with T2DM risk under dominant and allelic genetic models [OR = 1.97(1.08-3.59) p = 0.02 and OR = 1.79(1.20-2.66) p = 0.003, respectively]. The val/val genotype, dominant, recessive model, and T allelic genetic model were associated with increased CVD risk [OR = 4.15(1.97-8.73) p =  < 0.01; OR = 3.16(1.65-6.04) p =  < 0.01; OR = 3.47(1.91-6.31) p =  < 0.01; and OR = 2.94(1.95-4.43) p =  < 0.01, respectively]. In contrast, rs1695 polymorphism was not associated with CVD development among patients with T2DM. In rs1138272, the wild genotype was only detected and neither heterozygous nor val/val genotype was observed. The docking analysis revealed that the Ile105Val mutation plays a significant role in altering the GSTP1 capacity compared to the Ala115Val mutation. This suggests that the Ile105Val mutation has a greater impact on the protein's structure, function, or susceptibility to diseases compared to the Ala115Val mutation. In summary, genetic alteration in GSTP1 rs1695 potentially contributes to an increased risk of T2DM and CVD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An autoimmune polyradiculoneuropathy, Guillain-Barré syndrome (GBS) is an acute, rapidly progressive, and fulminant one. Rapidly developing motor weakness along with absent reflexes, with or without sensory impairment, is the hallmark of GBS. GBS is never a hereditary entity; it is always acquired by the individual. Here, we present an interesting case of GBS in a 37-year-old male patient presenting with lower limb weakness for one day which had progressed to upper limb weakness in a day. There was a history of fever and loose stools four days back. On examination, vitals were within normal limits including single breath count. Central nervous system (CNS) examination revealed as follows: bicep jerk, tricep jerk, and supinator jerk were National Institute of Neurological Disorders and Stroke (NINDS) scale grade 2 in bilateral upper limbs. Knee jerk was NINDS scale grade 3 in bilateral lower limbs, which was unusual considering that GBS presents with areflexia or reduced reflexes. Ankle jerk was absent in bilateral lower limbs. Plantars were mute bilaterally. Nerve conduction study was suggestive of axonal and demyelinating motor neuropathy involving all four limbs. The patient was planned for intravenous immunoglobulin at a dose of 2 g/kg/day for five days but developed an allergic reaction to the first dose; hence, the therapy was discontinued, and the option of plasmapheresis was given to which the patient refused. This is a report of a case of GBS with hyperreflexia which is an uncommon entity in the Indian subcontinent., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ahlawat et al.)

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4 + T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity., (© 2024. The Author(s).)

Tuberculosis (TB) remains a significant global health concern, particularly with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). Traditional methods for diagnosing drug resistance in TB are time-consuming and often lack accuracy, leading to delays in appropriate treatment initiation and exacerbating the spread of drug-resistant strains. In recent years, artificial intelligence (AI) techniques have shown promise in revolutionizing TB diagnosis, offering rapid and accurate identification of drug-resistant strains. This comprehensive review explores the latest advancements in AI applications for the diagnosis of MDR-TB and XDR-TB. We discuss the various AI algorithms and methodologies employed, including machine learning, deep learning, and ensemble techniques, and their comparative performances in TB diagnosis. Furthermore, we examine the integration of AI with novel diagnostic modalities such as whole-genome sequencing, molecular assays, and radiological imaging, enhancing the accuracy and efficiency of TB diagnosis. Challenges and limitations surrounding the implementation of AI in TB diagnosis, such as data availability, algorithm interpretability, and regulatory considerations, are also addressed. Finally, we highlight future directions and opportunities for the integration of AI into routine clinical practice for combating drug-resistant TB, ultimately contributing to improved patient outcomes and enhanced global TB control efforts., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, K et al.)

Guilandina bonduc L. is popularly known as a fever nut that grows widely in evergreen forests and moist deciduous forests with a pantropical distribution. The plant is highly therapeutic in various systems of medicine, including Ayurveda, Siddha, and homeopathy. The purpose of this review is to analyze the published data on G. bonduc, including traditional uses, taxonomic position, botanical description, phytochemistry, pharmacological properties, and toxicological assessment of its various parts. Phytochemical and pharmacological studies were the main focus of this review. The previously published research on G. bonduc was tracked from scientific databases such as Online Library, Google, Taylor and Francis, PubMed, Research Gate, Scopus, Springer, Wiley, Web of Sciences. Numerous phytochemical, pharmaceutical, and pharmacological studies have been carried out on the various parts of G. bonduc. To date, more than 97 phytochemicals have been isolated from the leaves, roots, stems, stem bark, flowers, twigs, and seeds of this plant. The phytochemicals isolated from the plants are flavonoids, homoisoflavonoids, terpenoids, diterpenoids, steroids, fatty acids, alkanes, acids, phenols, ketones, esters, amides, azides, silanes, and ether groups. This plant has been extensively studied in in vitro and in vivo pharmacological experiments, where it showed analgesic, anti-inflammatory, antioxidant, antiviral, antidiabetic, abortive, anticataleptic, immunomodulatory, and antiestrogenic effects. This comprehensive review revealed that phytochemicals isolated from various parts of G. bonduc have significant therapeutic efficacy, with promising anticancer, antidiabetic, hepatoprotective, antioxidant, and antimicrobial activities. This review provides a good source of information for the development of a drug using modern scientific tools, in view of its underexplored traditional uses. Further studies on preclinical and clinical trials and toxicological studies on the bioactive molecules of G. bonduc to validate its traditional uses are warranted., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Autistic students experience lower college graduation rates than their peers, affecting future opportunities. Self-advocacy is crucial for successful adaptation in postsecondary settings and is documented as a challenge for autistic students. The purpose of the study was to examine autistic college students' engagement in self-advocacy and specific college-related challenges as compared to their neurodivergent and neurotypical peers., Method: This study used a cross-sectional survey design to compare perceptions related to self-advocacy and college-related challenges across three groups of students: autistic students, students with a disability other than autism, and nondisabled students. Descriptive and inferential statistics were used to compare survey responses across groups., Results: Differences in the groups' perceptions of their engagement in overall self-advocacy and specific self-advocacy strategies were evident. Autistic students rated themselves significantly lower on self-advocacy than did students with other disabilities. When compared to their nondisabled peers, the autistic students and those with other disabilities were less likely to report comfort interacting in the classroom, including less interest in group work, and more difficulty interacting with unfamiliar peers. In addition, the autistic students were more likely to report difficulty recognizing the need for academic assistance when compared to both peer groups. Autistic students also reported greater social challenges in the college setting than their nondisabled peers, and both neurodivergent groups of students reported significantly more challenges, overall, navigating the college setting than did their nondisabled peers., Conclusions: Findings highlight the need for systematic, individualized self-advocacy supports for autistic and other neurodivergent college students. In addition, findings show the need to educate peers and professors about autism and self-advocacy to foster a welcoming college environment. Finally, findings suggest the need for increased social support and opportunities for social integration within postsecondary settings. Speech-language pathologists play a critical role in implementing these next steps.

Disruptions in polyamine metabolism have been identified as contributing factors to various central nervous system disorders. Our laboratory has previously highlighted the crucial role of polyamine oxidation in retinal disease models, specifically noting elevated levels of spermine oxidase (SMOX) in inner retinal neurons. Our prior research demonstrated that inhibiting SMOX with MDL 72527 protected against vascular injury and microglial activation induced by hyperoxia in the retina. However, the effects of SMOX inhibition on retinal neovascularization and vascular permeability, along with the underlying molecular mechanisms of vascular protection, remain incompletely understood. In this study, we utilized the oxygen-induced retinopathy (OIR) model to explore the impact of SMOX inhibition on retinal neovascularization, vascular permeability, and the molecular mechanisms underlying MDL 72527-mediated vasoprotection in the OIR retina. Our findings indicate that inhibiting SMOX with MDL 72527 mitigated vaso-obliteration and neovascularization in the OIR retina. Additionally, it reduced OIR-induced vascular permeability and Claudin-5 expression, suppressed acrolein-conjugated protein levels, and downregulated P38/ERK1/2/STAT3 signaling. Furthermore, our results revealed that treatment with BSA-Acrolein conjugates significantly decreased the viability of human retinal endothelial cells (HRECs) and activated P38 signaling. These observations contribute valuable insights into the potential therapeutic benefits of SMOX inhibition by MDL 72527 in ischemic retinopathy.

The present research examined patulin's presence across the whole supply chain of selected fruits. A comprehensive analysis was conducted on 442 samples of fruits (oranges, apples, apricots, lemons, and guava) to determine the presence of patulin contamination. This analysis used Liquid Chromatography (HPLC) with a UV detector. The findings indicate that 17, 23, and 28 % of selected fruit samples tested positive for patulin levels in farm, transportation, and market samples. However, the sample collected during the transportation step showed that 56 % (percentage of positive samples) of fruits have patulin levels greater than 50 μg/kg, and 41 % (percentage of positive samples) have greater levels than 50 μg/kg in market samples. The findings of the one-way analysis of variance indicated that no statistically significant variation existed between the amounts of patulin across the various stages of the food supply chain system (p > 0.05). Nevertheless, the analysis of the correlation study, namely Kendall's tau&#95;b and Spearman's rho, denote a robust association between the levels of patulin and the food supply system. The apple samples exhibited the most significant average dietary intake of patulin, with an average value of 0.11 μg/kg bw/day. The maximum mean hazard quotient (HQ) of 0.28 was also recorded. The prevalence and incidence of patulin in specific fruits were found to be relatively high, and it was observed that market samples had elevated levels of patulin in the selected fruits., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause chronic hepatitis with important clinical differences. HCV causes hepatic steatosis and insulin resistance, while HBV confers increased risk of liver cancer. We hypothesised these differences may be due to virus-specific effects on mitochondrial function., Methods: Seahorse technology was utilised to investigate effects of virus infection on mitochondrial function. Cell based assays were used to measure mitochondrial membrane potential and quantify pyruvate and lactate. Mass spectrometry was performed on mitochondria isolated from HBV expressing, HCV infected and control cells cultured with isotope-labelled amino acids, to identify proteins with different abundance. Altered expression of key mitochondrial proteins was confirmed by real time PCR and western blot., Results: Reduced mitochondrial function and ATP production were observed with HCV infection and HBV expression. HCV impairs glycolysis and reduces expression of genes regulating fatty acid oxidation, promoting lipid accumulation. HBV causes lactate accumulation by increasing expression of lactate dehydrogenase A, which converts pyruvate to lactate. In HBV expressing cells there was marked enrichment of pyruvate dehydrogenase kinase, inhibiting conversion of pyruvate to acetyl-CoA and thereby reducing its availability for mitochondrial oxidative phosphorylation., Conclusions: HCV and HBV impair mitochondrial function and reduce ATP production. HCV reduces acetyl-CoA availability for energy production by impairing fatty acid oxidation, causing lipid accumulation and hepatic steatosis. HBV has no effect on fatty oxidation but reduces acetyl-CoA availability by disrupting pyruvate metabolism. This promotes lactic acidosis and oxidative stress, increasing the risk of disease progression and liver cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)