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Nucleic acids derived from pathogens induce potent innate immune responses 1 – 6 . Cyclic GMP–AMP synthase (cGAS) is a double-stranded DNA sensor that catalyses the synthesis of the cyclic dinucleotide cyclic GMP–AMP, which mediates the induction of type I interferons through the STING–TBK1–IRF3 signalling axis 7 – 11 . cGAS was previously thought to not react with self DNA owing to its cytosolic localization 2 , 12 , 13 ; however, recent studies have shown that cGAS is localized mostly in the nucleus and has low activity as a result of tight nuclear tethering 14 – 18 . Here we show that cGAS binds to nucleosomes with nanomolar affinity and that nucleosome binding potently inhibits its catalytic activity. To elucidate the molecular basis of cGAS inactivation by nuclear tethering, we determined the structure of mouse cGAS bound to human nucleosome by cryo-electron microscopy. The structure shows that cGAS binds to a negatively charged acidic patch formed by histones H2A and H2B via its second DNA-binding site 19 . High-affinity nucleosome binding blocks double-stranded DNA binding and maintains cGAS in an inactive conformation. Mutations of cGAS that disrupt nucleosome binding alter cGAS-mediated signalling in cells. Structural studies show that cyclic GMP–AMP synthase binds to nucleosomes through its DNA-binding site, which maintains it in an inactive conformation and prevents self-DNA binding.

Microbial desalination cell (MDC) is a propitious technology towards water desalination by utilizing wastewater as an energy source. In this study, a multi-chambered MDC was used to bioremediate steel plant wastewater using the same wastewater as a fuel for anodic bacteria. A pure culture of Pseudomonas putida MTCC 1194 was isolated and inoculated to remove toxic phenol. Three different inoculum conditions, namely P. putida (INC-A), a mixture of P. putida and activated sludge (INC-B), and activated sludge alone (INC-C) were employed in an anodic chamber to mainly compare the electricity generation and phenol degradation in MDCs. The study revealed the maximum phenol removal of 82 ± 2.4%, total dissolved solids (TDS) removal of 68 ± 1.5%, and power generation of 10.2 mW/m2 using INC-B. The synergistic interactions between microorganisms, can enhance the toxic phenol degradation and also electricity generation in MDC for onsite wastewater application.

The Blockchain-Based Shipment Tracking System enhances supply chain management by leveraging blockchain technology to ensure transparency, security, and efficiency. Traditional supply chains often rely on outdated, paper-based systems, leading to scattered information, delays, and inefficiencies. Our system eliminates these challenges by providing a decentralized and real-time tracking solution where every update to a shipment’s status is securely recorded on the blockchain, ensuring all stakeholders have accurate and tamper-proof information. Built on the Ethereum blockchain, the system utilizes smart contracts written in Solidity to automate shipment tracking and management. It employs the Proof of Stake (PoS) consensus mechanism, which ensures efficient and secure transaction validation. To further enhance data security and integrity, SHA-256 hashing is applied to prevent unauthorized modifications. By integrating real-time tracking, immutable blockchain records, automated smart contract execution, and decentralized storage, the system reduces delays, minimizes fraud risks, and lowers operational costs. This innovative approach modernizes supply chain operations, making them more reliable, cost-effective, and resistant to disruptions, ultimately transforming logistics and transportation industries.

Clostridioides difficile secretes Toxin B (TcdB) as one of its major virulence factors, which binds to intestinal epithelial and subepithelial receptors, including frizzled proteins and chondroitin sulfate proteoglycan 4 (CSPG4). Here, we present cryo-EM structures of full-length TcdB in complex with the CSPG4 domain 1 fragment (D1 401-560 ) at cytosolic pH and the cysteine-rich domain of frizzled-2 (CRD2) at both cytosolic and acidic pHs. CSPG4 specifically binds to the autoprocessing and delivery domains of TcdB via networks of salt bridges, hydrophobic and aromatic/proline interactions, which are disrupted upon acidification eventually leading to CSPG4 drastically dissociating from TcdB. In contrast, FZD2 moderately dissociates from TcdB under acidic pH, most likely due to its partial unfolding. These results reveal structural dynamics of TcdB during its preentry step upon endosomal acidification, which provide a basis for developing therapeutics against C . difficile infections.

Purpose In the present research, the potential of reactivated consortium for the methane production consuming waste coal as a carbon source (1% w/v) in the modified media at mesophilic temperature (37 °C) was determined. Methods Media modification was conducted for the enhancement of methane production by selecting three different components from the two media, i.e., Methanosprillium sp. producing media (MSP) and methane-producing bacteria media (MPB). From MSP medium, C 2 H 2 NaO 2 (sodium acetate), KH 2 PO 4 (potassium dihydrogen the phosphate), and NaHCO 3 (sodium bicarbonate) whereas from MPB medium; yeast extract, peptone, and NH 4 Cl (ammonium chloride) were selected in the range of 0.5–2.5 (g/l). Analytical assay, i.e., Fourier transform infrared spectroscopy (FTIR), gas chromatography mass spectrophotometry (GCMS), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) were conducted. Further, compatibility study and pathogenicity was performed. Results In the present study, reactivated consortia was used therefore key components of the media were modified. In case of MPB medium, 2 g/l of yeast extract, 2 g/l peptone, and 1 g/l NH 4 Cl showed the promising results; whereas for MSP medium, 1 g/l of KH 2 PO 4 , 0.5 g/l of NaHCO 3 , and 1.5 g/l of C 2 H 2 NaO 2 were noted to be the suitable range for methane production. Analytical studies confirmed the presences of -OH and aliphatic groups which majorly belongs to alkane, alkene, and phenol derivative compounds whereas SEM and EDX studies delineated the active interaction of bacteria with coal particles and presences of carbon (C) as a major peak in untreated coal and absence of C peak in microbial treated coal. In addition, a compatibility study was performed and their successful results aid in the future approach of field implementation. Further, pathogenicity data indicated the non-virulent and non-toxic nature of the consortia. Conclusions The production of waste coal is one of the most problematic and common activities of the mining industry. They release toxic substances into the environment (water, air, and soil) and damage the local biodiversity. Therefore, the generation of biogenic methane from waste coal is an environmentally friendly approach to overcome this problem.

The present descriptive research focused on determining the traits of patients who required endodontic treatment during the COVID-19 lockdown and various stages of unlocking in Mumbai metropolitan region. The descriptive analysis was carried out by examining the patients who were registered at Nair Hospital Dental College, Mumbai during four phases of lockdown (25 March to 31 May 2020) and eight phases of unlock (1 June 2020 to 31 January 2021). The evaluation was performed by evaluating the number of days and the overall number of patients reported for endodontic treatment for the first and subsequent visits. Each patient underwent intensive triage, which included taking their body temperature, oxygen saturation level, and travel history. The sex, age, and endodontic diagnosis of the offending tooth were also reported. The pain parameters were analyzed using a verbal numerical rating score (VNRS). During the lockdown phases, 297 patients seeking endodontic treatment visited the hospital over a total of 26 working days, and during the unlock phases, 16,195 patients visited the hospital over 189 working days. The average age of the patients that visited were 31–40 years of age (57.23%). The mean VNRS score was 5.85 ± 1.62. For both the lockdown and unlock periods, a significantly higher percentage of males visited dental school (p < 0.001). When compared to other stages, the number of patients attending during lockdown phase 4 (55.56%) and unlock phase 8 (32.35%) was the highest. The majority of endodontic emergency diagnoses were reversible pulpitis (36.5%) and symptomatic irreversible pulpitis (33.14%), all of which had higher mean VNRS (p < 0.05). Of the 49 patients that reported with COVID-19 symptoms, 11 tested positive. During the lockdown and unlock periods, 12 of the 41 treating workers tested positive. Personal protective equipment and patient screening are critical in shielding clinicians during the COVID-19 pandemic.

COVID-19 has had a new challenge on dental workers, radically altering clinical and personal management. The cross-sectional survey sought to examine and comprehend the influence of COVID-19 on Indian dentistry practitioners. A 38-item questionnaire-based survey was communicated to Indian dental practitioners through a web-based form (Google form). The questionnaire was categorized into four sections: (i) Personal protective equipment (PPE), (ii) dental treatments, (iii) auxiliary management, and (iv) personal impact. The findings were examined and studied in order to comprehend the repercussions of COVID-19. The questionnaire was completed by 513 of the 1129 dentists to whom it was delivered. For the current questionnaire, a response rate that we received was 45.44%. When compared to the pre-pandemic era, the use of PPE has increased dramatically (95.7%). The use of PPE alleviated dental practitioners' and patients' doubts about viral transmission. The epidemic prompted the Ministry of Health and Family Welfare (MoHFW) to issue specific recommendations for dental treatments, which were followed by 92.5% of dentists. The majority of dentists reported a considerable impact on both financial and mental health concerns. Teleconsulting and distant learning gained greater prominence. The COVID-19 epidemic affected the lives of dental professionals both within and outside of the dental setting, as well as the auxiliary. COVID-19 has left a trail of devastation in its aftermath. Dentists were affected both emotionally and professionally. Dentists rapidly and uniformly followed the revised recommendations.

A new technology called microbial desalination cell (MDC) approaches a comprehensive way to design an innovative system for removal of organic matter and dissolved solids from wastewater. In this study, two laboratory scale MDCs having three chambered (3C-MDC) and five chambered (5C-MDC) configuration were developed for integrated biodegradation of steel plant wastewater. The 3C-MDC have anodic, middle desalination and cathodic chamber; while 5C-MDC have anodic, cathodic, middle desalination and two concentrate chambers separated by ion exchange membranes. Using synthetic saline water with 8 and 30 g/L of TDS and steel plant wastewater (3.74 g TDS/L) in desalination chamber, the TDS removal of 64 ± 2.3%, 75 ± 1.8%, and 58 ± 1.3% were observed in 3C-MDC, while in 5C-MDC, those were 58 ± 1.5%, 71 ± 2.1%, and 64 ± 2.4%, respectively in 96 h of fed batch operation. With 30 g/L of TDS concentration, the power generation observed in 3C-MDC and 5C-MDCs were (81 mW/m2 and 78 mW/m2) higher than the power observed with 8 g/L (56 mW/m2 and 45 mW/m2). However, with steel plant wastewater in desalination chamber the power density increased to 76 mW/m2 in 5C-MDC and significantly decreased to 39 mW/m2 in 3C-MDC.

Thymidylate kinase (TMK) is a pivotal enzyme in Mycobacterium tuberculosis (Mtb), crucial for phosphorylating thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), thereby playing a critical role in DNA biosynthesis. Dysregulation or inhibition of TMK activity disrupts DNA replication and cell division, making it an attractive target for anti-tuberculosis drug development. In this study, the statistically validated pharmacophore mode was developed from a set of known TMK inhibitors. Further, the robust pharmacophore was considered for screening the Enamine database. The chemical space was reduced through multiple molecular docking approaches, pharmacokinetics, and absolute binding energy estimation. Two different molecular docking algorithms favor the strong binding affinity of the proposed molecules towards TMK. Machine learning-based absolute binding energy also showed the potentiality of the proposed molecules. The binding interactions analysis exposed the strong binding affinity between the proposed molecules and active site amino residues of TMK. Several statistical parameters from all atoms MD simulation explained the stability between proposed molecules and TMK in the dynamic states. The MM-GBSA approach also found a strong binding affinity for each proposed molecule. Therefore, the proposed molecules might be crucial TMK inhibitors for managing Mtb inhibition subjected to in vitro/in vivo validations.