Chemical optimization and derivatization of micrococcin p2 to target multiple bacterial infections: new antibiotics from thiopeptides.

Antimicrobial resistance poses a significant threat to humanity, and the development of new antibiotics is urgently needed. Our research has focused on thiopeptide antibiotics such as micrococcin P2 (MP2) and derivatives thereof as new anti-infective agents. Thiopeptides are sulfur-rich, structurally complex substances that exhibit potent activity against Gram-positive pathogens and Mycobacteria species, including clinically resistant strains. The clinical development of thiopeptides has been hampered by the lack of efficient synthetic platforms to conduct detailed structure-activity relationship studies of these natural products. The present contribution touches upon efficient synthetic routes to MP2 that laid the groundwork for clinical translation. The medicinal chemistry campaign on MP2 has been guided by computational molecular dynamic simulations and parallel investigations to improve drug-like properties, such as enhancing the aqueous solubility and optimizing antibacterial activity. Such endeavors have enabled identification of promising lead compounds, AJ-037 and AJ-206, against Mycobacterium avium complex (MAC). Extensive in vitro studies revealed that these compounds exert potent activity against MAC species, a subspecies of non-tuberculous mycobacteria (NTM) that proliferate inside macrophages. Two additional pre-clinical candidates have been identified: AJ-024, for the treatment of Clostridioides difficile infections, and AJ-147, for methicillin-resistant Staphylococcus aureus impetigo. Both compounds compare quite favorably with current first-line treatments. In particular, the ability of AJ-147 to downregulate pro-inflammatory cytokines adds a valuable dimension to its clinical use. In light of above, these new thiopeptide derivatives are well-poised for further clinical development.

The impact of movement path of sesame seeds (Sesamum indicum L.) during treatment with intense pulsed light (IPL) using a continuous pilot-scale device on the reduction of indigenous microorganisms.

The objective of this study was to enhance the microbial inactivation efficacy of sesame seeds through the utilization of a pilot-scale IPL device, while also identifying the process variables that influence the microbial inactivation effect. Three different types of IPL processes were employed, each with a distinct arrangement, to treat sesame seeds. The total fluences applied ranged from 1.33 to 53.94 J/cm2. Total aerobic bacteria and fungi exhibited a maximum reduction of 2.27 and 2.77 log, respectively. The curved pathway of the sample flow effectively extended the duration of exposure to the IPL emitted by the lamps. The arrangement of the IPL process using two lamps in parallel but at different locations proved the most efficient for microbial inactivation. The application of IPL was found to be effective in reducing the presence of indigenous microbes in sesame seeds while having no significant impact on the physicochemical properties of the seeds.

ARHGEF5 binds Drebrin and affects α-tubulin acetylation to direct neuronal morphogenesis and migration during mouse brain development.

Rho guanine nucleotide exchange factors (Rho GEFs) activate Rho GTPases, which act as molecular switches regulating various essential cellular functions. This study investigated the role of ARHGEF5, a Rho GEF known for its involvement in cell migration and invasion processes, in the context of brain development. We found that ARHGEF5 is essential for dendrite development during the early stages of neuronal growth. We also discovered that ARHGEF5 binds to Drebrin E, which is vital for coordinating actin and microtubule dynamics, and facilitates the interaction between Drebrin E and Cyclin-dependent kinase 5, which phosphorylates Drebrin E. Notably, ARHGEF5 deficiency resulted in a decrease in acetylated α-tubulin levels, and the expression of an α-tubulin acetylation mimetic mutant (K40Q) rescued the defects in dendrite development and neuronal migration, suggesting ARHGEF5's role in modulating microtubule stability. Additionally, ARHGEF5 was shown to influence Golgi positioning in the leading processes of migrating cortical neurons during brain development. Our study suggests that ARHGEF5 plays a crucial role in integrating cytoskeletal dynamics with neuronal morphogenesis and migration processes during brain development.

Complete mitochondrial genome of the European common barnacle Perforatus perforatus Bruguière, 1789 (balanomorpha: balanidae).

This study is the first to sequence the complete mitochondrial genome (mitogenome) of Perforatus perforatus Bruguière, 1789 (Balanomorpha: Balanidae). The 15,536-bp long P. perforatus mitogenome contained a typical set of animal mitochondrial genes, along with one control region. The P. perforatus mitogenome had an inverted gene block (trnP-ND4L-ND4-trnH-ND5-trnF) between trnS(gct) and trnT. This inverted gene block had been detected six species in three subfamilies of the Balanidae family (Balaninae, Acastinae and Megabalaninae), but our results show that it is also present in Concavinae, in which P. perforatus is included. The phylogenetic tree based on the concatenated sequences of the 13 protein-coding genes and two rRNA genes showed that P. perforatus is closely associated with Acasta sulcate and Balanus trigonus within Balanidae.

Optimal approach for diagnosing peripheral lung nodules by combining electromagnetic navigation bronchoscopy and radial probe endobronchial ultrasound.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) and radial probe endobronchial ultrasound (RP-EBUS) are essential bronchoscopic procedures for diagnosing peripheral lung lesions. Despite their individual advantages, the optimal circumstances for their combination remain uncertain. METHODS: This single-center retrospective study enrolled 473 patients with 529 pulmonary nodules who underwent ENB and/or RP-EBUS biopsies between December 2021 and December 2022. Diagnostic yield was calculated using strict, intermediate, and liberal definitions. In the strict definition, only malignant and specific benign lesions were deemed diagnostic at the time of the index procedure. The intermediate and liberal definitions included additional results from the follow-up period. RESULTS: The diagnostic yield of the strict definition was not statistically different among the three groups (ENB/Combination/RP-EBUS 63.8%/64.2%/62.6%, p = 0.944). However, the diagnostic yield was superior in the ENB + RP-EBUS group for nodules with a bronchus type II or III and a solid part <20 mm (odds ratio 1.96, 95% confidence interval 1.09-3.53, p = 0.02). In terms of complications, bleeding was significantly higher in the ENB + RP-EBUS group (ENB/Combination/RP-EBUS 3.7% /6.2/0.6%, p = 0.002), but no major adverse event was observed. CONCLUSION: The combination of ENB and RP-EBUS enhanced the diagnostic yield for nodules with bronchus type II or III and solid part <20 mm, despite a slightly elevated risk of bleeding. Careful patient selection based on nodule characteristics is important to benefit from this combined approach.

Recent Update on PET/CT Radiotracers for Imaging Cerebral Glioma.

Positron emission tomography/computed tomography (PET/CT) has dramatically altered the landscape of noninvasive glioma evaluation, offering complementary insights to those gained through magnetic resonance imaging (MRI). PET/CT scans enable a multifaceted analysis of glioma biology, supporting clinical applications from grading and differential diagnosis to mapping the full extent of tumors and planning subsequent treatments and evaluations. With a broad array of specialized radiotracers, researchers and clinicians can now probe various biological characteristics of gliomas, such as glucose utilization, cellular proliferation, oxygen deficiency, amino acid trafficking, and reactive astrogliosis. This review aims to provide a recent update on the application of versatile PET/CT radiotracers in glioma research and clinical practice.

Transcriptome sequencing of the endangered land snail Karaftohelix adamsi from the Island Ulleung: De novo assembly, annotation, valuation of fitness genes and SSR markers.

BACKGROUND: The Bradybaenidae snail Karaftohelix adamsi is endemic to Korea, with the species tracked from Island Ulleung in North Gyeongsang Province of South Korea. K. adamsi has been classified under the Endangered Wildlife Class II species of Korea and poses a severe risk of extinction following habitat disturbances. With no available information at the DNA (genome) or mRNA (transcriptome) level for the species, conservation by utilizing informed molecular resources seems difficult. OBJECTIVE: In this study, we used the Illumina short-read sequencing and Trinity de novo assembly to draft the reference transcriptome of K. adamsi. RESULTS: After assembly, 13,753 unigenes were obtained of which 10,511 were annotated to public databases (a maximum of 10,165 unigenes found homologs in PANM DB). A total of 6,351, 3,535, 358, and 3,407 unigenes were ascribed to the functional categories under KOG, GO, KEGG, and IPS, respectively. The transcripts such as the HSP 70, aquaporin, TLR, and MAPK, among others, were screened as putative functional resources for adaptation. DNA transposons were found to be thickly populated in comparison to retrotransposons in the assembled unigenes. Further, 2,164 SSRs were screened with the promiscuous presence of dinucleotide repeats such as AC/GT and AG/CT. CONCLUSION: The transcriptome-guided discovery of molecular resources in K. adamsi will not only serve as a basis for functional genomics studies but also provide sustainable tools to be utilized for the protection of the species in the wild. Moreover, the development of polymorphic SSRs is valuable for the identification of species from newer habitats and cross-species genotyping.

[18F]FDG PET/CT is useful in discriminating invasive adenocarcinomas among pure ground-glass nodules: comparison with CT findings-a bicenter retrospective study.

PURPOSE: Predicting the malignancy of pure ground-glass nodules (GGNs) using CT is challenging. The optimal role of [18F]FDG PET/CT in this context has not been clarified. We compared the performance of [18F]FDG PET/CT in evaluating GGNs for predicting invasive adenocarcinomas (IACs) with CT. METHODS: From June 2012 to December 2020, we retrospectively enrolled patients with pure GGNs on CT who underwent [18F]FDG PET/CT within 90 days. Overall, 38 patients with 40 ≥ 1-cm GGNs were pathologically confirmed. CT images were analyzed for size, attenuation, uniformity, shape, margin, tumor-lung interface, and internal/surrounding characteristics. Visual [18F]FDG positivity, maximum standardized uptake value (SUVmax), and tissue fraction-corrected SUVmax (SUVmaxTF) were evaluated on PET/CT. RESULTS: The histopathology of the 40 GGNs were: 25 IACs (62.5%), 9 minimally invasive adenocarcinomas (MIA, 22.5%), and 6 adenocarcinomas in situ (AIS, 15.0%). No significant differences were found in CT findings according to histopathology, whereas visual [18F]FDG positivity, SUVmax, and SUVmaxTF were significantly different (P=0.001, 0.033, and 0.018, respectively). The size, visual [18F]FDG positivity, SUVmax, and SUVmaxTF showed significant diagnostic performance to predict IACs (area under the curve=0.693, 0.773, 0.717, and 0.723, respectively; P=0.029, 0.001, 0.018, and 0.013, respectively). In the multivariate logistic regression analysis, visual [18F]FDG positivity discriminated IACs among GGNs among various CT and PET findings (P=0.008). CONCLUSIONS: [18F]FDG PET/CT demonstrated superior diagnostic performance compared to CT in differentiating IAC from AIS/MIA among pure GGNs, thus it has the potential to guide the proper management of patients with pure GGNs.

A new model using deep learning to predict recurrence after surgical resection of lung adenocarcinoma.

This study aimed to develop a deep learning (DL) model for predicting the recurrence risk of lung adenocarcinoma (LUAD) based on its histopathological features. Clinicopathological data and whole slide images from 164 LUAD cases were collected and used to train DL models with an ImageNet pre-trained efficientnet-b2 architecture, densenet201, and resnet152. The models were trained to classify each image patch into high-risk or low-risk groups, and the case-level result was determined by multiple instance learning with final FC layer's features from a model from all patches. Analysis of the clinicopathological and genetic characteristics of the model-based risk group was performed. For predicting recurrence, the model had an area under the curve score of 0.763 with 0.750, 0.633 and 0.680 of sensitivity, specificity, and accuracy in the test set, respectively. High-risk cases for recurrence predicted by the model (HR group) were significantly associated with shorter recurrence-free survival and a higher stage (both, p < 0.001). The HR group was associated with specific histopathological features such as poorly differentiated components, complex glandular pattern components, tumor spread through air spaces, and a higher grade. In the HR group, pleural invasion, necrosis, and lymphatic invasion were more frequent, and the size of the invasion was larger (all, p < 0.001). Several genetic mutations, including TP53 (p = 0.007) mutations, were more frequently found in the HR group. The results of stages I-II were similar to those of the general cohort. DL-based model can predict the recurrence risk of LUAD and identify the presence of the TP53 gene mutation by analyzing histopathologic features.

Lowering Barriers to Health Risk Assessments in Promoting Personalized Health Management.

This study investigates the feasibility of accurately predicting adverse health events without relying on costly data acquisition methods, such as laboratory tests, in the era of shifting healthcare paradigms towards community-based health promotion and personalized preventive healthcare through individual health risk assessments (HRAs). We assessed the incremental predictive value of four categories of predictor variables-demographic, lifestyle and family history, personal health device, and laboratory data-organized by data acquisition costs in the prediction of the risks of mortality and five chronic diseases. Machine learning methodologies were employed to develop risk prediction models, assess their predictive performance, and determine feature importance. Using data from the National Sample Cohort of the Korean National Health Insurance Service (NHIS), which includes eligibility, medical check-up, healthcare utilization, and mortality data from 2002 to 2019, our study involved 425,148 NHIS members who underwent medical check-ups between 2009 and 2012. Models using demographic, lifestyle, family history, and personal health device data, with or without laboratory data, showed comparable performance. A feature importance analysis in models excluding laboratory data highlighted modifiable lifestyle factors, which are a superior set of variables for developing health guidelines. Our findings support the practicality of precise HRAs using demographic, lifestyle, family history, and personal health device data. This approach addresses HRA barriers, particularly for healthy individuals, by eliminating the need for costly and inconvenient laboratory data collection, advancing accessible preventive health management strategies.

Ultrahigh Photoresponsivity of W/Graphene/ß-Ga2O3 Schottky Barrier Deep Ultraviolet Photodiodes.

The integration of graphene with semiconductor materials has been studied for developing advanced electronic and optoelectronic devices. Here, we propose ultrahigh photoresponsivity of ß-Ga2O3 photodiodes with a graphene monolayer inserted in a W Schottky contact. After inserting the graphene monolayer, we found a reduction in the leakage current and ideality factor. The Schottky barrier height was also shown to be about 0.53 eV, which is close to an ideal value. This was attributed to a decrease in the interfacial state density and the strong suppression of metal Fermi-level pinning. Based on a W/graphene/ß-Ga2O3 structure, the responsivity and external quantum efficiency reached 14.49 A/W and 7044%, respectively. These values were over 100 times greater than those of the W contact alone. The rise and delay times of the W/graphene/ß-Ga2O3 Schottky barrier photodiodes significantly decreased to 139 and 200 ms, respectively, compared to those obtained without a graphene interlayer (2000 and 3000 ms). In addition, the W/graphene/ß-Ga2O3 Schottky barrier photodiode was highly stable, even at 150 °C.

Prognostic value of CT-based radiomics in grade 1-2 pancreatic neuroendocrine tumors.

BACKGROUND: Surgically resected grade 1-2 (G1-2) pancreatic neuroendocrine tumors (PanNETs) exhibit diverse clinical outcomes, highlighting the need for reliable prognostic biomarkers. Our study aimed to develop and validate CT-based radiomics model for predicting postsurgical outcome in patients with G1-2 PanNETs, and to compare its performance with the current clinical staging system. METHODS: This multicenter retrospective study included patients who underwent dynamic CT and subsequent curative resection for G1-2 PanNETs. A radiomics-based model (R-score) for predicting recurrence-free survival (RFS) was developed from a development set (441 patients from one institution) using least absolute shrinkage and selection operator-Cox regression analysis. A clinical model (C-model) consisting of age and tumor stage according to the 8th American Joint Committee on Cancer staging system was built, and an integrative model combining the C-model and the R-score (CR-model) was developed using multivariable Cox regression analysis. Using an external test set (159 patients from another institution), the models' performance for predicting RFS and overall survival (OS) was evaluated using Harrell's C-index. The incremental value of adding the R-score to the C-model was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The median follow-up periods were 68.3 and 59.7 months in the development and test sets, respectively. In the development set, 58 patients (13.2%) experienced recurrence and 35 (7.9%) died. In the test set, tumors recurred in 14 patients (8.8%) and 12 (7.5%) died. In the test set, the R-score had a C-index of 0.716 for RFS and 0.674 for OS. Compared with the C-model, the CR-model showed higher C-index (RFS, 0.734 vs. 0.662, p = 0.012; OS, 0.781 vs. 0.675, p = 0.043). CR-model also showed improved classification (NRI, 0.330, p < 0.001) and discrimination (IDI, 0.071, p < 0.001) for prediction of 3-year RFS. CONCLUSIONS: Our CR-model outperformed the current clinical staging system in prediction of the prognosis for G1-2 PanNETs and added incremental value for predicting postoperative recurrence. The CR-model enables precise identification of high-risk patients, guiding personalized treatment planning to improve outcomes in surgically resected grade 1-2 PanNETs.

The association between migraine and Parkinson's disease: a nationwide cohort study.

OBJECTIVES: Clinical studies have suggested an association between migraine and the occurrence of Parkinson's disease (PD). However, it is unknown whether migraine affects PD risk. We aimed to investigate the incidence of PD in patients with migraine and to determine the risk factors affecting the association between migraine and PD incidence. METHODS: Using the Korean National Health Insurance System database (2002-2019), we enrolled all Koreans aged ≥40 years who participated in the national health screening program in 2009. International Classification of Diseases (10th revision) diagnostic codes and Rare Incurable Diseases System diagnostic codes were used to define patients with migraine (within 12 months of enrollment) and newly diagnosed PD. RESULTS: We included 214,193 patients with migraine and 5,879,711 individuals without migraine. During 9.1 years of follow-up (55,435,626 person-years), 1,973 (0.92%) and 30,664 (0.52%) individuals with and without migraine, respectively, were newly diagnosed with PD. Following covariate adjustment, patients with migraine showed a 1.35-fold higher PD risk than individuals without migraine. The incidence of PD was not significantly different between patients with migraine with aura and those without aura. In males with migraine, underlying dyslipidemia increased the risk of PD (p=0.012). In contrast, among females with migraine, younger age (<65 years) increased the risk of PD (p=0.038). CONCLUSIONS: Patients with migraine were more likely to develop PD than individuals without migraine. Preventive management of underlying comorbidities and chronic migraine may affect the incidence of PD in these patients. Future prospective randomized clinical trials are warranted to clarify this association.

Effect of environmental water activity on microbial inactivation by intense pulsed light (IPL).

In this study, the effect of environmental aw on microbial inactivation by intense pulsed light (IPL) was investigated. Three different microorganisms (Gram-positive bacteria, Gram-negative bacteria, and yeast) were used as test organisms. The effect of environmental aw was assessed by irradiating each microbial suspension in sodium chloride solutions with different environmental aw levels (0.99-0.80). As the aw decreased, the aggregation of intracellular material of cell interior was changed and the cell number was increased. However, there was no significant difference in microbial reduction according to the aw after the 0.23-3.05 J/cm2 of IPL treatment. It was confirmed that yeast had the highest resistance to IPL because of the differences in cell structure and cell wall components between yeast and bacteria. Additional research is needed to clearly understand the inactivation mechanism according to the type of microorganism by controlling aw using various solutes.

IFITM3-mediated activation of TRAF6/MAPK/AP-1 pathways induces acquired TKI resistance in clear cell renal cell carcinoma.

PURPOSE: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response. MATERIALS AND METHODS: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins. RESULTS: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways. CONCLUSIONS: These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.

Tumoural Pellino-1 expression and Pellino-1-expressive cytotoxic T-cells are associated with poor prognosis in diffuse large B-cell lymphoma.

Pellino-1 plays a role in regulating inflammation and immune responses, and its effects on tumours are complex, with different outcomes reported in various studies. Additionally, the role of Pellino-1 in diffuse large B-cell lymphoma (DLBCL) has not been thoroughly investigated. We aimed to examine the expression of Pellino-1 in tumour cells and tumour-infiltrating lymphocytes (TILs) separately and identify the clinicopathological significance of Pellino-1 expression in DLBCL. We evaluated Pellino-1 expression in 104 patients with DLBCL. The density of specific cell types was quantitatively analysed using digital image analysis after a multiplex immunofluorescence staining with Pellino-1, CD20, CD8, FOXP3, and PD-1. Pellino-1 expression was mostly observed in CD20+ tumour cells and CD8+ TILs. The high CD8+/Pellino-1+ group was significantly associated with the non-GCB subtype and higher numbers of Foxp3+ T-cells. Patients with high CD20+/Pellino-1+ and high CD8+/Pellino-1+ cell densities had significantly shorter event-free survival (EFS) rates. The multivariate Cox-regression analysis showed that CD20+/Pellino-1+ cell density and CD8+/Pellino-1+ cell density were independent poor prognostic factors for EFS. Furthermore, patients with low densities of both CD20+/Pellino-1+ and CD8+/Pellino-1+ cells demonstrated a prognosis superior to that of patients with high Pellino-1+ cell densities, either alone or in combination. Additionally, the multivariate analysis demonstrated that the combination of CD20+/Pellino-1+ and CD8+/Pellino-1+ cell densities was an independent prognostic factor for EFS and overall survival. Pellino-1 expression was observed in both tumour cells and TILs, particularly in cytotoxic T-cells, and was correlated with poor outcomes in DLBCL. Thus, Pellino-1 might have an oncogenic effect on DLBCL and might be a potential target for improving cytotoxic T-cell activity.

Boosting the Output Performance of the MoS2 Monolayer-Based Piezoelectric Nanogenerator by Artificial Dual Strain Concentration.

Piezoelectric nanogenerators (PENGs) with molybdenum disulfide (MoS2) monolayers have been intensively studied owing to their superior mechanical durability and stability. However, the limited output performance resulting from a small active area and low strain levels continues to pose a significant challenge that should be overcome. Herein, we report a novel strategy for the epoch-making output performance of a PENG with a MoS2 monolayer by adopting the additive strain concentration concept. The simulation study indicates that strain in the MoS2 monolayer can be initially augmented by the wavy structure resulting from the prestretched poly(dimethylsiloxane) (PDMS) and is further increased through flexural deformation (i.e., bending). Based on these studies, we have developed concentrated strain-applied PENGs with MoS2 monolayers. The wavy structures effectively applied strain to the MoS2 monolayer and generated a piezoelectric output voltage and current of around 580 mV and 47.5 nA, respectively. Our innovative approach to enhancing the performance of PENGs with MoS2 monolayers through the artificial dual strain concept has led to groundbreaking results, achieving the highest recorded output voltage and current for PENGs based on two-dimensional (2D) materials, which provides unique opportunities for the 2D-based energy harvesting field and structural insight into how to improve the net strain on 2D materials.

Starch-Based Hydrogels as a Drug Delivery System in Biomedical Applications.

Starch-based hydrogels have gained significant attention in biomedical applications as a type of drug delivery system due to their biocompatibility, biodegradability, and ability to absorb and release drugs. Starch-based hydrogels can serve as effective carriers for pharmaceutical compounds such as drugs and proteins to develop drug-loaded hydrogel systems, providing controlled release over an extended period. The porous structure of a hydrogel allows for the diffusion of drugs, ensuring sustained and localized delivery to the target site. Moreover, starch-based hydrogels have been used as a powerful option in various biomedical fields, including cancer and infectious disease treatment. In addition, starch-based hydrogels have shown promise in tissue engineering applications since hydrogels can be used as scaffolds or matrices to support cell growth and tissue regeneration. Depending on techniques such as chemical crosslinking or physical gelation, it can create a three-dimensional network structure that tunes its mechanical properties and mimics the extracellular matrix. Starch-based hydrogels can also provide a supportive environment for cell attachment, proliferation, and differentiation to promote specific cellular responses and tissue regeneration processes with the loading of growth factors, cytokines, or other bioactive molecules. In this review, starch-based hydrogels as a versatile platform for various biomedical applications are discussed.

Therapies from Thiopeptides.

The first part of this contribution describes solutions that were developed to achieve progressively more efficient syntheses of the thiopeptide natural products, micrococcins P1 and P2 (MP1-MP2), with an eye toward exploring their potential as a source of new antibiotics. Such efforts enabled investigations on the medicinal chemistry of those antibiotics, and inspired the development of the kinase inhibitor, Masitinib®, two candidate oncology drugs, and new antibacterial agents. The studies that produced such therapeutic resources are detailed in the second part. True to the theme of this issue, "Organic Synthesis and Medicinal Chemistry: Two Inseparable Partners", an important message is that the above advances would have never materialized without the support of curiosity-driven, academic synthetic organic chemistry: a beleaguered science that nonetheless has been-and continues to be-instrumental to progress in the biomedical field.