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Introduction: Hydroxychloroquine (HCQ) is a medicine that has mainly been used to treat malaria. During the recent Coronavirus Disease-2019 (COVID-19) period, an abrupt spike in the sale of HCQ has been found. The repurposing of this drug in the treatment of COVID-19 was not only found to be ineffective but also showed many side effects. The adverse effects of the enormous exposure to this drug should be unveiled. Aim: To evaluate the acute effect of HCQ exposure on the male reproductive system by analysing the changes in antioxidant enzyme levels in testicular tissue, sperm quality, and histopathological assessment of testicular tissue using male albino rats as the subject model. Materials and Methods: The present experimental study was done by using male albino rats as the subject model. It was conducted in the laboratory of the Department of Human Physiology at Raja NL Khan Women’s College (Autonomous) in Medinipur, West Bengal, Kolkata, India, from the last week of June 2023 to the first week of August 2023. A total 10 male albino rats were obtained and randomly divided into two groups (n=5 in each group), control and HCQ-treated, and were given plain drinking water and 33 mg/kg/day HCQ, respectively, for six consecutive days through oral gavage. After the treatment tenures, rats were euthanised, and antioxidant enzymatic activity was measured by a spectrophotometer. Sperm quality and testicular histopathology were studied. A two-tailed t-test was used to compare the parameters of the control and HCQ-treated groups. Results: The total testicular weight of the control group was 2.37±0.17 g, in contrast treated group had a significantly lower testicular weight of 1.98±0.19 g. A significant decrease in total testicular protein in the treated group was found, i.e., 28.86±3.03 mg/g of tissue, compared to the control group, i.e., 60.46±2.85 mg/g of tissue. The sperm count of the control group was 4.51±0.06 million/ml of suspension, while the treated group had a significantly lower sperm count, i.e., 2.73±0.11 million/mL of suspension. The percentages of sperm motility and viability in the control group were 86±1.63% and 94±1.33%, respectively, but in the treated group, the percentages were significantly lower, i.e., 22.66±1.35% and 24±1.78%, respectively. The increasing sperm anomalies after HCQ exposure indicate poor sperm quality. Conclusion: Infertility or reduced fertility can result from testicular dysfunction, in continuation, decrease in sperm count, motility, viability, together with abnormalities in sperm morphology, was observed after this exposure. Thus, the present study provides insight into the adverse effects of the use of this drug, which might be associated with male infertility.

Abstract Studies on the neural correlates of navigation in 3D environments are plagued by several issues that need to be solved. For example, experimental studies show markedly different place cell responses in rats and bats, both navigating in 3D environments. In this study, we focus on modelling the spatial cells in rodents in a 3D environment. We propose a deep autoencoder network to model the place and grid cells in a simulated agent navigating in a 3D environment. The input layer to the autoencoder network model is the HD layer, which encodes the agent’s HD in terms of azimuth (θ) and pitch angles (ϕ). The output of this layer is given as input to the Path Integration (PI) layer, which computes displacement in all the preferred directions. The bottleneck layer of the autoencoder model encodes the spatial cell-like responses. Both grid cell and place cell-like responses are observed. The proposed model is verified using two experimental studies with two 3D environments. This model paves the way for a holistic approach using deep neural networks to model spatial cells in 3D navigation.

Introduction: Gestational Diabetes Mellitus (GDM) is a chronic and progressive disease characterised by changes in the metabolism of carbohydrates, lipids, and proteins, leading to glucose intolerance. The foetal heart in GDM is affected throughout the gestational period, which may result in hyperplasia and hypertrophy of myocardial cells. Aim: To determine the cardiac function and structural changes in infants of gestational diabetic mothers using Doppler-echocardiographic data. Materials and Methods: A cross-sectional analytical study was conducted on 30 infants of mothers with GDM and 30 infants of non diabetic mothers at the Department of Physiology, R.G. Kar Medical College and Hospital, in collaboration with the Departments of Paediatric Medicine and Cardiology from January 2023 to August 2023. Neonatal screening echocardiography was performed by a cardiologist using a Philips Echocardiograph machine, Model: EPIQ 7C, Software Version: 4.0.2, with a linear convex probe of S8-3 MHz frequency to assess cardiac structure and function using 2D, M mode, and Conventional Doppler. The parameters studied included aortic root diameter (mm), left atrial diameter (mm), Interventricular Septal (IVS) in diastole (mm), left ventricular posterior wall thickness in diastole (mm), left ventricular internal diameter in diastole (mm), left ventricular internal diameter in end systole (mm), left ventricular fractional shortening (%), and left ventricular ejection fraction (%). Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version-20.0 with an Independent Student’s t-test. Results: The mean gestational age for the cases was 38.50±2.57 weeks and 39.30±1.97 weeks for controls. The mean maternal age for cases was 25±4.37 years and for controls was 27±5.03 years. The left atrial diameter in cases (12.83±2.14 mm) was significantly smaller than that of the control (14.20±0.55 mm). The left ventricular posterior wall diameter in diastole was significantly increased in cases (4.53±0.50 mm) compared to controls (3.87±0.35 mm). Significant differences were observed in the interventricular septum in diastole {cases: 4.73±0.45 mm, control: 3.97±0.32 mm} and in the left ventricular internal diameter in end systole {cases: 12.30±1.84 mm, control: 13.83±1.02 mm} between cases and controls. Aortic root diameter was increased in 13.3% of cases. The percentage of left ventricular fractional shortening (cases: 35.47±3.74 %, Control: 38.53±2.43 %), Left Ventricular Ejection fraction (cases: 67.63±4.52 %, control: 72.17±4.89 %) were significantly decreased in cases compared to control. Conclusion: The present study demonstrated the development of ventricular hypertrophy and compromised myocardial contractility in infants of diabetic mothers.

Introduction: Understanding the intricate root canal system of mandibular incisors is crucial for successful root canal therapy. Variations in canal anatomy pose challenges in diagnosis and treatment planning, emphasising the need for comprehensive evaluation methods. Aim: To evaluate and assess the root canal configuration of permanent mandibular incisors based on Vertucci’s classification using periapical radiographs and correlating the same with the gold standard decalcification and dye-penetration technique. Materials and Methods: The current in-vitro study was carried out from December 2018 to March 2019 in the Department of Conservative Dentistry and Endodontics, Dr. R. Ahmed Dental College and Hospital, Kolkata, West Bengal, India. It analysed the root canal morphology of mandibular central and lateral incisors using radiographic examination and decalcification-dye penetration evaluation. Data from 50 central and 50 lateral incisors (100 mandibular incisors) were procured and were assessed and subsequently analysed statistically using International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) Statistics for Windows, Version 27.0 (Armonk, NY: IBM Corp). The study outcome included assessing the various canal types and configurations, types of canals (straight/curved), and the position of the apical foramen (labial/lingual) by both techniques. The existence of agreement was also tested using statistical analysis by the kappa (κ) coefficient between the two techniques with an alpha level of 5%. Results: The radiological findings of mandibular central incisors revealed a predominant presence of Type-I canals, constituting 66 (66%) cases, according to Vertucci’s classification. Decalcification-dye penetration evaluation of central incisors showed a similar trend, with Type-I canals exhibiting a significantly higher percentage 35 (70%) compared to other canal types (p

The skin, as the first physical barrier for invading pathogens, also serves as an immunologically active organ. Breaching the skin barrier is thus essential for pathogens to enter the body. The skin contains various immune responsive cells that initiate both the innate and adaptive immune response upon invasion. Activated immune cells help to regulate cytokine response and their differentiation to promote or suppress the crucial immune response against invading pathogens. Human herpes simplex viruses (HHSVs) are the oldest pathogen that can escape immune surveillance of the human host by a well-developed escape mechanism within ganglia, as their evolutionary strategy. In primary infection, a non-specific defense of the host initiates the response against the invading virion. The initial direct antiviral action of the host is regulated by activated macrophages, via the release of cytokines like tumor necrosis factor (TNF), and type-1 interferon (IFN-1). The host-derived cytokines including IFN-12, TNF, and IFN-1 in turn induce natural killer (NK) cells to release IFN-γ. Their positive feedback with synergistic interactions collectively releases nitric oxide (NO) and reactive oxygen species (ROS) against the invading virus. Simultaneously, the combination of cytokines, macrophages, and other cells activates the immune system to eliminate the pathogen. However, the virus has also evolved various mechanisms to counter the host defense strategies. This review will highlight virus-mediated skin infections, especially by HSV, and portray a detailed role of virus-induced cytokines in host-immunity to challenge the invading virion during mucocutaneous HSV infection. Further, this review will discuss the viral-interference on host defense to provide a simplistic overview of the complications of cutaneous HSV infection.

Abstract Background The unifying hypothesis of competing endogenous RNA (ceRNA) wherein crosstalk between coding (mRNAs) and long non-coding RNAs (lncRNAs) via microRNA (miRNA) response elements, creates a pervasive regulatory network across the transcriptome, has been implicated in complex disorders including schizophrenia. Even with a wide range of high-throughput data, the etiology of schizophrenia remains elusive, necessitating a more holistic understanding of the altered genetic landscape, shifting focus from solely candidate gene studies and protein-coding variants. Objective We developed lncRNA-associated ceRNA networks to elucidate global molecular/regulatory signatures underlying schizophrenia using diverse data in the public domain. Methods Microarray dataset associated with peripheral blood mononuclear cells (PBMCs) of schizophrenia and control patients was used to identify differentially expressed mRNAs. Weighted gene co-expression network analysis (WGCNA) was used to identify highly correlated hubs, and genes from these overlapping Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) term genesets were considered key mRNA players. StarBase, Human MicroRNA Disease Database, and miRWalk were used to derive mRNA-miRNA and miRNA-lncRNA relationships. Finally, the key mRNAs, interacting lncRNAs and miRNAs were chosen to reconstruct sub-ceRNA networks based on network centrality scores. Results Bioinformatics analysis revealed the involvement of three differentially expressed mRNAs, namely ADRA1A, HAP1 and HOMER3 in the schizophrenia ceRNA networks with lncRNAs NEAT1, XIST, and KCNQ1OT1 modulating their activity by a suggestive sequestering of miR-3163, miR-214-3p and miR-2467-3p, respectively. Conclusions Furthermore, based on contextual evidence, we propose how ceRNAs could orchestrate crosstalk between neurostructural dynamics and immune/inflammatory processes and enable unifying these disparate models of schizophrenia etiology.

Abstract Hybrid 3D nanomaterials have been prepared by immobilizing the acid-functionalized MWCNTs into the edge-functionalized/oxidized Few Layer Graphene (FLG) flakes to address the dispersion and exfoliation of FLG flakes. Both acid-functionalized MWCNTs and the edge-oxidized FLG flakes were prepared in the laboratory. The acid-functionalized MWCNTs were prepared via oxidative treatment using a mixture of nitric acid (HNO3) and sulphuric acid (H2SO4). Fenton’s reaction was utilized for the preparation of the edge-oxidized FLG flakes using graphite flakes as the starting material. After the functionalization, the presence of the oxygen-containing functional groups was confirmed using FTIR spectroscopy and XPS spectroscopy. The thermal stabilities of the nanomaterials were compared using TGA thermogram and the 3D nanomaterial was observed to be more stable than any other nanoparticles that were prepared and reported in this paper. The surface morphology was observed using the SEM and TEM, and the immobilized functionalized MWCNTs between the edge functionalized FLG flakes were observed. The XRD spectra of the nanoparticles were also compared and Raman analyses have been carried out.

Interactions between various microbial pathogens including viruses, bacteria, fungi, oomycetes, and their plant hosts have traditionally been the focus of phytopathology. In recent years, a significant and growing interest in the study of eukaryotic microorganisms not classified among fungi or oomycetes has emerged. Many of these protists establish complex interactions with photosynthetic hosts, and understanding these interactions is crucial in understanding the dynamics of these parasites within traditional and emerging types of farming, including marine aquaculture. Many phytopathogenic protists are biotrophs with complex polyphasic life cycles, which makes them difficult or impossible to culture, a fact reflected in a wide gap in the availability of comprehensive genomic data when compared to fungal and oomycete plant pathogens. Furthermore, our ability to use available genomic resources for these protists is limited by the broad taxonomic distance that these organisms span, which makes comparisons with other genomic datasets difficult. The current rapid progress in genomics and computational tools for the prediction of protein functions and interactions is revolutionizing the landscape in plant pathology. This is also opening novel possibilities, specifically for a deeper understanding of protist effectors. Tools like AlphaFold2 enable structure-based function prediction of effector candidates with divergent protein sequences. In turn, this allows us to ask better biological questions and, coupled with innovative experimental strategies, will lead into a new era of effector research, especially for protists, to expand our knowledge on these elusive pathogens and their interactions with photosynthetic hosts. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract In quantum computing there are quite a few universal gate sets, each having their own characteristics. In this paper we study the Clifford+CS universal fault-tolerant gate set. The CS gate is used is many applications and this gate set is an important alternative to Clifford+T. We introduce a generating set in order to represent any unitary implementable by this gate set and with this we derive a bound on the CS-count of arbitrary multi-qubit unitaries. Analysing the channel representation of the generating set elements, we infer $${\mathcal {J}}_n^{CS}\subset {\mathcal {J}}_n^T$$ J n CS ⊂ J n T , where $${\mathcal {J}}_n^{CS}$$ J n CS and $${\mathcal {J}}_n^T$$ J n T are the set of unitaries exactly implementable by the Clifford+CS and Clifford+T gate sets, respectively. We develop CS-count optimal synthesis algorithms for both approximately and exactly implementable multi-qubit unitaries. With the help of these we derive a CS-count-optimal circuit for Toffoli, implying $${\mathcal {J}}_n^{Tof}={\mathcal {J}}_n^{CS}$$ J n Tof = J n CS , where $${\mathcal {J}}_n^{Tof}$$ J n Tof is the set of unitaries exactly implementable by the Clifford+Toffoli gate set. Such conclusions can have an important impact on resource estimates of quantum algorithms.

Abstract DNA binding transcription factors possess the ability to interact with lipid membranes to construct ion-permeable pathways. Herein, we present a thiazole-based DNA binding peptide mimic TBP2, which forms transmembrane ion channels, impacting cellular ion concentration and consequently stabilizing G-quadruplex DNA structures. TBP2 self-assembles into nanostructures, e.g., vesicles and nanofibers and facilitates the transportation of Na+ and K+ across lipid membranes with high conductance (~0.6 nS). Moreover, TBP2 exhibits increased fluorescence when incorporated into the membrane or in cellular nuclei. Monomeric TBP2 can enter the lipid membrane and localize to the nuclei of cancer cells. The coordinated process of time-dependent membrane or nuclear localization of TBP2, combined with elevated intracellular cation levels and direct G-quadruplex (G4) interaction, synergistically promotes formation and stability of G4 structures, triggering cancer cell death. This study introduces a platform to mimic and control intricate biological functions, leading to the discovery of innovative therapeutic approaches.

Introduction: The incidence of Acute Coronary Syndrome (ACS) in the young population has begun to rise. There is not enough data regarding the characteristics of young patients with ACS. Aim: To evaluate risk factors, clinical and angiographic profile of young patients with ACS. Materials and Methods: A prospective observational study was conducted from December 2017 to December 2020 at SSWH, Burdwan Medical College and Hospital, Burdwan, West Bengal, Kolkata, India among 100 patients. Patients with ACS and aged ≤45 years were enrolled in the study. Patients were divided into two groups: patients with and without obstructive Coronary Artery Disease (CAD). Clinical parameters and coronary angiography data were collected and analysed. The p-value

Abstract Background Tandem running is a recruitment method found in some species of ants where one ant follows another ant to reach a destination having maintained a physical contact with its antennae, throughout the journey. It is considered that the exchange of information regarding the destination among the nestmates happened during the process of tandem running. We examined the impact of restricting antennal movement on tandem running by using Diacamma indicum, a tandem-running ponerine ant by following 480 tandem runs across 9 treatment colonies and comparing it with 10 control relocating colonies. Result Though all the 19 colonies relocated successfully, treatment colonies took significantly longer time to do so. Restricted antennal movement did not influence the ability to become tandem leaders, initiate tandem runs or the work organization significantly. However, antennae-restricted ants performed fewer tandem runs and took significantly longer time. Followers with single or both antennae-restriction performed significantly higher number of interruptions and the alignment between the leader and follower was impacted as antenna-restricted followers subtended a greater angle and walked more to the side of the leader as compared to the control followers. Conclusion This study showed unhindered movement of the followers’ antennae is important for tandem-running ants. In the next step, to gain a comprehensive understanding of this recruitment method, it is essential to individually delineate different sensory modalities.

Abstract We have computed the superconformal partial wave for the mixed correlators involving J, $$\phi $$ ϕ , and $$\phi ^\dagger $$ ϕ † , where J is the superconformal primary of 4D $${{\mathcal {N}}} = 2$$ N = 2 stress-tensor multiplet, $$\phi $$ ϕ , and $$\phi ^\dagger $$ ϕ † are chiral and anti-chiral scalars, respectively in the channel $$\langle {J J}\phi \phi ^{\dagger }\rangle $$ ⟨ JJ ϕ ϕ † ⟩ . We have used the superembedding formalism and computed the conformal partial wave corresponding to the exchange of long multiplet using the supershadow approach. This study provides part of the ingredients necessary for the study of conformal bootstrap for mixed correlator in 4D $${{\mathcal {N}}} = 2$$ N = 2 superconformal field theories.

Abstract Background Renal cell carcinoma (RCC) was historically considered to be less responsive to radiation therapy (RT) compared to other cancer indications. However, advancements in precision high-dose radiation delivery through single-fraction and multi-fraction stereotactic ablative radiotherapy (SABR) have led to better outcomes and reduced treatment-related toxicities, sparking renewed interest in using RT to treat RCC. Moreover, numerous studies have revealed that certain therapeutic agents including chemotherapies can increase the sensitivity of tumors to RT, leading to a growing interest in combining these treatments. Here, we developed a rational combination of two radiosensitizers in a tumor-targeted liposomal formulation for augmenting RT in RCC. The objective of this study is to assess the efficacy of a tumor-targeted liposomal formulation combining the mTOR inhibitor everolimus (E) with the survivin inhibitor YM155 (Y) in enhancing the sensitivity of RCC tumors to radiation. Experimental design We slightly modified our previously published tumor-targeted liposomal formulation to develop a rational combination of E and Y in a single liposomal formulation (EY-L) and assessed its efficacy in RCC cell lines in vitro and in RCC tumors in vivo. We further investigated how well EY-L sensitizes RCC cell lines and tumors toward radiation and explored the underlying mechanism of radiosensitization. Results EY-L outperformed the corresponding single drug-loaded formulations E-L and Y-L in terms of containing primary tumor growth and improving survival in an immunocompetent syngeneic mouse model of RCC. EY-L also exhibited significantly higher sensitization of RCC cells towards radiation in vitro than E-L and Y-L. Additionally, EY-L sensitized RCC tumors towards radiation therapy in xenograft and murine RCC models. EY-L mediated induction of mitotic catastrophe via downregulation of multiple cell cycle checkpoints and DNA damage repair pathways could be responsible for the augmentation of radiation therapy. Conclusion Taken together, our study demonstrated the efficacy of a strategic combination therapy in sensitizing RCC to radiation therapy via inhibition of DNA damage repair and a substantial increase in mitotic catastrophe. This combination therapy may find its use in the augmentation of radiation therapy during the treatment of RCC patients.