Understanding the mechanisms underlying M. tuberculosis adaptive strategies to achieve drug tolerance is crucial for the identification of new targets and the development of new drugs. Here, we show that acetate medium triggers a drug-tolerant state in M. tuberculosis when challenged with antituberculosis (anti-TB) drugs.

Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide. Despite various campaigns towards the eradication of yaws and elimination of syphilis, these two diseases are still present in Ghana. The aetiological agents of both diseases, two Treponema pallidum subspecies, are genetically similar. This study aimed to assess the prevalence of these treponematoses and the occurrence of pathogens causing similar skin lesions in the Ashanti region of Ghana. A point-of-care test was used to determine the seroprevalence of the treponematoses. Both yaws and syphilis were identified in the Ashanti region of Ghana. Multiplex PCR was used to identify treponemes and other pathogens that cause similar skin lesions. The results indicated that the seroprevalences of T. pallidum in individuals with yaws-like and syphilis-like lesions were 17.2% and 10.8%, respectively. Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively. Among syphilis-like lesions, 28.3% were positive for herpes simplex virus -2 (HSV-2) by PCR. To our knowledge, this is the first time HSV-I and HSV-2 have been reported from yaws-like and syphilis-like lesions, respectively, in Ghana. The presence of other organisms apart from T. pallidum in yaws-like and syphilis-like lesions could impede the total healing of these lesions and the full recovery of patients. This may complicate efforts to achieve yaws eradication by 2030 and the elimination of syphilis and warrants updated empirical treatment guidelines for skin ulcer diseases.

Antimalarial chloroquine (CQ) prevents haematin detoxication when CQ-base concentrates in the acidic digestive vacuole through protonation of its p-aminopyridine (pAP) basic aromatic nitrogen and sidechain diethyl-N. CQ export through the variant vacuolar membrane export channel, PFCRT, causes CQ-resistance in Plasmodium falciparum but 3-methyl CQ (sontochin SC), des-ethyl amodiaquine (DAQ) and bis 4-aminoquinoline piperaquine (PQ) are still active. This is determined by changes in drug accumulation ratios in parasite lipid (LAR) and in vacuolar water (VAR). Higher LAR may facilitate drug binding to and blocking PFCRT and also aid haematin in lipid to bind drug. LAR for CQ is only 8.3; VAR is 143,482. More hydrophobic SC has LAR 143; VAR remains 68,523. Similarly DAQ with a phenol substituent has LAR of 40.8, with VAR 89,366. In PQ, basicity of each pAP is reduced by distal piperazine N, allowing very high LAR of 973,492, retaining VAR of 104,378. In another bis quinoline, dichlorquinazine (DCQ), also active but clinically unsatisfactory, each pAP retains basicity, being insulated by a 2-carbon chain from a proximal nitrogen of the single linking piperazine. While LAR of 15,488 is still high, the lowest estimate of VAR approaches 4.9 million. DCQ may be expected to be very highly lysosomotropic and therefore potentially hepatotoxic. In 11 pAP antimalarials a quadratic relationship between logLAR and logResistance Index (RI) was confirmed, while log (LAR/VAR) vs logRI for 12 was linear. Both might be used to predict the utility of structural modifications.

Despite their importance in cancer treatment, anticancer compounds face significant challenges due to drug resistance and low specificity, creating an urgent need for the discovery of more effective alternative. Herein, we report the synthesis of eleven 3-aminoimidazole[1,2-α]pyridine compounds (9–19) employing the one-pot Groebke-Blackburn-Bienayme three-component reaction (GBB-3CR). The cytotoxicity of the synthesised compounds was evaluated against three cancer cell lines (MCF-7, HT-29, B16F10) and a normal cell (MEF). Considering effectiveness and safety, the results demonstrated that among the eleven synthesised compounds, only compounds 12 and 14 exhibited high inhibitory activity against cancer cell lines. Compound 12 with a nitro group at the C-2 position and a p-chlorophenyl group at C-3 position, showed the highest inhibitory activity against HT-29, with an IC₅₀ of 4.15 ± 2.93 µM. Additionally, compound 14, with a tolyl moiety at the C-2 position and a p-chlorophenyl amine at C-3 position, can also be considered a promising bioactive product against B16F10, with an IC₅₀ of 21.75 ± 0.81 µM. Further research on these compounds may yield more potent candidates for the development of new anticancer agents. Graphic

Pollution from industrial activities, including heavy metal contamination, poses severe environmental challenges, especially in industrialized regions. This study evaluates reclamation efforts at the Kokzhon phosphorite deposit in Kazakhstan’s semi-desert zone, where over 67 million tons of industrial waste have accumulated across 3.3 thousand hectares. Reclamation efforts encompassed the treatment of 6,400 hectares using carbamide amendments and the planting of resilient phytomeliorants, including Russian Olive, Black Saxaul, Androsov Elm, and Salt Cedar. While tree survival rates were low (11%), herbaceous vegetation achieved remarkable success, with legumes and cereals attaining 95% growth rates. Herbaceous productivity increased from 2,200 kg/ha in 2013 to 3,300 kg/ha in 2018, alongside vegetation cover expanding from 60% to 80%. Soil fertility also improved significantly, with humus content rising from 0.18% in 2012 to 1.14% in 2023. Despite these improvements, the long-term impacts of industrial phosphorite mining continue to challenge ecosystem recovery. Over a 12-year period, reductions in humus content (47.6%) and herbaceous productivity (28.4%) have been observed, highlighting the need for enhanced soil management strategies to sustain reclamation outcomes. The results emphasize the potential of biological reclamation to restore degraded semi-desert ecosystems while underscoring the necessity of scalable, cost-effective solutions and long-term monitoring to mitigate ongoing environmental damage.