Insect chitosan/pullulan/gallium photo-crosslinking hydrogels with multiple bioactivities promote MRSA-infected wound healing.

Methicillin-resistant Staphylococcus aureus (MRSA) and other drug-resistant bacteria have become more common in recent years, which has made it extremely difficult to treat and heal many different kinds of wounds and caused enormous financial losses. Because of its unique "Trojan horse" function, Ga3+ has been recognized as a new possible candidate for inhibiting and eradicating drug-resistant bacteria. Furthermore, natural polysaccharide materials with outstanding biological characteristics, such as insect chitosan (CS) and pullulan (PUL), have attracted significant interest. In this study, we used quaternized-catechol chitosan (QDCS-PA), methacrylate-dialdehyde pullulan (DPUL-GMA), and gallium ion (Ga) to create a multi-crosslinked photo-enhanced hydrogel (Q-D/Ga/UV) with antimicrobial, hemostatic, self-healing, and injectable properties for promoting MRSA-infected wound healing. In vitro, the Q-D/Ga/UV hydrogels demonstrated good mechanical properties, antioxidant capabilities, biocompatibility, hemostatic properties, and antibacterial activity. The addition of gallium ions enhanced the hydrogels' mechanical properties, hemostatic capabilities, antibacterial activity, and ability to induce wound healing. Q-D/Ga/UV hydrogel significantly promoted wound contraction, collagen deposition, and angiogenesis while also suppressing inflammation in a whole-skin wound model of MRSA-infected rats. In conclusion, Q-D/Ga/UV hydrogels demonstrate significant promise for healing wounds infected with drug-resistant bacteria.

Multiresponsive luminescent metal-organic framework for cooking oil adulteration detection and gallium(III) sensing.

A new 3D metal-organic framework {[Cd16(tr2btd)10(dcdps)16(H2O)3(EtOH)]∙15DMF}n (MOF 1, tr2btd = 4,7-di(1,2,4-triazol-1-yl)benzo-2,1,3-thiadiazole, H2dcdps = 4,4'-sulfonyldibenzoic acid) was obtained and its luminescent properties were studied. MOF 1 exhibited bright blue-green luminescence with a high quantum yield of 74 % and luminescence quenching response to a toxic natural polyphenol gossypol and luminescence enhancement response to some trivalent metal cations (Fe3+, Cr3+, Al3+ and Ga3+). The limit of gossypol detection was 0.20 µM and the determination was not interfered by the components of the cottonseed oil. The limit of detection of gallium(III) was 1.1 µM. It was demonstrated that MOF 1 may be used for distinguishing between the genuine sunflower oil and oil adulterated by crude cottonseed oil through qualitative luminescent and quantitative visual gossypol determination.

Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm.

Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.

Fabrication of peptide-encapsulated sodium alginate hydrogel for selective gallium adsorption.

Peptides are recognized as promising adsorbents in metal selective recovery. In this study, the designed gallium-binding peptide H6GaBP was immobilized by the polysaccharide polymer sodium alginate (SA) for gallium recovery. The synthesized H6GaBP@SA microspheres exhibited a maximum adsorption capacity of 127.4 mg/g and demonstrated high selectivity for gallium at lower pH values. The adsorption process aligned well with the pseudo-second-order equation and Langmuir model. To elucidate the adsorption mechanism, a comprehensive characterization including molecular docking, scanning electron microscope coupled with energy-dispersive X-ray spectroscopy (SEM-EDS), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and thermogravimetry analysis (TGA), were conducted. These analyses revealed that gallium ions were initially adsorbed through electrostatic interaction by H6GaBP@SA, followed by a cation exchange reaction between Ga(OH)2+ and Ca2+, as well as coordination between gallium and histidine residues on the peptide. Moreover, the H6GaBP@SA exhibited improved thermal stability compared to sole sodium alginate microspheres, and the coordination of gallium with peptides can also defer the decomposition rate of the adsorbents. Compared to other adsorbents, the peptide-encapsulated hydrogel microspheres exhibited superior gallium selectivity and improved adsorption capacity, offering an environmentally friendly option for gallium recovery.

Interaction of the III-As monolayer with SARS-CoV-2 biomarkers: implications for biosensor development.

The emergence of SARS-CoV-2 in 2019 led to the global COVID-19 pandemic, highlighting the urgency for developing cost-effective and non-invasive methods to detect diseases at an early stage. Human breath, rich in volatile organic compounds (VOCs), is promising for cost-effective and rapid disease detection, with specific VOCs like methanol, ethanal, butanone, acetone, and ethyl butyrate linked to COVID-19. Recent advances in biomarker detection and gas sensing with 2D materials, particularly III-As monolayers like BAs, GaAs, and AlAs, offer high sensitivity at low concentrations, providing a novel avenue for exploring their potential in detecting COVID-19 biomarkers. This article aims to examine the effects of adsorption on different properties of III-Arsenide (BAs, GaAs and AlAs) monolayers, particularly in connection with SARS-CoV-2 biomarkers. In order to examine the interaction between the monolayers and biomarkers, first-principles computations within the framework of density functional theory (DFT) are utilized. The present study involves an investigation of the modifications in the band structure, density of states (DOS), work function, electron density difference, and optical properties (reflectance and absorbance) of III-As monolayers, with the aim of assessing their viability for the detection of SARS-CoV-2 biomarkers along with interfering gases such as CO2 and H2O. It is observed that VOCs induce a notable change in the work function of GaAs which serves as an indicator of the presence of these biomarkers. However, the changes in work function are not as substantial as those for AlAs and BAs. Additionally, the chemiresistive sensitivity, optical sensitivity and recovery time of III-As are investigated. The findings suggest that the pristine GaAs monolayer displays a significant level of sensitivity and selectivity towards the SARS-CoV-2 biomarkers, rendering it a material with potential for utilization in sensing applications. Furthermore, it has been observed that the recovery time of the GaAs monolayer subsequent to its exposure to the VOC biomarkers lies within an acceptable threshold. Upon exposure to UV light, the recovery time is further reduced. The outcomes of our study indicate that GaAs monolayers exhibit considerable potential as chemiresistive, work function-based and optical sensors for the precise and discerning identification of VOCs linked to the SARS-CoV-2 virus compared to the other two III-As monolayers.

Synthesis, characterization and in vitro cytotoxicity of gallium(III)-dithiocarbamate complexes.

A library of homoleptic mononuclear Ga(III) complexes of the general formula [Ga(DTC)3], where DTC is an alicyclic or a linear dithiocarbamate chelator, is reported. The complexes were prepared in high yields starting from Ga(NO3)3·6H2O and fully characterized by elemental analysis and IR and NMR spectroscopy. Crystals of five of these complexes were obtained. The antitumor activity of the newly synthesized compounds against a panel of human cancer cell lines was evaluated. The chemical nature of the DTC does not have a marked impact on the structural features of the final compound. X-ray crystal structure analyses revealed that all these complexes have a trigonal prismatic geometry with three identical chelating DTCs coordinating the Ga(III) ion. It is noteworthy that in complex 22, [Ga(NHEt)3] (NHEt = N-ethyldithiocarbamate), the asymmetric unit is formed by two independent and structurally different molecules. Cellular studies showed that all the synthesized Ga-DTC complexes exhibit marked cytotoxic activity, even against human colon cancer cells that are less sensitive to cisplatin. Among the tested compounds, 6 ([Ga(CEPipDTC)3], CEPipDTC = (ethoxycarbonyl)-piperidinedithiocarbamate) and 21 ([Ga(Pr-13)3], PR13 = 4 and N-(2-ethoxy-2-oxoethyl)-N-methyldithiocarbamate) are very promising derivatives, but they have no selectivity towards cancer cells. Nevertheless, the obtained data provide a foundation for developing gallium-dithiocarbamate complexes as anticancer agents.

Magnetic and injectable Fe-doped liquid metals for controlled movement and photothermal/electromagnetic therapy.

As a multifunctional material, gallium-based liquid metal (LM) mixtures with metal particles dispersed in the LM environment display many excellent and intriguing properties. In this study, biomaterials were prepared by mixing Fe particles with LM for easily manageable photothermal or electromagnetic therapy and evaluated. Clinically, the fabricated 5%Fe/LM sample was injectable and radiopaque, which allowed its smooth delivery through a syringe to the target tissues, where it could help achieve clear imaging under CT. Meanwhile, because of the loading of Fe particles, the 5%Fe/LM possessed a magnetic property, implying a high manipulation capability. According to the experiments, the capsule containing 5%Fe/LM when placed in an isolated pig large intestine could move as desired to the designated position through an external magnet. Further, the biosafety and low toxicity of the 5%Fe/LM were confirmed by cytotoxicity tests in vitro, and the temperature changes at the interface between the 5%Fe/LM and intestinal tissue after near-infrared (NIR) laser irradiation were determined through theoretical modeling and numerical simulation data analysis. Due to the excellent photothermal and magnetothermal effects of LM, the temperature of the 5%Fe/LM injected into the rabbit abdominal cavity could significantly increase under NIR laser or alternating magnetic field (AMF) administration. As a novel functional biomaterial, the 5%Fe/LM exhibited promising potential for designated position movement and photothermal or magnetothermal therapy in the near future.

A New Concept in Antidiabetic Therapeutics: A Concerted Removal of Labile Iron and Intracellular Deposition of Zinc.

BACKGRUOUND: The inflammatory process is known to be an integral part of the pathophysiology of type 2 diabetes mellitus (T2DM). The "labile," redox-active iron, serving as a catalyst in Fenton reaction, producing the deleterious reactive oxygen species, triggering and maintaining inflammation, is hypothesized to play a causative role in this process. Concenter Biopharma continued the development of a new platform of iron chelators (Zygosids), first initiated at the Hebrew University of Jerusalem, Israel (HUJI), acting via the novel mechanism, based on a sequestration of the labile redox-active iron and its substitution by zinc or gallium. The mode of action of Zygosids is based on the higher affinity of the metal-binding moiety of the complex to Fe3+ in comparison to already bound ion, leading to rapid release of the ion of another metal and chelation of Fe3+. Concomitantly, zinc ion, released by the complex, is known for its antidiabetic and anti-inflammatory role. METHODS: The therapeutic effect of zinc-desferrioxamine (Zygosid-50) and gallium-desferrioxamine, was tested on fat sand rat (Psammomys obesus) model of diet-induced T2DM and on Leprdb transgenic diabetic mice. RESULTS: Zygosids demonstrated an ability to noticeably reduce blood glucose and insulin levels and improve the lipid profile. Moreover, an ability to mitigate insulin resistance by >90% was shown on the sand rat model. In addition, a potent anti-inflammatory effect, expressed as a diminishment of the proinflammatory cytokines in tissue levels, was demonstrated. CONCLUSION: Zygosids demonstrated robust therapeutic efficacy in treatment of T2DM. Importantly, no adverse effects were detected, in all the experiments, indicating high safety profile.

Boron deficiency decreased the root activity of Ga-exposed rice seedlings by reducing iron accumulation and increasing Ga in iron plaque.

Gallium (Ga) is an emerging chemical pollutant chiefly associated with high-tech industries. Boron (B) alleviates the negative effects of toxic elements on plant growth. Thereby, the effects of B fertilization on Ga toxicity in rice seedlings was studied to clarify the role of iron plaque in the distribution of Ga, Fe, and B in Ga-treated rice seedlings in the presence or absence of B. Gallium exposure significantly reduced the biomass of rice seedlings. Boron deficiency induced a significant change in the distribution of B in Ga-treated rice seedlings compared with "Ga+B" treatments. Accumulation of Ga in roots, dithionite-citrate-bicarbonate (DCB) extracts, and shoots showed a dose-dependent manner from both +B and -B rice seedlings. Boron nutrition levels affect the distribution of Fe in roots, DCB extracts, and shoots, in which DCB-extractable Fe was significantly decreased from "Ga-B" treatments compared with "Ga+B" treatments. Root activity was significantly decreased in both Ga-exposed rice seedlings; however, B-deficient seedlings showed a severe reduction than +B rice seedlings. These results reveal that Fe plaque might be a temporary sink for B accumulation when plants are grown with proper B, wherein the re-utilization of DCB-extractable B stored in Fe plaque is mandatory for plant growth under B deficiency. Correlation analysis revealed that B deficiency decreased the root activity of Ga-exposed rice seedlings by reducing DCB-extractable Fe and increasing DCB-extractable Ga in Fe plaque. This study enhances our understanding of how B nutritional levels affect Ga toxicity in rice plants.

An integrated wearable sticker based on extended-gate AlGaN/GaN high electron mobility transistors for real-time cortisol detection in human sweat.

Cortisol hormone imbalances can be detected through non-invasive sweat monitoring using field-effect transistor (FET) biosensors, which provide rapid and sensitive detection. However, challenges like skin compatibility and integration with sweat collection have hindered FET biosensors as wearable sensing platforms. In this study, we present an integrated wearable sticker for real-time cortisol detection based on an extended-gate AlGaN/GaN high electron mobility transistor (HEMT) combined with a soft bottom substrate and flexible channel for sweat collection. The developed devices exhibit excellent linearity (R2 = 0.990) and a high sensitivity of 1.245 µA dec-1 for cortisol sensing from 1 nM to 100 µM in high-ionic-strength solution, with successful cortisol detection demonstrated using authentic human sweat samples. Additionally, the chip's microminiature design effectively reduces bending impact during the wearable process of traditional soft binding sweat sensors. The extendedgate structure design of the HEMT chip enhances both width-to-length ratio and active sensing area, resulting in an exceptionally low detection limit of 100 fM. Futhermore, due to GaN material's inherent stability, this device exhibits long-term stability with sustained performance within a certain attenuation range even after 60 days. These stickers possess small, lightweight, and portable features that enable real-time cortisol detection within 5 minutes through direct sweat collection. The application of this technology holds great potential in the field of personal health management, facilitating users to conveniently monitor their mental and physical conditions.

New Stable Gallium(III) and Indium(III) Complexes with Thiosemicarbazone Ligands: A Biological Evaluation.

The aim of this work is to explore a new library of coordination compounds for medicinal applications. Gallium is known for its various applications in this field. Presently, indium is not particularly important in medicine, but it shares a lot of chemical traits with its above-mentioned lighter companion, gallium, and is also used in radio imaging. These metals are combined with thiosemicarbazones, ligating compounds increasingly known for their biological and pharmaceutical applications. In particular, the few ligands chosen to interact with these hard metal ions share the ideal affinity for a high charge density. Therefore, in this work we describe the synthesis and the characterization of the resulting coordination compounds. The yields of the reactions vary from a minimum of 21% to a maximum of 82%, using a fast and easy procedure. Nuclear Magnetic Resonance (NMR) and Infra Red (IR) spectroscopy, mass spectrometry, elemental analysis, and X-ray Diffraction (XRD) confirm the formation of stable compounds in all cases and a ligand-to-metal 2:1 stoichiometry with both cations. In addition, we further investigated their chemical and biological characteristics, via UV-visible titrations, stability tests, and cytotoxicity and antibiotic assays. The results confirm a strong stability in all explored conditions, which suggests that these compounds are more suitable for radio imaging applications rather than for antitumoral or antimicrobic ones.

Effects of topically administered 0.6% hyaluronic acid on the healing of labial frenectomy in conventional and 940-nm indium gallium arsenide phosphide (InGaAsP) diode laser techniques in pediatric patients: a randomized, placebo-controlled clinical study.

This study aimed to investigate the effects of 0.6% hyaluronic acid (HA) gel on the healing process and postoperative pain levels after diode laser-assisted labial frenectomy in pediatric patients. Ninety-six pediatric patients (females, 50 and males, 46) aged 8-14 years were randomly divided into four groups as follows: (1) conventional frenectomy with 0.6% topically administered HA (CFH, n = 24); (2) conventional frenectomy with placebo gel (CFP, n = 24); (3) frenectomy performed by diode laser with 0.6% topically administered HA (DLH, n = 24); and (4) frenectomy performed by diode laser with placebo gel (DLP, n = 24). HA application was continued for 1 week thrice daily after the frenectomy. Visual analog scale forms were collected from patients 1 week after the operation. In addition, the plaque index, gingival index, periodontal probing depth, and keratinized tissue width and thickness were recorded. This process was repeated 1 and 3 months after the first visit. The DLH group revealed significant differences in the probing depth, bleeding on probing, keratinized gingiva width, and attached gingiva width according to dual comparisons of the initial, first, and third-month values (p = 0.010, p = 0.007, p<0.001, and p = 0.001, respectively). Significant differences were observed between the CFP and CFH groups according to the initial and initial third-month values with regard to the bleeding on probing (p=0.019 and p = 0.019, respectively). The attached gingival thickness revealed significant differences between the CFP and CFH groups for the initial and initial-third-month comparisons (p = 0.005 and p = 0.007, respectively). The mean values of the initial and initial-third-month differences were significantly higher in the CFH group than those in the CFP group. HA- and laser-assisted labial frenectomies revealed better outcomes in terms of the probing depth, attached gingiva width, keratinized gingiva width, healing process, and postoperative comfort.

Study on the behavior of clusters in the physical recovery of GaAs scrap.

Gallium arsenide (GaAs) is the most widely used second-generation semiconductor material. However, a large amount of GaAs scrap is generated at various stages of the GaAs wafer production process. Volatile GaAs clusters are inevitably generated during the process of GaAs vacuum thermal decomposition, resulting in lower purity of the recovered arsenic and the loss of gallium. In this study, thermodynamic analysis and dynamics simulation were combined to discuss the possibility of separating GaAs clusters and arsenic from a microscopic perspective. A vacuum thermal decomposition-directional condensation recovery process for GaAs scrap was proposed. By properly adjusting the separation parameters such as heating temperature, holding time and raw material size, high purity of gallium (99.99%) and arsenic (99.5%) were directly recovered under a system pressure of 1 Pa, heating temperature of 1323 K, holding time of 3 h, and GaAs scrap size of 2.5 cm. GaAs clusters were also recovered in powder form. The problem of difficult separation of GaAs clusters from arsenic was effectively solved by this method, and the purity of recovered arsenic was greatly improved. No additives are required and no waste liquid or gas emission in the whole process. The complexity of subsequent arsenic purification operations and the threat of arsenic containing waste to the environment were reduced as well.

Liquid Metal Nanocores Initiated Construction of Smart DNA-Polymer Microgels with Programmable and Regulable Functions and Near-Infrared Light-Driven Locomotion.

Due to their sequence-directed functions and excellent biocompatibility, smart DNA microgels have attracted considerable research interest, and the combination of DNA microgels with functional nanostructures can further expand their applications in biosensing and biomedicine. Gallium-based liquid metals (LMs) exhibiting both fluidic and metallic properties hold great promise for the development of smart soft materials; in particular, LM particles upon sonication can mediate radical-initiated polymerization reactions, thus allowing the combination of LMs and polymeric matrix to construct "soft-soft" materials. Herein, by forming active surfaces under sonication, LM nanoparticles (LM NPs) initiated localized radical polymerization reactions allow the combination of functional DNA units and different polymeric backbones to yield multifunctional core/shell microgels. The localized polymerization reaction allows fine control of the microgel compositions, and smart DNA microgels with tunable catalytic activities can be constructed. Moreover, due to the excellent photothermal effect of LM NPs, the resulting temperature gradient between microgels and surrounding solution upon NIR light irradiation can drive the oriented locomotion of the microgels, and remote control of the activity of these smart microgels can be achieved. These microgels may hold promise for various applications, such as the development of in vivo and in vitro biosensing and drug delivery systems.

Prediction of Acute Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy Using Dose-Volume Parameters From Functional Mapping on Gallium 68 Perfusion Positron Emission Tomography/Computed Tomography.

PURPOSE: The aim of this work was to compare anatomic and functional dose-volume parameters as predictors of acute radiation-induced lung toxicity (RILT) in patients with lung tumors treated with stereotactic body radiation therapy. METHODS AND MATERIALS: Fifty-nine patients treated with stereotactic body radiation therapy were prospectively included. All patients underwent gallium 68 lung perfusion positron emission tomography (PET)/computed tomography (CT) imaging before treatment. Mean lung dose (MLD) and volumes receiving x Gy (VxGy, 5-30 Gy) were calculated in 5 lung volumes: the conventional anatomic volume (AV) delineated on CT images, 3 lung functional volumes (FVs) defined on lung perfusion PET imaging (FV50%, FV70%, and FV90%; ie, the minimal volume containing 50%, 70%, and 90% of the total activity within the AV), and a low FV (LFV; LFV = AV - FV90%). The primary endpoint of this analysis was grade ≥2 acute RILT at 3 months as assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Dose-volume parameters in patients with and without acute RILT were compared. Receiver operating characteristic curves assessing the ability of dose-volume parameters to discriminate between patients with and without acute RILT were generated, and area under the curve (AUC) values were calculated. RESULTS: Of the 59 patients, 10 (17%) had grade ≥2 acute RILT. The MLD and the VxGy in the AV and LFV were not statistically different between patients with and without acute RILT (P > .05). All functional parameters were significantly higher in acute RILT patients (P < .05). AUC values (95% CI) for MLD AV, LFV, FV50%, FV70%, and FV90% were 0.66 (0.46-0.85), 0.60 (0.39-0.80), 0.77 (0.63-0.91), 0.77 (0.64-0.91), and 0.75 (0.58-0.91), respectively. AUC values for V20Gy AV, LFV, FV50%, FV70%, and FV90% were 0.65 (0.44-0.87), 0.64 (0.46-0.83), 0.82 (0.69-0.95), 0.81 (0.67-0.96), and 0.75 (0.57-0.94), respectively. CONCLUSIONS: The predictive value of PET perfusion-based functional parameters outperforms the standard CT-based dose-volume parameters for the risk of grade ≥2 acute RILT. Functional parameters could be useful for guiding radiation therapy planning and reducing the risk of acute RILT.

Simple preparation of lignosulfonate stabilized eutectic gallium/indium liquid metal nanodroplets through ball milling process.

The combination of biomass and liquid metal (LM) makes the preparation process "greener" and application of LM composite materials more sustainable. Here we reported the solvent free preparation of lignosulfonate (LS) stabilized eutectic gallium/indium (EGaIn) LM nanodroplets through ball milling (BM), which was recognized to be efficient and environmentally-friendly alternatives to solution-based methods. By regulating the BM frequency and milling time, uniform LM nanodroplets with a size <200 nm can be achieved. Moreover, the surface of the EGaIn nanodroplets was covered by LS molecules, owing to the hydrogen bond formed between Ga2O3 and LS. Hydrophilic LS shell endowed the LS@EGaIn nanodroplets excellent colloidal stability in the aqueous media. The elongation at break and fracture strength of hydrogel with the addition of LS@EGaIn significantly improved with the addition of LS@EGaIn. Besides, the conductivity and excellent stress responsibility of the LS@EGaIn composite hydrogel illustrated its potential application as s a stress sensor, flexible wearable devices and other related applications. Moreover, it was predicted that LS can be replaced by other synthesized or biological macromolecules, and induced the formation of types of LM based composite materials through such a simple method.

Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study.

PURPOSE: We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial. PATIENTS AND METHODS: Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis. RESULTS: MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; P < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; P < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% v 88.9%; P = .013) and at EOI (93.1% v 86.7%; P = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; P = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% v 16.0% in those receiving CHOP; P < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% v G-CHOP, 7.0%; R-CVP, 21.7% v G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse. CONCLUSION: MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.

Interaction of gallium, indium, and vanadyl curcumin complexes with hen egg-white lysozyme (HEWL): Mechanistic aspects and evaluation of antiamyloidogenic activity.

Many proteins and peptides can aggregate into amyloid fibrils with high-ordered and cross-ß rich structure characteristics. Amyloid deposition is a common feature of neurodegenerative diseases called amyloidosis. Various natural polyphenolic compounds such as curcumin exhibited antiamyloidogenic activities, but less researches were focused on the metal complexes of these compounds. In this study, the inhibitory effects of gallium curcumin (Ga(cur)3), indium curcumin (In(cur)3), and vanadyl curcumin (VO(cur)2) on the amyloid fibrillation of hen egg white lysozyme (HEWL) have been investigated. Moreover, the details of binding interactions of these metal complexes with HEWL have been explored. The results of fluorescence quenching analyses revealed that In(cur)3 and VO(cur)2 have much higher binding affinities than Ga(cur)3 toward HEWL. The interactions of these metal complexes were accompanied by partial conformational changes in the tertiary structure of HEWL. The kinetic curves of the fibrillation process demonstrated that In(cur)3 and VO(cur)2 have higher inhibitory effects than Ga(cur)3 on the amyloid fibrillation of HEWL. The strength of binding to HEWL is completely in accordance with inhibitory activities of these metal complexes of curcumin.

Novel lactoferrin-conjugated gallium complex to treat Pseudomonas aeruginosa wound infection.

Pseudomonas aeruginosa is one of the leading causes of opportunistic infections such as chronic wound infection that could lead to multiple organ failure and death. Gallium (Ga3+) ions are known to inhibit P. aeruginosa growth and biofilm formation but require carrier for localized controlled delivery. Lactoferrin (LTf), a two-lobed protein, can deliver Ga3+ at sites of infection. This study aimed to develop a Ga-LTf complex for the treatment of wound infection. The characterisation of the Ga-LTf complex was conducted using differential scanning calorimetry (DSC), Infra-Red (FTIR) and Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES). The antibacterial activity was assessed by agar disc diffusion, liquid broth and biofilm inhibition assays using the colony forming units (CFUs). The healing capacity and biocompatibility were evaluated using a P.aeruginosa infected wound in a rat model. DSC analyses showed thermal transition consistent with apo-lactoferrin; FTIR confirmed the complexation of gallium to lactoferrin. ICP-OES confirmed the controlled local delivery of Ga3+. Ga-LTf showed a 0.57 log10 CFUs reduction at 24 h compared with untreated control in planktonic liquid broth assay. Ga-LTf showed the highest antibiofilm activity with a 2.24 log10 CFUs reduction at 24 h. Furthermore, Ga-LTf complex is biocompatible without any adverse effect on brain, kidney, liver and spleen of rats tested in this study. Ga-LTf can be potentially promising novel therapeutic agent to treat pathogenic bacterial infections.

Metallic Gallium Droplets Exhibit Poor Antibacterial Properties.

The rise of antibiotic resistance in pathogenic bacteria requires new therapeutics to be developed. Several metallic nanoparticles such as those made from silver, copper, and zinc have shown significant antibacterial activity, in part due to metal ion leaching. Ga3+ containing compounds have also been shown to have antibacterial properties. Accordingly, it is estimated that metallic Ga droplets may be antibacterial, and some studies to date have confirmed this. Here, multiple concentrations of Ga droplets were tested against the antibiotic resistant Gram-positive bacteria methicillin-resistantStaphylococcus aureus (MRSA) and the Gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa) Despite a high concentration (2 mg/mL), Ga droplets had only modest antibacterial activity against both bacteria after 24 h of interaction. Finally, we demonstrated that Ga droplets were easily functionalized through a galvanic replacement reaction to develop antibacterial particles with copper and silver demonstrating a total detectable reduction of MRSA and >96% reduction ofP. aeruginosa. Altogether, these results contradict previous literature and show that Ga droplets demonstrate no antibacterial activity at concentrations comparable to those of conventional antibiotics and well-established antibacterial nanomaterials and only modest antibacterial activity at very high concentrations. However, we demonstrate that their antibacterial activity can be easily enhanced by functionalization.