LEIFR-Net: light estimation for implicit face relight network.

Relighting facial images based on estimated lighting distribution and intensity from image backgrounds and environments can lead to more natural and convincing effects across diverse settings. In this paper, we introduce the Light Estimation for Implicit Face Relight Network (LEIFR-Net), which we believe to be a novel approach that significantly improves upon current methodologies. Initially, we present a method to estimate global illumination from a single image. We then detail our approach for structurally disentangled relighting of faces using pixel-aligned implicit functions. Furthermore, we elaborate on constructing a paired synthetic dataset, which includes environments, maps of lighting distribution, albedo and relighted faces, utilizing a process we refer to as stable diffusion. Our experimental results, evaluated against specific benchmarks, demonstrate the effectiveness of LEIFR-Net in achieving more harmonious alignment of highlights and shadows with environmental lighting, surpassing the performance of other contemporary methods in this domain.

Superalkali-alkaline earthide ion pairs of δ+(AM-HMHC)-AM'δ- (AM = Li, Na and K; AM' = Be, Mg and Ca) possessing large NLO responses and excellent electronic stabilities and alkalide characteristics: a DFT study.

To identify superalkali-alkaline earthide ion pairs, it's theoretically shown that, as a novel class of excess electron superalkali compounds, both chair and boat forms of (AM-HMHC)-AM' (AM = Li, Na, and K; AM' = Be, Mg, and Ca; HMHC = 1,4,7,10,13,16-hexamethyl-1,4,7,10,13,16-hexaazacyclooctadecane) are good candidates. An attractive superalkali-alkaline earthide ion pair in δ+(AM-HMHC)-AM'δ- is firstly exhibited, which possesses alkaline-earthide characteristics and nonlinear optical response superior to similar M+(calix[4]pyrrole)M'- (M = Li, Na, and K; M' = Be, Mg, and Ca) with high stability. The electronic and vibrational second order hyperpolarizabilities and the frequency-dependent first hyperpolarizabilities of δ+(AM-HMHC)-AM'δ- are presented. For each pair of (AM-HMHC)-AM', the boat conformation is preferred to its chair one in the case of Hyper-Rayleigh scattering response (ßHRS). These alkaline earthides suggest prominently high ßHRS up to 2.59 × 104 a.u. (boat forms of δ+(Na-HMHC)-Caδ-). We expect that this work will inspire the preparation and characterization of these new alkaline earthides as high-performance NLO materials.

WormCNN-Assisted Establishment and Analysis of Glycation Stress Models in C. elegans: Insights into Disease and Healthy Aging.

Glycation Stress (GS), induced by advanced glycation end-products (AGEs), significantly impacts aging processes. This study introduces a new model of GS of Caenorhabditis elegans by feeding them Escherichia coli OP50 cultured in a glucose-enriched medium, which better simulates human dietary glycation compared to previous single protein-glucose cross-linking methods. Utilizing WormCNN, a deep learning model, we assessed the health status and calculated the Healthy Aging Index (HAI) of worms with or without GS. Our results demonstrated accelerated aging in the GS group, evidenced by increased autofluorescence and altered gene expression of key aging regulators, daf-2 and daf-16. Additionally, we observed elevated pharyngeal pumping rates in AGEs-fed worms, suggesting an addictive response similar to human dietary patterns. This study highlights the profound effects of GS on worm aging and underscores the critical role of computer vision in accurately assessing health status and aiding in the establishment of disease models. The findings provide insights into glycation-induced aging and offer a comprehensive approach to studying the effects of dietary glycation on aging processes.

Molecular Surveillance Detects High Prevalence of the Neglected Parasite Mansonella ozzardi in the Colombian Amazon.

BACKGROUND: Mansonellosis is an undermapped insect-transmitted disease caused by filarial nematodes that are estimated to infect hundreds of millions of people. Despite their prevalence, there are many outstanding questions regarding the general biology and health impacts of the responsible parasites. Historical reports suggest that the Colombian Amazon is endemic for mansonellosis and may serve as an ideal location to pursue these questions. METHODS: We deployed molecular and classical approaches to survey Mansonella prevalence among adults belonging to indigenous communities along the Amazon River and its tributaries near Leticia, Colombia. RESULTS: Loop-mediated isothermal amplification (LAMP) assays on whole-blood samples detected a much higher prevalence of Mansonella ozzardi infection (approximately 40%) compared to blood smear microscopy or LAMP performed using plasma, likely reflecting greater sensitivity and the ability to detect low microfilaremias and occult infections. Mansonella infection rates increased with age and were higher among men. Genomic analysis confirmed the presence of M. ozzardi that clusters closely with strains sequenced in neighboring countries. We successfully cryopreserved M. ozzardi microfilariae, advancing the prospects of rearing infective larvae in controlled settings. CONCLUSION: These data suggest an underestimation of true mansonellosis prevalence, and we expect that these methods will help facilitate the study of mansonellosis in endemic and laboratory settings.

Prognostic value of EBV DNA and platelet-to-lymphocyte ratio in patients with non-metastatic nasopharyngeal carcinoma: a retrospective study.

PURPOSE: Analyzing the prognostic value of Epstein-Barr virus (EBV) DNA load and platelet-to-lymphocyte ratio (PLR) in non-metastatic nasopharyngeal carcinoma (NPC) patients, thereby developing a reliable and effective marker. METHODS: We compared survival rates among different groups using the Kaplan-Meier method and the Log-rank test. The factors affecting the prognosis of NPC patients were determined using univariate and multivariate cox regression analysis. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. RESULTS: The ROC curve indicated a cut-off value of 775 copies/ml for EBV DNA and 203.3 for PLR. Kaplan-Meier and Log-rank tests showed that 3-year overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) of NPC patients in high risk group (HRG) were significantly poorer than those in medium risk group (MRG) and low risk group (LRG). The 3-year OS of NPC patients was significantly correlated with age, N stage and EBV DNA-PLR. The 3-year LRFS were significantly correlated with sex, N stage, histology type, and EBV DNA-PLR. The 3-year DMFS were correlated with histology type. The ROC curve showed that area under the curve (AUC) values of EBV DNA-PLR of 3-year OS, LRFS and DMFS in NPC were higher than those of PLR and EBV DNA. CONCLUSION: EBV DNA-PLR is an independent risk factor for the prognosis of NPC. Compared with PLR or EBV DNA alone, the combination of EBV DNA and PLR may be more accurate in predicting the prognosis of NPC patients.

Metalloborospherenes with a Stabilized Classical Fullerene-like Borospherene B40 Act as Nonlinear Optical Switches, Electron Reservoirs, Molecular Capacitors, and Molecular Reactors.

Using a new method of η5-Li and η6-Mg atoms capping the faces of the classical fullerene-like borospherene Td B40, we theoretically predict an exohedral metalloborospherene Td Mg10Li12&B40 molecule. Remarkably, a newfangled endoexo cage isomerism is proposed. Further, embedding Mg atoms in the Td B40 cage forms endohedral derivatives. Due to the intramolecular pull-push electron transfer relay, these obtained molecules possess unequal multilayered and alternant spherical charge distribution. The outer is an excess electron layer, bringing a molecular nonlinear switch character and an electron reservoir behavior with strong electron-donating and -accepting abilities. The middle (Mg2+)10(Li+)12 and the outer layers together constitute an electric double layer, presenting the behavior of a molecular capacitor where the electronic charge-discharge process occurs in the outer excess electron layer. The inner part is an empty cage B4026- with a strong negative electric field. The valence electrons of the embedded Mg atoms are transformed into new excess electrons and added in the outer excess electron layer, also exhibiting the charging behavior of the molecular capacitor. Considering the chemical reaction in the inner cage, the embedded Mg atom is ionized, forming an Mg2+ cation and 2e under the strong negative electric field; meanwhile, 2e is powerfully pushed into the outer excess electron layer. This chemical process shows a generalized Coulomb explosion, and thus the exohedral metalloborospherene molecules with cage B4026- may act as molecular reactors. The new species mark the genesis of classical fullerene-like borospherene chemistry and stimulate their applications in molecular nonlinear optical and nanoelectronics.

Comparing the efficacy and safety of cisplatin and other platinum-based chemotherapies in locally advanced nasopharyngeal carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cisplatin-based concurrent chemoradiotherapy has been identified as the primary and standard treatment for locally advanced nasopharyngeal carcinoma (NPC). However, the side effects of cisplatin affect the compliance to therapy. Thus, the search for a platinum-based substitute for NPC has always been a research focus. However, there is a variability in the efficacy of different platinum-based chemotherapies in the treatment of NPC. We performed a meta-analysis to compare the efficacy and safety of cisplatin-based regimens and other platinum-based derivatives (carboplatin, nedaplatin, and lobaplatin) for locally advanced NPC. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov were systematically searched for all potentially eligible clinical trials as of February 15, 2022. The pooled hazard ratios, risk ratio, and 95% confidence interval were calculated using Review Manager Software version 5.4. RESULTS: A total of 1,907 patients with locally advanced NPC were eligible from the 1,265 retrieved records. This systematic review included eight articles, six of which were randomized controlled clinical trials. There was no significant difference in the 3- and 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival between cisplatin-based chemotherapy and other platinum-based chemotherapy. Severe acute hematological side effects (≥ grade 3) during treatment, such as neutropenia, leukopenia, and thrombocytopenia, were equivalent in both groups. However, the incidence of anemia was higher in patients receiving other platinum-based chemotherapies. The risk of nausea, vomiting and weight loss was higher in the cisplatin group; however, there was no significant difference in the other non-hematological and late side effects between the two groups. CONCLUSIONS: Other types of platinum-based chemotherapies are as effective as cisplatin-based chemotherapy in the treatment of locally advanced NPC, thus acting as potential alternatives to cisplatin. Further studies providing high-level evidence are needed.

High electron affinity triggered by lithium coordination: quasi-chalcogen properties of Li2Sn8Be.

This work puts forward an unusual but rational strategy to design superatoms mimicking the properties of group via elements. A new dianion with closo-configuration, namely Li2Sn8Be2-, has been obtained by decorating endohedral Zintl ion Sn8Be4- with two Li ligands. Its neutral counterpart, namely Li2Sn8Be, exhibits a high electron affinity of 2.526 eV, which not only exceeds that of the Sn8Be cluster but is higher than those of chalcogen elements. Li2Sn8Be has the potential to form stable ionic compounds with lithium, calcium, and even superalkali and superalkali-earth-metal atoms, and has an oxidation state of -2 therein. Besides, compound analogues of CO, O22-, H2O2, and Li2O2 can also be obtained with Li2Sn8Be serving as the building block. The striking resemblance between Li2Sn8Be and oxygen-group elements not only qualifies it for membership of the superatom family, but further collaborates the theoretical framework of the "three-dimensional periodic table".

Can a molecular switch exist in both superalkali electride and superalkalide forms?

To combine both electride and alkalide characteristics in one molecular switch, it is shown herein that the phenalenyl radical and the M3 ring (M3-PHY, M = Li, Na, and K) stacked with parallel and vertical geometries are good candidates. The former geometry is the superalkali electride e-⋯M3+-PHY while the latter geometry is the superalkalide Mδ--M2(1-δ)+-PHY-. The superalkalide Mδ--M2(1-δ)+-PHY- may isomerize to the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K) using suitable long-wavelength irradiation, while the latter may isomerize to the former with suitable short-wavelength irradiation. Also, applying suitable oriented external electric fields can drive the superalkalide Mδ-M2(1-δ)+-PHY- to change into the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K). The differences in the static and dynamic first hyperpolarizability (ß0) values between them were also studied.

On Close Parallels between the Zintl-Based Superatom Ge9Be and Chalcogen Elements.

Ever since the concept of superatoms was brought forward in the 1990s, various specific types of clusters have been proposed to mimic atomic properties and enrich the "three-dimensional periodic table". In this work, a Zintl cluster, namely, Ge9Be, has been certified eligible to join the superatom family, owing to its surprising similarity to chalcogen elements. Having 38 valence electrons, Ge9Be has an intrinsic desire to gain two additional electrons to achieve electronic shell closure, in which its quasi-chalcogen identity roots. Like oxygen-group elements, Ge9Be has the potential to form stable ionic compounds with lithium, beryllium, calcium, and superalkaline-earth atom FLi3. On the other hand, the combination of Ge9Be and the multiple valence superatom Al7- results in covalent compounds resembling carbon oxides. Close parallels have also been found between (Ge9Be)2-based compounds and common peroxides, further evidencing the superatom characteristics of Ge9Be. This finding puts forward an almost perfect superatom counterpart of group VIA elements and opens the door to characteristics-oriented design and synthesis of stable superatom motifs by utilizing solid Zintl clusters.

Switching from an electride-like molecule to the molecular electride K-F6C6H6 driven by an oriented external electric field.

The exploration of innovative molecular switches has resulted in large developments in the field of molecular electronics. Focusing on a single molecular switch with different forms exhibiting different electride features, potassium-atom-doped all-cis 1,2,3,4,5,6-hexafluorocyclohexane K-F6C6H6 was studied theoretically. It was found that an oriented external electric field can drive excess electron transfer from the region outside of the K atom to that outside of F6C6H6. Subsequently, the electride-like molecule K-F6C6H6 (1) switches into the molecular electride K-F6C6H6e- (3) through another electride-like molecule K-F6C6H6 (2). The static first hyperpolarizabilities (ß0) are increased over 12- and 5-fold when moving from 1 to 2 and 3, respectively. The rise of each ß0 value constitutes an order of magnitude improvement. Between them, the different ß0 values suggest that K-F6C6H6 is a good candidate for use as a multiple-response nonlinear optics switch. The order of the ß0 values of 1-4 for M-F6C6H6 (M = Li and Na) coincide with that of K-F6C6H6, also exhibiting a switch effect.

Distinctive Characteristics of Al7Li: A Superatom Counterpart of Group IVA Elements.

A new superatom of dual valence states, namely Al7Li, has been proposed to further enrich the "three-dimensional periodic table". It bears great resemblance to group IVA elements in many aspects. Chief among them is that Al7Li favors both +2 and +4 oxidation states, which makes it analogous to the heavier carbon-group elements. Al7Li is capable of forming stable ionic compounds with carbon, oxygen, and fluorine and forming covalent tetrahydride with hydrogen, just as how germanium, tin, and lead atoms combine with these elements to form stable molecules. The nearest atomic counterpart of Al7Li in group IV is probably Sn or Pb since their oxides and tetrahydrides share like characteristics.

Novel inorganic aromatic mixed-valent superalkali electride CaN3Ca: an alkaline-earth-based high-sensitivity multi-state nonlinear optical molecular switch.

Focusing on innovative high-performance single-pole double-throw nonlinear optical (NLO) molecular switches, two C3v configurations (1 and 3) and one D3h configuration (2) of bipyramidal CaN3Ca have been obtained by using quantum mechanical methods. Not only are 1, 2, and 3 alkaline-earth-based aromatic superalkalis, but they are also interesting electrides. The salt-like electronic structures of e-Ca2+N33-Ca2+ (1) and Ca2+N33-Ca2+e- (3) with localized redox centres are rare inorganic Robin-Day class II-type structures, and e0.5-Ca2+N33-Ca2+e0.5- (2) with a delocalized structure is a class III-type mixed-valent superalkali electride. Under a small external electric field of ±0.0110 a.u. (0.565 V Å-1), the short-distance hopping of Ca atoms in CaN3Ca from the D3h configuration with in-plane aromaticity to each C3v configuration with out-of-plane aromaticity brings about the long-range transfer of half an electron from one Ca atom to another. And, subsequently, a large dipole moment (µ0) and remarkable static first hyperpolarizability (ß0) occur. µz and ßzzz range from 0 (D3h, off form) to -12.1 or 12.1 D (C3v, on forms) and from 0 (D3h, off form) to -19 428 or 19 428 a.u. (C3v, on forms), respectively. These extremely large differences in µz and ßzzz values between the D3h and each of the C3v configurations confirm the potential of these inorganic aromatic Robin-Day-type superalkali electrides for applications in high-sensitivity multi-state nonlinear optical switches.

Coinage metalides: a new class of excess electron compounds with high stability and large nonlinear optical responses.

The possibility of using coinage metal atoms as excess electron acceptors is examined for the first time by designing a new class of M+-1-M'- (M = Li, Na, and K; M' = Cu, Ag, and Au) compounds termed "coinage metalides" on the basis of an intriguing Janus-type all-cis1,2,3,4,5,6-hexafluorocyclohexane (1) molecule. Under the large facial polarization of 1, the outermost ns1 electrons of alkali metal atoms can be transferred to coinage metal atoms, forming diffuse excess electrons around them. Consequently, the resulting M+-1-Cu- and M+-1-Ag- compounds exhibit significantly large nonlinear optical (NLO) responses. In particular, these novel M+-1-M'- compounds exhibit much higher stability (larger VIEs and Ec values) than that of the corresponding M+·1·M'- (M, M' = Li, Na, and K) alkalides. We hope this work could open up new possibilities for NLO material design by using coinage metal atoms as excess electron acceptors and, on the other hand, attract more experimental interest and efforts to synthesize such stable compounds in the laboratory.

Electric field induced intra-molecular self-redox: superalkali Li3N3Mg as a candidate for NLO molecular switches.

A novel intra-molecular self-redox switch, Li3N3Mg, is constructed theoretically. Our investigation showed that a suitably oriented external electric field (OEEF) can drive a long-range excess electron transfer from Mg atoms to Li3 rings. And subsequently, an interesting intra-molecular self-redox from Li32+N33-Mg+ to Li3+N33-Mg2+ accompanying the large different electronic static first hyperpolarizability (ß) is exhibited. The increase of the ß value constitutes an order of magnitude improvement from Li32+N33-Mg+ (34 986 a.u.) to Li3+N33-Mg2+ (101 225 a.u.), which indicates that Li3N3Mg is a good candidate for a self-redox NLO molecular switch.

Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model.

BACKGROUND: During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threats to human health and major efforts have been undertaken to better understand the host-pathogen interactions that eventually determine the outcome of the infection. Over the last decades, the unicellular eukaryote Dictyostelium discoideum has become an established infection model, serving as a surrogate macrophage that can be infected with a wide range of intracellular pathogens. In this study, we use high-throughput RNA-sequencing to analyze the transcriptional response of D. discoideum when infected with Mycobacterium marinum and Legionella pneumophila. The results were compared to available data from human macrophages. RESULTS: The majority of the transcriptional regulation triggered by the two pathogens was found to be unique for each bacterial challenge. Hallmark transcriptional signatures were identified for each infection, e.g. induction of endosomal sorting complexes required for transport (ESCRT) and autophagy genes in response to M. marinum and inhibition of genes associated with the translation machinery and energy metabolism in response to L. pneumophila. However, a common response to the pathogenic bacteria was also identified, which was not induced by non-pathogenic food bacteria. Finally, comparison with available data sets of regulation in human monocyte derived macrophages shows that the elicited response in D. discoideum is in many aspects similar to what has been observed in human immune cells in response to Mycobacterium tuberculosis and L. pneumophila. CONCLUSIONS: Our study presents high-throughput characterization of D. discoideum transcriptional response to intracellular pathogens using RNA-seq. We demonstrate that the transcriptional response is in essence distinct to each pathogen and that in many cases, the corresponding regulation is recapitulated in human macrophages after infection by mycobacteria and L. pneumophila. This indicates that host-pathogen interactions are evolutionary conserved, derived from the early interactions between free-living phagocytic cells and bacteria. Taken together, our results strengthen the use of D. discoideum as a general infection model.

On the Possibility of Using the Jellium Model as a Guide To Design Bimetallic Superalkali Cations.

The potential application of the jellium model as guidance in the rational design of bimetallic superalkali cations is examined under gradient-corrected density functional theory for the first time. By using Li, Mg, and Al as atomic building blocks, a series of bimetallic cationic clusters with 2, 8, 20, and 40 valence electrons are obtained and investigated. As the corresponding neutral clusters tend to lose one valence electron to achieve closed-shell states in the jellium model, these studied cations exhibit much lower vertical electron affinities (EAvert , 3.42-4.95 eV) than the ionization energies (IEs) of alkali metal atoms, indicating their superalkali identities. The high stability of these cationic clusters is guaranteed by their considerable HOMO-LUMO gaps and binding energies per atom. Moreover, the feasibility of using the designed superalkalis as efficient reductants to activate CO2 and N2 molecules and as stable building blocks to assemble ionic superatom compounds is explored. Therefore, this study may provide an effective method for obtaining various metallic superatoms with extensive applications on the basis of the simple jellium rule.

Boron-Substituted Coronene: Intriguing Geometric and Electronic Properties, and Large Nonlinear Optical Response.

By substituting boron atoms for selected carbon atoms of a graphene quantum dot (GQD) model, namely a coronene molecule, the substituent effect on its geometric and electronic structure, as well as nonlinear optical response has been systemically investigated in theory. Our computations reveal that the boron substitution leads to a similar noncentrosymmetric apophysis structure for the boron-substituted coronene in singlet and triplet states. Noticeably, due to the small energy difference of 2.5 kcal mol-1 between the singlet and triplet states, the boron-substituted molecule can easily be switched between the antiferromagnetic (singlet state) and ferromagnetic (triplet state) state by slightly changing the external conditions. Notably, the boron-substituted coronene exhibits a considerably large first hyperpolarizability of 36241 au, because boron substitution yields a raised structure with an intermediate singlet diradical character. Hence, it is expected that this study not only provides new insights for the boron-substituent effect on the structure and properties of graphene but also may promote practical applications of GQDs in the fields of spintronics and nonlinear optics.

Can Coinage Metal Atoms Be Capable of Serving as an Excess Electron Source of Alkalides with Considerable Nonlinear Optical Responses?

Alkalides, as a representative kind of excess electron compounds, have been demonstrated to be potential nonlinear optical (NLO) materials with large static first hyperpolarizabilities (ß0). The possibility of utilizing coinage metal atoms as a novel excess electron source to design a series of alkalides, i.e., (M@36adz)M' (M = Cu, Ag, and Au; M' = Li, Na, and K), was examined by density functional theory calculations. The alkalide characteristics of these compounds are guaranteed by their HOMOs and VIE values as well as NBO analysis. In particular, all proposed alkalides exhibit considerable first hyperpolarizabilities (ß0) up to 61 590 au, indicating that they can be considered as novel NLO molecules of high performance. Moreover, a larger cage-complexant has been considered, and the resulting (Ag+@TriPip222)K- alkalide possesses a remarkably large ß0 value of 180 068 au. We hope that this work will provide a new recipe for designing excess electron compounds and, on the other hand, attract more research interest and efforts in exploring new, unconventional alkalides.

Structure of the trehalose-6-phosphate phosphatase from Brugia malayi reveals key design principles for anthelmintic drugs.

Parasitic nematodes are responsible for devastating illnesses that plague many of the world's poorest populations indigenous to the tropical areas of developing nations. Among these diseases is lymphatic filariasis, a major cause of permanent and long-term disability. Proteins essential to nematodes that do not have mammalian counterparts represent targets for therapeutic inhibitor discovery. One promising target is trehalose-6-phosphate phosphatase (T6PP) from Brugia malayi. In the model nematode Caenorhabditis elegans, T6PP is essential for survival due to the toxic effect(s) of the accumulation of trehalose 6-phosphate. T6PP has also been shown to be essential in Mycobacterium tuberculosis. We determined the X-ray crystal structure of T6PP from B. malayi. The protein structure revealed a stabilizing N-terminal MIT-like domain and a catalytic C-terminal C2B-type HAD phosphatase fold. Structure-guided mutagenesis, combined with kinetic analyses using a designed competitive inhibitor, trehalose 6-sulfate, identified five residues important for binding and catalysis. This structure-function analysis along with computational mapping provided the basis for the proposed model of the T6PP-trehalose 6-phosphate complex. The model indicates a substrate-binding mode wherein shape complementarity and van der Waals interactions drive recognition. The mode of binding is in sharp contrast to the homolog sucrose-6-phosphate phosphatase where extensive hydrogen-bond interactions are made to the substrate. Together these results suggest that high-affinity inhibitors will be bi-dentate, taking advantage of substrate-like binding to the phosphoryl-binding pocket while simultaneously utilizing non-native binding to the trehalose pocket. The conservation of the key residues that enforce the shape of the substrate pocket in T6PP enzymes suggest that development of broad-range anthelmintic and antibacterial therapeutics employing this platform may be possible.