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Size-Dependent Optical Band Gaps in Metal–Organic Framework Nanoparticles
Unveiling the Plasmodium inositol (pyro)phosphate pathway: Highlighting inositol polyphosphate multikinase as a novel therapeutic target for malaria
Plasmodium falciparum malaria is fatal if left untreated. Treatment is hampered by drug-resistant variants of the malaria parasite, highlighting the need to explore unique pathways for the development of new drugs with different mechanisms of action. Kinases in the inositol phosphate signaling pathway (IPP), and its products play many important roles in energy metabolism and signal transduction, making them attractive drug targets. In this exploratory study we investigated the potential of P. falciparum IPP as a novel and attractive pathway for antimalarial drug discovery, employing a combined in silico and molecular approach. The sequences and structures of the putative P. falciparum inositol phosphate kinases were characterized in silico . Experimental validation across laboratory strains and a clinical isolate confirmed the p.Pro375Gln substitution in IPMK1, providing the first evidence of this variant in field isolates. We provide molecular evidence of the existence of IPP genes in P. falciparum and suggest that targeting this pathway could be detrimental to the parasite. We identify P. falciparum inositol polyphosphate multikinase (IPMK) as a promising drug target due to its unique sequence and structural characteristics. These results serve as a guide for future experimental validation.
Catalytic Enantioselective Synthesis of Planar-Chiral Cyclophanes via a Chiral Octahedral Cobalt(III)-Templated C–H Macrocyclization
Comparative effects of combined aerobic and resistance training versus high-intensity interval training on insulin resistance, glycaemic control, body composition and quality of life in type 2 diabetes: A 12-week randomised controlled trial
Background Exercise training is a cornerstone in managing type 2 diabetes mellitus (T2DM), yet direct comparisons between combined aerobic–resistance training (A + R) and high-intensity interval training (HIIT) across clinical and patient-reported outcomes remain limited. Objective To compare the effects of A + R and HIIT on insulin resistance, glycaemic control, body composition, physical function, and quality of life in adults with T2DM, relative to standard care. Design and participants A single-centre, randomised controlled trial involving 90 participants with T2DM (aged 30–65 years), allocated to A + R, HIIT, or control groups. Interventions A + R consisted of moderate-intensity aerobic and resistance exercises, while HIIT comprised structured interval sessions. Both programs were delivered 3–5 times weekly for 12 weeks. The control group received usual care without structured exercise. Measurements Primary outcomes included fasting insulin (FI), Glycosylated Hemoglobin (HbA1c), and insulin resistance (HOMA-IR). Secondary outcomes included fasting glucose (FG), 6-minute walk distance (6MWD), subcutaneous and visceral fat, muscle mass, and WHOQOL-BREF domains. Results Compared with control, the HIIT group showed a greater reduction in fasting glucose (Mean Difference [MD] −29.1 mg/dL; 95% CI −41.2 to −17.0) and the A+R group also improved (MD −20.6 mg/dL; 95% CI −31.0 to −10.2). HbA1c was lower versus control in both HIIT (MD −3.35%; 95% CI −4.11 to −2.58) and A+R (MD −3.33%; 95% CI −4.03 to −2.62). Fasting insulin decreased relative to control in HIIT (MD −7.16 mIU/L; 95% CI −10.04 to −4.28) and A+R (MD −8.87 mIU/L; 95% CI −11.77 to −5.97). HOMA-IR improved versus control in A+R (MD −2.33; 95% CI −3.63 to −1.03) with a non-significant trend in HIIT (MD −1.17; 95% CI −2.47 to 0.13). Functional capacity (6-minute walk distance) increased versus control in HIIT (MD +178.9 m; 95% CI 130.5 to 227.4) and A+R (MD +233.6 m; 95% CI 191.8 to 275.5). Body composition favored both interventions: fat-free mass increased (HIIT MD +7.54 kg; 95% CI 4.71 to 10.36; A+R MD +5.96 kg; 95% CI 3.06 to 8.86) while subcutaneous fat (HIIT MD −7.16%; 95% CI −9.33 to −4.99; A+R MD −8.37%; 95% CI −10.65 to −6.09) and visceral fat (HIIT MD −4.70%; 95% CI −5.93 to −3.47; A+R MD −4.58%; 95% CI −5.86 to −3.31) were reduced. Quality of life improved across domains versus control in both groups (e.g., physical domain: HIIT MD +10.29; 95% CI 4.06 to 16.51; A+R MD +13.77; 95% CI 6.62 to 20.91). All results were derived from covariate-adjusted mixed models with multiple comparison corrections (Benjamini–Hochberg FDR, q = 0.05; Bonferroni-adjusted α = 0.002). Limitations Findings are limited to adherent participants, and generalizability is restricted to those without advanced complications. The 12-week duration precludes assessment of long-term sustainability. Conclusion Both HIIT and A+R significantly improved metabolic, functional, and psychosocial outcomes compared with control. HIIT yielded greater benefits for fasting glucose and muscle mass, while A+R conferred broader improvements in HbA1c, fat reduction, and quality of life. These findings support tailoring exercise prescriptions to therapeutic goals and highlight the complementary roles of HIIT and A+R in routine diabetes care. Clinical trial registration The trial is registered with the Clinical Trial Registry of India (reference no: CTRI/2022/04/041762).