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Glioblastomas (GBMs) are characterized as highly invasive; the contribution of GBM stem-like cells (GSCs) to the invasive phenotype, however, has not been completely defined. Towards this end, we have defined the invasion potential of CD133+ GSCs and their differentiated CD133- counterparts grown under standard in vitro conditions and in co-culture with astrocytes. Using a trans-well assay, astrocytes or astrocyte conditioned media in the bottom chamber significantly increased the invasion of GSCs yet had no effect on CD133- cells. In addition, a monolayer invasion assay showed that the GSCs invaded farther into an astrocyte monolayer than their differentiated progeny. Gene expression profiles were generated from two GSC lines grown in trans-well culture with astrocytes in the bottom chamber or directly in contact with astrocyte monolayers. In each co-culture model, genes whose expression was commonly increased in both GSC lines involved cell movement and included a number of genes that have been previously associated with tumor cell invasion. Similar gene expression modifications were not detected in CD133- cells co-cultured under the same conditions with astrocytes. Finally, evaluation of the secretome of astrocytes grown in monolayer identified a number of chemokines and cytokines associated with tumor cell invasion. These data suggest that astrocytes enhance the invasion of CD133+ GSCs and provide additional support for a critical role of brain microenvironment in the regulation of GBM biology.

Background: Illness behaviour refers to any actions or reactions of an individual who feels unwell for defining their state of health and obtaining physical or emotional relief from perceived or actual illness. The present study was conducted to assess illness perception of patients having dental caries using Illness Perceptions Questionnaire-Revised (IPQ-R) in Odisha., Materials and Methods: A descriptive co-relational study was conducted among 250 patients with self-reported dental caries in at least one tooth and more than 18 years of age. Data was collected using a cross-culturallyvalidated IPQ-R tool. This was followed by assessment for dental caries using Caries Severity Index. Spearman's correlation and multivariable analysis were conducted., Results: Toothache, visible hole, tooth sensitivity, pain during taking hot and cold food were perceived to be associated with dental caries. Nearly half of the patients had a caries severity score of 5 (pulpitis) or more. Majority (83 %) of participants reported presence of a "visible hole" when they had dental caries. Caries severity was positively correlated with timeline acute/chronic, timeline cyclical and consequence. Significant correlations were noted between IPQ-R components as well., Conclusion: Dental caries was mostly considered to be acute in nature. The study subjects perceived dental caries to have serious consequence, emotionally disturbing symptoms, which they could control by seeking treatment. Further studies need to be conductedwith a larger sample size., 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., (© 2025 The Authors.)

We report the syntheses, spectroscopic analyses, and solid-state structural evidence of a quasi-planar aromatic [38] E -ethylene bridged octaphyrin (1.2.1.0.1.2.1.0) exhibiting NIR absorption. The chemical oxidation using an appropriate oxidant led to unique π reconstruction via amine-imine conversion and/or C-oxygenation of the inverted thiophene rings resulting in weakly antiaromatic or nonaromatic [36] octaphyrins with preserved E -conformation of the ethylene moieties. The aromatic nature of the studied octaphyrins is supported by GIMIC calculations of the magnetically induced ring current density.

Retrosynthetically designed and syntheses of three unprecedented core modified N-confused porphyrinoids exhibiting vis-NIR absorption with tunable aromaticity is reported. Controlled modification of types of oxidants (chloranil vs. DDQ) has led to the isolation of 18π-aromatic porphyrinoid 7 (upon chloranil oxidation) while DDQ oxidation has led to 18 e σ-aromatic porphyrinoids 8 and 9. All the three SN3 hybrid N-confused porphyrinoids 7-9 have been thoroughly characterized via solution state spectroscopic measurements and in-depth DFT studies for concluding π-aromaticity of 7 and σ-aromaticity of 8 and 9. While 7 could recognize the fluoride anion with high selectivity via deprotonation rather than an anion recognition based mechanism, acetate anion binding studies clearly revealed NH⋅⋅⋅AcO - H-bonding interaction in the host-guest complex [7-AcO - ] supporting an anion recognition based mechanism. Porphyrinoids 8 and 9 remain unsusceptible to anion recognition. The conformational preorganization and anion induced deprotonation leading to conformational reorganization have been extensively studied by solution state spectroscopic techniques and in depth DFT level theoretical calculations., (© 2024 Wiley-VCH GmbH.)

Context: Tobacco addiction is an important public health problem. Among several theories of addiction proposed, PRIME theory of motivation is found to be a comprehensive one to synthesise prevention strategies., Aims: This case study was conducted on the basis of PRIME theory to explain smokeless tobacco (SLT) addiction patterns among slum dwelling female residents of Cuttack district, Odisha., Settings and Design: Cuttack district of Odisha state and Qualitative synthesis., Methods and Material: Qualitative semistructured face-to-face interviews and framework analysis techniques were employed. The study was conducted over a period of 2 months between February 2020 and March 2020. Face-to-face interviews of 26 participants of Dasha Sahi slum using a semistructured questionnaire assessing responses based on five main themes including P, Plans; R, Responses; I, Impulses And Inhibitory Forces; M, Motives; and E, Evaluations of the said theory., Statistical Analysis Used: Verbatim transcripts were analysed using thematic framework analysis., Results: A majority of the participants were multiple SLT product users, and they did not have an immediate plan to quit. Most of the participants showed strong emotional attachment with these products and considered them the only source of pleasure (want) in a life full of miseries. The words "Tobacco" and "Nicotine" were medical jargons for them. Though they were aware of the harmful effects, they had a positive evaluative belief about its use because of cognitive dissonance. Most of them were habitual users living in an environment full of physical and social cues., Conclusions: This case study is well in line with the PRIME theory in explaining the addictive behaviour; a comprehensive multi-strategic approach was formulated for inculcating quitting behaviour among this disadvantaged section of the population as suggested by the proposer of this theory., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Synthesis, spectroscopic and theoretical characterization of a hitherto unknown meso - meso N-confused N -methylpyrrole-bridged doubly N-confused hexaphyrin (molecule 5) and its organometallic copper(II) complex (molecule 6) are reported herein. The absence of Q-type bands in the UV-Vis spectrum and the high chemical shifts of the inner proton signals of 5 suggest its globally non-aromaticity. The spectroscopic evidence of non-aromaticity for 5 and the paramagnetic nature of 6, are fully supported by density functional theory (DFT) calculations of the UV-Vis spectra, electron paramagnetic resonance (EPR) g -tensor parameters, and the magnetically induced current density strengths obtained with the gauge-including magnetically induced currents (GIMIC) method.

Retrosynthetic design and synthesis with structural isolation of two unprecedented core modified N-confused N-fused porphodimethene-like porphyrinoids possessing a [5.5.5.5] tetracyclic ring with tunable photophysical properties is reported. The solid-state X-ray crystal structure reveals the expected cis geometry for the meso -sp 3 carbons. Controlled chemical oxidation of the porphodimethene analogue 11 bearing the N-confused pyrrole moiety to the corresponding porphotrimethene 12 has been achieved in quantitative yield, while 10 bearing the N -methyl N-confused pyrrole moiety remained unsusceptible to chemical oxidation. All three S2N3 hybrid N-confused N-fused porphodi(tri)methene-like porphyrinoids 10-12 could recognize the fluoride anion with high selectivity; however, porphodimethene 10 and porphotrimethene 12 do so via deprotonation rather than an anion recognition based mechanism as has been anticipated in the case of porphodimethene 11.

Background: The presence of dental caries may have a negative impact on well-being of children and their parents, causing pain and discomfort, leading to poor oral health-related quality of life (OHRQoL) in them. The objective of this study was to evaluate the impact of different levels of caries experience on the OHRQoL of pre-school children and their families in Odisha, assessed using Odia version of Early Childhood Oral Health Impact Scale (Od-ECOHIS)., Methodology: A cross-sectional survey was carried out on a sample of 369 pre-school children using Od-ECOHIS. Dental caries was recorded using International Caries Detection and Assessment System (ICDAS) index., Result: The total score of ECOHIS ranged from 0 to 42 with a mean of 2.4 (±5.3) and a median score of 0. The items bearing high mean scores in the child impact section were related to "pain", "difficulty in drinking hot or cold beverages", "difficulty in eating some food", and "irritable or frustrated". Though half of children (50.4%) had cavitated carious lesions, the prevalence of negative impact was 30.6%. Compared to the child being caries-free, the expected count of total Od-ECOHIS score increased by 1.54 times if the child had white spot lesion and 1.94 times if the child had a cavitated lesion., Conclusion: Presence of dental carious lesions has a significant impact on OHRQoL of pre-school children and their families measured by using Od-ECOHIS even after adjusting for SES and caregivers' perception of their children's oral health., (Copyright © 2024 Copyright: © 2024 Indian Journal of Dental Research.)

Objective: To investigate patients' preference for extraction or preservation for toothache and hypothetical anterior tooth pain along with the specific reason for their choice., Basic Research Design: Cross-sectional analytical semi-structured interview study., Participants: A sample of 703 adult dental outpatients visiting secondary and tertiary government health centres with toothache due to dental caries in Eastern India., Main Outcome Measures: Patients preferring restorative or extraction services for toothache, specific reason, and socio-demographic background factors for anterior and posterior teeth., Results: Half (50.1%) choose preservation for present toothache and 79.9% for hypothetical front tooth pain. Immediate relief from toothache for extraction and the motive to preserve natural teeth for preservation were the main reasons expressed. In logistic regression, participants preferring extraction were more likely to be aged 25-34 years (OR = 1.94), 55+ years (OR=33.32), have primary and below education level (OR=1.99), have had a previous extraction (OR=1.99) and be unaware of preservation options (OR=2.34). For assumed anterior tooth pain, those between 25-34 years (OR=0.39) were more likely to choose preservation. Participants with primary and below education levels (OR=1.99) and unaware of preservation options (OR=1.95) chose extraction of the front tooth irrespective of their choice of treatment for the present toothache., Conclusion: Notable differences between the choices to preserve or extract a posterior tooth were not found. There was greater preference towards preserving anterior teeth. Future research should identify additional barriers to the preference and utilization of restorative services., (Copyright© 2024 Dennis Barber Ltd.)

Purpose: To determine if video-based educational intervention compared to the standard verbal guidelines, provided to caregivers on home-based palliative care could enhance the quality of life (QoL) in advanced head and neck cancer (HNC) patients., Methods: The study employed a prospective, two-arm parallel-group, randomized controlled trial design. Investigators prepared a real-world demonstrational video of ten minutes duration regarding home-based care for family caregivers, with voice-over in Odia language (Eastern India). The contents of the video addressed the management of common problems in palliative care among HNC patients. This study included 180 participants, 90 patient & caregiver dyads randomized to interventional (video-based education) or control (verbal instruction) groups. Patients' QoL was measured at baseline and 3 weeks follow-up using EORTC QLQ C30. Data were analyzed descriptively, and the Chi-square, Mann-Whitney U, T-test, spearman correlation, and multiple hierarchical regression analyses were employed for statistical analysis, with a significance level of p < 0.05., Results: Seventy participant dyads completed the planned two assessments: baseline and at the end of 3rd week (Intervention = 37; Control = 33). The intervention group showed a significant improvement in the patient's health-related QoL, physical, emotional, and social functioning. Symptom burden reduction was observed for pain, nausea, and fatigue. A significant increase in the change in QoL with the video-based education group (VBE) compared to the verbal instruction (VI) group after adjusting for age, gender, physical functioning, and pain symptomology (adjusted R 2  = 0.402) was noted., Conclusion: VBE intervention using smart-phone may offer caregivers a viable means of enhancing self-management while improving patients' QoL within the socio-cultural challenges for home-based palliative care in India. Further research on training caregivers using digital interventions and home-based visits is recommended., Trial Registration Number: CTRI/2021/06/034473 [Registered on: 30/06/2021]., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Judicious syntheses, spectroscopic analyses, and solid state structural evidence of two structural variants (with planar geometry) of strongly aromatic hybrid [30] E -ethylene bridged hexaphyrins (2.1.1.2.1.1) exhibiting strong NIR absorption are reported. The induced correspondence of fused phenanthrene on the pyrrole moieties has led to a further red-shift of up to ∼45 nm in the neutral and protonated form of the macrocycles. The electronic nature and aromaticity of both hexaphyrins are fully supported by DFT calculations.

Background: Dentists are often overlooked resources in the workforce for disaster management (DM). To determine the knowledge, attitudes, willingness, and self-perceived effectiveness to participate in DM among general dental practitioners (GDPs) of Eastern India., Materials and Methods: A web-based online survey was conducted among 256 Dental Council of India registered GDPs of Cuttack district, Odisha. The 45-item survey comprised closed-ended questions on the demographic data of the participants, years of practice, previous experience in DM, and willingness to participate. Other domains assessed were the participants' objective knowledge of DM, attitude, and self-perceived effectiveness toward participation during disasters. Data were analyzed descriptively, and the Chi-square and Mann-Whitney U tests were used for statistical analysis, with a significance threshold of P < 0.05., Result: A total of 154 responses were analyzed, giving a response rate of 60.16%. The average age was ≤35 years, 59.1% were BDS dentists and 78.6% had less than 10 years of practice. Only 18% of them had previous experience with DM, and merely 3.2% were formerly trained; however, 95.5% of the dentists were willing to participate in DM. The mean DM knowledge and attitude scores were 16.12 (CI = 15.4-16.8) and 5.79 (5.45-6.13), respectively. Knowledge and attitude showed a significant correlation. About 56% indicated that they would be able to respond effectively to a disastrous event. Significant associations were observed between age group ( P = 0.008), years of clinical practice ( P = 0.001), qualification ( P = 0.012), previous participation ( P = 0.029), and self-perceived effectiveness., Conclusion: The knowledge regarding DM among respondents was at an average level. However, the majority of them were found to have a positive attitude toward participation in DM. Thus, including DM in dental curricula and drills for dental professionals might prove beneficial as almost all GDPs were showing greater self-perceived effectiveness and willingness to participate in disasters., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Education and Health Promotion.)

Research on eyewitness identification often involves exposing participants to a simulated crime and later testing memory using a lineup. We conducted a systematic review showing that pre-event instructions, instructions given before event exposure, are rarely reported and those that are reported vary in the extent to which they warn participants about the nature of the event or tasks. At odds with the experience of actual witnesses, some studies use pre-event instructions explicitly warning participants of the upcoming crime and lineup task. Both the basic and applied literature provide reason to believe that pre-event instructions may affect eyewitness identification performance. In the current experiment, we tested the impact of pre-event instructions on lineup identification decisions and confidence. Participants received non-specific pre-event instructions (i.e., "watch this video") or eyewitness pre-event instructions (i.e., "watch this crime video, you'll complete a lineup later") and completed a culprit-absent or -present lineup. We found no support for the hypothesis that participants who receive eyewitness pre-event instructions have higher discriminability than participants who receive non-specific pre-event instructions. Additionally, confidence-accuracy calibration was not significantly different between conditions. However, participants in the eyewitness condition were more likely to see the event as a crime and to make an identification than participants in the non-specific condition. Implications for conducting and interpreting eyewitness identification research and the basic research on instructions and attention are discussed., (© 2023. The Author(s).)

Objective: The aim of the study is to provide a systematic review of the potential evidence for the effect of platelet rich fibrin (PRF) on stability of dental implants., Methods: A systematic review was performed based on the Preferred Reporting Items for Systematic review and Meta-analysis. An extensive and comprehensive electronic search was carried out from January 2000 to March 2021, independently by author in PUBMED, Cochrane Central Register of Controlled Trials, Google Scholar, Scopus, Embase, and Web of Science irrespective of publication status, date, or language. For any registered ongoing or completed but unpublished trial, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and Cochrane Oral Health's Trials Register websites were searched. Randomized, controlled, and clinical trials which assessed the stability of implant with and without use of PRF using Osstell device by radiofrequency analysis were selected., Results: The electronic and manual search yielded 630 studies. In all the eight included studies implant stability was measured using same ISQ units by Osstell device. Meta-analysis was carried out in six studies that had similar comparisons and reported the same outcomes at same time interval. Random effect models have shown pooled mean difference of 4.49 (95% CI 1.22-7.76) for 1-week post-insertion, 3.65 (95% CI 2.21-5.09) for 4-week post insertion, 3.25 (95% CI 0.03-6.47) for 8-week post-insertion, and 2.79 with 95% CI of 0.48, 5.10 for 12-week post-insertion., Conclusions: The present systematic review suggests that PRF is effective in improving secondary implant stability with certain limitations and displays possible implication for clinical practice., (Copyright: © International Journal of Health Sciences.)

Structural isolation of two unprecedented AIEE/ACQ type fluorophores based on N -methyl N-confused tripyrromonomethene analogues exhibiting selective F - anion-coordination-induced-enhanced emission (ACIEE) with a detection limit of 10 -7 M is reported. The intrinsic relation between molecular structures/molecular arrangements with (without) anion binding have been revealed at a deeper level via spectroscopic measurements and DFT level theoretical studies.

Rational design and isolation of two hitherto unknown highly stable single conformer of ferrocene incorporated meso-aryl substituted singly N-methyl N-confused-calixphyrins have been achieved in quantitative yields. The solid-state crystal structure reveals the obvious trans-geometry for the meso-protons with the possibility for both the macrocycles to exist either racemic or enantiomer forms. However, thorough solution-state spectroscopic characterization strongly concludes the experimental isolation of a single isomer for both the macrocycles. The drastic modification of UV-vis spectral patterns upon imine pyrrole N protonation and amine pyrrole NH deprotonation of both the calixphyrins could pave way for these macrocycles to act as opto-electronic materials. The conformational preorganization and protonation and deprotonation induced conformational reorganization have been extensively studied by solution state spectroscopic techniques, solid state X-ray crystal structure and in depth DFT level theoretical calculations., (© 2022 Wiley-VCH GmbH.)

The highlight of this article is the recent progress in the state-of-the-art synthetic design and isolation of artificial porphyrinoids by swapping pyrrole component(s) with diverse functionalized pyrrolic(heterocyclic)/carbacycle building block(s) to compare the impact on the electronic absorption spectra and aromaticity of the incorporated isomeric/expanded porphyrinoids. Attention has been directed towards five distinct criteria of utilizing functionalized pyrrolic(heterocyclic)/aromatic hydrocarbons as synthons for NIR absorbing aromatic isomeric (N-confusion)/expanded porphyrinoids (with five/six heterocycles): (i) fused or annelated pyrrole (heterocycle), (ii) functionalized bi-pyrrole/bi-thiophene/bi-furan building blocks, (iii) azulene based carbacycle building block, (iv) vinylogous aromatic carbacycle/heterocycle(s) building block and (v) N-confused pyrrole ring(s), and N-confused fused pyrrole ring(s) leading to π-extension. These hybrid porphyrinoids are ideal candidates for basic research into macrocyclic aromaticity and for many potential applications owing to NIR absorption.

Concise syntheses and spectroscopic, solid state X-ray crystal structure and theoretical studies of three electronically appealing new generation hitherto unknown ferrocenyl bridged N-confused heterocyclic macrocycles with (without) fusion are reported. Intriguingly, the expanded N-confused fused phlorin (1.1.1.1.1) with the built-in tripentacyclic [5.5.5] moiety exhibits tailing of the NIR absorption band beyond 1000 nm while the nonconjugated porphodimethene and a new generation π-extended isomeric corrorin analogue exhibit UV-vis absorption.

Aim and Objective: Traumatic dental injury (TDI) is a significant public health concern. This study aimed to perform a systematic review on the prevalence, trends, and possible risk factors of dental trauma in permanent teeth among children and adolescents in India., Materials and Methods: Literature search was carried out, in PubMed, EMBASE, Web of Science, Cochrane, Google scholar, and Gray literature (MDS dissertation, manuscripts) database up to October 5, 2020, reporting on dental trauma prevalence in India. Meta-analyses were done using random effects model. Pooled estimates were calculated with a confidence interval of 95% (95% CI) both for prevalence and odds ratios (OR). Trend analysis was performed for the included studies. Quality assessment of the included studies was done using the Hoy checklist for prevalence studies. Qualitative synthesis was done for predictors in which meta-analysis could not be performed., Results: This online searching strategy collected and listed 2,491 articles on this topic. After evaluating their titles and abstracts, only 59 were finally selected for complete review and data collection. All studies had been performed in children and adolescents. The pooled prevalence of dental trauma in permanent teeth was 11%. Positive summary association of dental trauma with male gender (pooled OR = 1.52; 95% CI: 1.37-1.70), inadequate lip coverage (pooled OR = 4.76; 95% CI: 3.18-7.11), and increased overjet of >3.5mm (pooled OR = 4.84; 95% CI: 2.86-8.19) and >5.5 mm (pooled OR = 4.93; 95% CI: 4.32-5.63) was observed. Prevalence of dental trauma showed an increasing trend with time. All of the studies were having moderate-high risk of bias., Conclusion: Approximately 9-13% of the children and adolescents in India presented some type of TDI in permanent teeth, with an increasing trend. Boys, children, and adolescents presenting inadequate lip coverage, or an increased overjet greater than 3.5 and 5.5 mm are more likely to have traumatic dental injuries., Clinical Significance: Future population-based analytical studies on TDI in India are recommended.

Expedient synthesis, spectroscopic, solid state structural proof, and theoretical study of helically twisted weakly aromatic hybrid singly N-confused ferrocenoporphyrinoids and the peripheral coordinated Rh(I) complex are reported. The X-ray crystal structure of the macrocycles reveals an ambiguously inverted pyrrole ring reinforcing regioselective β,β-linkage with the spatially adjacent N-confused N -methyl pyrrole ring leading to endocyclic extension of macrocyclic π-conjugation via tricyclic [5.5.5] moiety. The three-dimensional structure with built-in fused tricyclic [5.5.5] moiety has paved way to three-dimensional weak diatropicity with vis-NIR absorptions. The peripheral coordinated Rh(I) complex owing to helical chirality about the macrocyclic ring and planar chirality about the square planar Rh coordination site exists as a mixture of diastereomers (5:3) with well resolved 1 H NMR spectra anticipating weak aromaticity. The experimental spectroscopic measurements are in agreement with theoretically determined electronic structure and properties strongly elucidating sustained weak diatropic ring currents in twisted macrocycles both in neutral form and in the metalated complex. Further fragment molecular orbital approach and molecular orbital theory gave insights on the stability of N-confused β-β fused oxo-ferrocenoporphyrinoids and formation of the selective peripheral coordinated Rh(I) complex.

The widely conserved twin-arginine translocases (Tat) allow the transport of fully folded cofactor-containing proteins across biological membranes. In doing so, these translocases serve different biological functions ranging from energy conversion to cell division. In the Gram-positive soil bacterium Bacillus subtilis, the Tat machinery is essential for effective growth in media lacking iron or NaCl. It was previously shown that this phenomenon relates to the Tat-dependent export of the heme-containing peroxidase EfeB, which converts Fe 2+ to Fe 3+ at the expense of hydrogen peroxide. However, the reasons why the majority of tat mutant bacteria perish upon dilution in NaCl-deprived medium and how, after several hours, a sub-population adapts to this condition was unknown. Here we show that, upon growth in the absence of NaCl, the bacteria face two major problems, namely severe oxidative stress at the membrane and starvation leading to death. The tat mutant cells can overcome these challenges if they are fed with arginine, which implies that severe arginine depletion is a major cause of death and resumed arginine synthesis permits their survival. Altogether, our findings show that the Tat system of B. subtilis is needed to preclude severe oxidative stress and starvation upon sudden drops in the environmental Na + concentration as caused by flooding or rain., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

In order to adjust to changing environmental conditions, bacteria use nucleotide second messengers to transduce external signals and translate them into a specific cellular response. Cyclic di-adenosine monophosphate (c-di-AMP) is the only known essential nucleotide second messenger. In addition to the well-established role of this second messenger in the control of potassium homeostasis, we observed that glutamate is as toxic as potassium for a c-di-AMP-free strain of the Gram-positive model bacterium Bacillus subtilis. In this work, we isolated suppressor mutants that allow growth of a c-di-AMP-free strain under these toxic conditions. Characterization of glutamate resistant suppressors revealed that they contain pairs of mutations, in most cases affecting glutamate and potassium homeostasis. Among these mutations, several independent mutations affected a novel glutamate transporter, AimA (Amino acid importer A, formerly YbeC). This protein is the major transporter for glutamate and serine in B. subtilis. Unexpectedly, some of the isolated suppressor mutants could suppress glutamate toxicity by a combination of mutations that affect phospholipid biosynthesis and a specific gain-of-function mutation of a mechanosensitive channel of small conductance (YfkC) resulting in the acquisition of a device for glutamate export. Cultivation of the c-di-AMP-free strain on complex medium was an even greater challenge because the amounts of potassium, glutamate, and other osmolytes are substantially higher than in minimal medium. Suppressor mutants viable on complex medium could only be isolated under anaerobic conditions if one of the two c-di-AMP receptor proteins, DarA or DarB, was absent. Also on complex medium, potassium and osmolyte toxicity are the major bottlenecks for the growth of B. subtilis in the absence of c-di-AMP. Our results indicate that the essentiality of c-di-AMP in B. subtilis is caused by the global impact of the second messenger nucleotide on different aspects of cellular physiology., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Radiation-induced oral mucositis (RIOM) is considered the most severe non-haematological complication affecting almost every head and neck cancer patient during the course of radiotherapy (RT). Curcumin, a herbal agent present in Indian spice 'Turmeric' has anti-inflammatory, immunomodulation and wound healing properties. The objective of this pilot randomised controlled clinical trial was to compare the effectiveness and safety of 0.1% curcumin (freshly prepared using nanoparticles) and 0.15% benzydamine mouthwash on RIOM among 74 head and neck cancer patients scheduled to receive RT., Materials and Methods: Assessment of RIOM was carried out using WHO criteria once in a week for 6 weeks. Both modified intention to treat (MIT) and per protocol (PP) analysis were carried out to test the null hypothesis of equal effectiveness on prevention and severity of RIOM., Results: As far as the onset of RIOM is concerned, MIT analysis showed that the instantaneous risk of getting the onset of RIOM was 50% lower (hazard ratio 0.5) in curcumin. Onset of RIOM was also significantly delayed (mean = 19.56, median = 21) in the test group by 2 weeks. But in 'PP' analysis, no significant difference was observed between two preparations and almost all patients experienced the onset. Both the mouthwashes were equally effective in preventing the occurrence of severe form of RIOM in PP analysis after dichotomisation of severity score (≥3 and ≤2)., Conclusion: Though both the mouthwashes were not able to completely prevent the onset of RIOM and reduce the severity of RIOM, use of 0.1% curcumin mouthwash was able to significantly delay the onset of RIOM (Clinical trial registration no. CTRI/2018/04/013362)., Competing Interests: None

High yield synthesis and spectroscopic isolation of two hitherto unknown highly stable single conformers of meso-aryl substituted dithia/diselena trans-doubly N-confused porphyrins with fully π-conjugated [18] annulene structures are reported. In-depth solution state spectroscopic measurements and DFT level theoretical calculations strongly show the distinct aromaticity with strong NIR absorption of these new macrocycles.

The Gram-positive bacterium Bacillus subtilis is frequently exposed to hyperosmotic conditions. In addition to the induction of genes involved in the accumulation of compatible solutes, high salinity exerts widespread effects on B. subtilis physiology, including changes in cell wall metabolism, induction of an iron limitation response, reduced motility and suppression of sporulation. We performed a combined whole-transcriptome and proteome analysis of B. subtilis 168 cells continuously cultivated at low or high (1.2 M NaCl) salinity. Our study revealed significant changes in the expression of more than one-fourth of the protein-coding genes and of numerous non-coding RNAs. New aspects in understanding the impact of high salinity on B. subtilis include a sustained low-level induction of the SigB-dependent general stress response and strong repression of biofilm formation under high-salinity conditions. The accumulation of compatible solutes such as glycine betaine aids the cells to cope with water stress by maintaining physiologically adequate levels of turgor and also affects multiple cellular processes through interactions with cellular components. Therefore, we additionally analysed the global effects of glycine betaine on the transcriptome and proteome of B. subtilis and revealed that it influences gene expression not only under high-salinity, but also under standard growth conditions., (© 2020 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

Upon competence-inducing nutrient-limited conditions, only part of the Bacillus subtilis population becomes competent. Here, we separated the two subpopulations by fluorescence-assisted cell sorting (FACS). Using RNA-seq, we confirmed the previously described ComK regulon. We also found for the first time significantly downregulated genes in the competent subpopulation. The downregulated genes are not under direct control by ComK but have higher levels of corresponding antisense RNAs in the competent subpopulation. During competence, cell division and replication are halted. By investigating the proteome during competence, we found higher levels of the regulators of cell division, MinD and Noc. The exonucleases SbcC and SbcD were also primarily regulated at the post-transcriptional level. In the competent subpopulation, yhfW was newly identified as being highly upregulated. Its absence reduces the expression of comG, and has a modest, but statistically significant effect on the expression of comK. Although expression of yhfW is higher in the competent subpopulation, no ComK-binding site is present in its promoter region. Mutants of yhfW have a small but significant defect in transformation. Metabolomic analyses revealed significant reductions in tricarboxylic acid (TCA) cycle metabolites and several amino acids in a ΔyhfW mutant. RNA-seq analysis of ΔyhfW revealed higher expression of the NAD synthesis genes nadA, nadB and nadC., (© 2020 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

Under hyperosmotic conditions, bacteria accumulate compatible solutes through synthesis or import. Bacillus subtilis imports a large set of osmostress protectants via five osmotically controlled transport systems (OpuA to OpuE). Biosynthesis of the particularly effective osmoprotectant glycine betaine requires the exogenous supply of choline. While OpuB is rather specific for choline, OpuC imports a broad spectrum of compatible solutes, including choline and glycine betaine. One previously mapped antisense RNA of B. subtilis , S1290, exhibits strong and transient expression in response to a suddenly imposed salt stress. It covers the coding region of the opuB operon and is expressed from a strictly SigB-dependent promoter. By inactivation of this promoter and analysis of opuB and opuC transcript levels, we discovered a time-delayed osmotic induction of opuB that crucially depends on the S1290 antisense RNA and on the degree of the imposed osmotic stress. Time-delayed osmotic induction of opuB is apparently caused by transcriptional interference of RNA-polymerase complexes driving synthesis of the converging opuB and S1290 mRNAs. When our data are viewed in an ecophysiological framework, it appears that during the early adjustment phase of B. subtilis to acute osmotic stress, the cell prefers to initially rely on the transport activity of the promiscuous OpuC system and only subsequently fully induces opuB . Our data also reveal an integration of osmostress-specific adjustment systems with the SigB-controlled general stress response at a deeper level than previously appreciated., (Copyright © 2020 Rath, Reder, Hoffmann, Hammer, Seubert, Bremer, Völker and Mäder.)

Using the original approach, a series of metallated N-confused porphyrins and metallated porphyrins have been synthesized and characterized. For all the synthesized porphyrins, in vitro studies of cytotoxic activity against K562, U937, HL-60, Jurkat, A549 and HeLa cancer cell lines, the ability to induce apoptosis and effects on the cell cycle as well as the kinetics of proliferative activity of porphyrins and their respective metallated complexes in real time have been developed. The inhibitory activity of metallated porphyrins against human topoisomerase I and the possible mechanism of inhibition have been carried out by modelling using molecular docking., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

High-yield synthesis, spectroscopic and solid-state structural proof of the lactam-embedded smallest ever metal-free stable Hückel antiaromatic trans -doubly N-confused [16] porphyrins are reported. These new facets of trans -doubly N-confused porphyrins have been anticipated to exhibit the redox-associated variation of Hückel aromaticity as a mere consequence of the amido-like structures of the N-confused N-methyl pyrrole rings of the macrocycles. Strong aromaticity upon NaBH 4 reduction leading to a resonance dipolar structure of the [18]π-conjugated system as the reduced congener with concomitant Hückel topology are the important highlights. Excellent agreement between experimental spectroscopic measurements and the theoretically determined properties elucidate aromaticity switching upon chemical reduction. Recent years have witnessed an upsurge of demand for the experimental realization of stable antiaromatic systems because of their versatile applications in material science. The conformational rigidity and the enriched stability of these novel 16π antiaromatic doubly N-confused porphyrins might entitle these macrocycles toward such applications.