Biosynthetic production of anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies.

Heparin is an important anticoagulant drug, and microbial heparin biosynthesis is a potential alternative to animal-derived heparin production. However, effectively using heparin synthesis enzymes faces challenges, especially with microbial recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, we introduce the monosaccharide N-trifluoroacetylglucosamine into Escherichia coli K5 to facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform is used to enhance sulfotransferase efficiency, resulting in the engineered NST-M8 enzyme with significantly improved stability (11.32-fold) and activity (2.53-fold) compared to the wild-type N-sulfotransferase. This approach can be applied to engineering various sulfotransferases. The multienzyme cascade reaction enables the production of active heparin from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) and anti-FIIa (48.62 IU/mg) activities. This study offers insights into overcoming challenges in heparin synthesis and modification, paving the way for the future development of animal-free heparins using a cellular system-based semisynthetic strategy.

Machine-Learning-Assisted Discovery of Mechanosynthesized Lead-Free Metal Halide Perovskites for the Oxidative Photocatalytic Cleavage of Alkenes.

Lead-free metal halide perovskites can potentially be air- and water-stable photocatalysts for organic synthesis, but there are limited studies on them for this application. Separately, machine learning (ML), a critical subfield of artificial intelligence, has played a pivotal role in identifying correlations and formulating predictions based on extensive datasets. Herein, an iterative workflow by incorporating high-throughput experimental data with ML to discover new lead-free metal halide perovskite photocatalysts for the aerobic oxidation of styrene is described. Through six rounds of ML optimization guided by SHapley Additive exPlanations (SHAP) analysis, BA2CsAg0.95Na0.05BiBr7 as a photocatalyst that afforded an 80% yield of benzoic acid under the standard conditions is identified, which is a 13-fold improvement compared to the 6% with when using Cs2AgBiBr6 as the initial photocatalyst benchmark that is started. BA2CsAg0.95Na0.05BiBr7 can tolerate various functional groups with 22 styrene derivatives, highlighting the generality of the photocatalytic properties demonstrated. Radical scavenging studies and density functional theory calculations revealed that the formation of the reactive oxygen species superoxide and singlet oxygen in the presence of BA2CsAg0.95Na0.05BiBr7 are critical for photocatalysis.

Model-data-driven adversarial active learning for brain tumor segmentation.

Active learning (AL) attempts to select informative samples in a dataset to minimize the number of required labels while maximizing the performance of the model. Current AL in segmentation tasks is limited to the expansion of popular classification-based methods including entropy, MC-dropout, etc. Meanwhile, most applications in the medical field are simply migrations that fail to consider the nature of medical images, such as high class imbalance, high domain difference, and data scarcity. In this study, we address these challenges and propose a novel AL framework for medical image segmentation task. Our approach introduces a pseudo-label-based filter addressing excessive blank patches in medical abnormalities segmentation tasks, e.g., lesions, and tumors, used before the AL selection. This filter helps reduce resource usage and allows the model to focus on selecting more informative samples. For the sample selection, we propose a novel query strategy that combines both model impact and data stability by employing adversarial attack. Furthermore, we harness the adversarial samples generated during the query process to enhance the robustness of the model. The experimental results verify our framework's effectiveness over various state-of-the-art methods. Our proposed method only needs less than 14% annotated patches in 3D brain MRI multiple sclerosis (MS) segmentation tasks and 20% for Low-Grade Glioma (LGG) tumor segmentation to achieve competitive results with full supervision. These promising outcomes not only improve performance but alleviate the time burden associated with expert annotation, thereby facilitating further advancements in the field of medical image segmentation. Our code is available at https://github.com/HelenMa9998/adversarial_active_learning.

Advancements in heparosan production through metabolic engineering and improved fermentation.

Heparin is one of the most widely used natural drugs, and has been the preferred anticoagulant and antithrombotic agent in the clinical setting for nearly a century. Heparin also shows increasing therapeutic potential for treating inflammation, cancer, and microbial and viral diseases, including COVID-19. With advancements in synthetic biology, heparin production through microbial engineering of heparosan offers a cost-effective and scalable alternative to traditional extraction from animal tissues. Heparosan serves as the starting carbon backbone for the chemoenzymatic synthesis of bioengineered heparin, possessing a chain length that is critically important for the production of heparin-based therapeutics with specific molecular weight (MW) distributions. Recent advancements in metabolic engineering of microbial cell factories have resulted in high-yield heparosan production. This review systematically analyzes the key modules involved in microbial heparosan biosynthesis and the latest metabolic engineering strategies for enhancing production, regulating MW, and optimizing the fermentation scale-up of heparosan. It also discusses future studies, remaining challenges, and prospects in the field.

Fine tuning of porphyrin based-paddlewheel framework by imidazole derivative to boost electrochemiluminescence performance.

Precise tuning the structure of catalytic center is of great importance for the construction of enhanced electrochemiluminescence (ECL) emitters and the development of ECL amplification strategies, which is a key factor in improving the sensitivity of biosensors. In this work, we report the enhanced ECL emitters based on the porphyrin-based paddlewheel framework (PPF) with axial coordinated imidazole-like ligands (PPF/X, X = 2-methylimidazole (MeIm), imidazole (Im), benzimidazole (BIM)). In this system, the electron-donating ability of the axial ligands is positively correlated to its coordination ability to the paddlewheel units and the catalytic ability of the axially coordinated paddlewheel units. In addition, the electrochemical and ECL behavior of PPF/X (X = MeIm, Im, BIM) with different axial coordinated ligands are explored.

Molecular characteristics of gastric cancer with ERBB2 amplification.

Gastric cancer is a prevalent malignancy with a high degree of heterogeneity, which has led to a poor therapeutic response. Though there are numerous HER2-targeted medicines for HER2+ gastric cancer, many trials have not indicated an improvement in overall survival. Here 29 ERBB2 amplification (ERBB2-Amp) type gastric cancer samples with WES and RNA-seq data were selected for investigation, which copy-number aberration (CNA) was +2. Initially, the somatic mutation and copy number variant (CNV) of them, which might cause resistance to HER2-targeted therapies, were systematically investigated evaluated, as well as their mutation signatures. Moreover, 37 modules were identified using weighted gene co-expression network analysis (WGCNA), including the blue module related to DFS status and lightcyan module correlated with ARHGAP26_ARHGAP6_CLDN18 rearrangement. In addition, focal adhesion and ECM-receptor interaction pathways were considerably enriched in the turquoise module with ERBB2 gene. ExportNetworkToCytoscape determined that MIEN1 and GRB7 are tightly connected to ERBB2., Finally, 14 single-cell intestinal gastric cancer samples were investigated, and it was shown that the TFAP2A transcription factor regulon was highly expressed in ERBB2high group, as was the EMT score. Overall, our data provide comprehensive molecular characteristics of ERBB2-Amp type gastric cancer, which offers additional information to improve HER2-targeted gastric cancer treatment.

Cell-Based Assay Approaches for Glycosaminoglycan Synthase High-Throughput Screening: Development and Applications.

Glycosaminoglycan synthases have immense potential in applications involving synthesis of oligosaccharides, using enzymatic approaches and construction of cell factories that produce polysaccharides as critical metabolic components. However, the use of high-throughput activity assays to screen for the evolution of these enzymes can be challenging because there are no significant changes in fluorescence or absorbance associated with glycosidic bond formation. Here, using incorporation of azido-labeled N-acetylhexosamine analogs into bacterial capsule polysaccharides via bacterial metabolism and bioorthogonal chemistry, fluorophores were specifically introduced onto cell surfaces. Furthermore, correlations between detectable fluorescence signals and the polysaccharide-synthesizing capacity of individual bacteria were established. Among 10 candidate genes, 6 members of the chondroitin synthase family were quickly identified in a recombinant Bacillus subtilis host strain. Additionally, directed evolution of heparosan synthase was successfully performed using fluorescence-activated cell sorting of recombinant Escherichia coli O10:K5(L):H4, yielding several mutants with increased activity. Cell-based approaches that selectively detect the presence or absence of synthases within an individual colony of bacterial cells, as well as their level of activity, have broad potential in the exploration and engineering of glycosaminoglycan synthases. These approaches also support the creation of novel strategies for high-throughput screening of enzyme activity based on cell systems.

Post-synthetic modification-driven ZIF reconstruction and functionalization for efficient SARS-CoV-2 ECL detection.

The emergence of novel pathogens, as well as their frequent variants, raises the significance of developing superior and versatile sensing materials and techniques. Herein, a post-modified zeolitic imidazolate framework (pm-ZIF) was synthesized by using ZIF-67 as a parent MOF, and zinc(II) meso-tetra (4-carboxyphenyl) porphine (ZnTCPP) as a successive exchange ligand. Due to the preservation of the tetrahedral Co-N4 units from the ZIF precursor and the introduced porphyrin luminophores, this hybrid material pm-ZIF/P(Zn) enables the linear electrochemiluminescence (ECL) signal conversion of the target DNA concentration. An efficient biosensor that can be used to quantitatively detect SARS-CoV-2 was therefore constructed. The linear range of the sensor was 10-12-10-8 M, with a limit of detection (LOD) reaching 158 pM. Compared with the traditional amplification-based methods, the duration time of our method is significantly shortened and the quantitation of the SARS-Cov-2 RdRp gene can be completed within twenty minutes at room temperature.

Novel ß1,4 N-acetylglucosaminyltransferase in de novo enzymatic synthesis of hyaluronic acid oligosaccharides.

The efficiency of de novo synthesis of hyaluronic acid (HA) using Pasteurella multocida hyaluronate synthase (PmHAS) is limited by its low catalytic activity during the initial reaction steps when monosaccharides are the acceptor substrates. In this study, we identified and characterized a ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) derived from the O-antigen gene synthesis cluster of Escherichia coli O8:K48:H9. Recombinant ß1,4 EcGnT effectively catalyzed the production of HA disaccharides when the glucuronic acid monosaccharide derivative 4-nitrophenyl-ß-D-glucuronide (GlcA-pNP) was used as the acceptor. Compared with PmHAS, ß1,4 EcGnT exhibited superior N-acetylglucosamine transfer activity (~ 12-fold) with GlcA-pNP as the acceptor, making it a better option for the initial step of de novo HA oligosaccharide synthesis. We then developed a biocatalytic approach for size-controlled HA oligosaccharide synthesis using the disaccharide produced by ß1,4 EcGnT as a starting material, followed by stepwise PmHAS-catalyzed synthesis of longer oligosaccharides. Using this approach, we produced a series of HA chains of up to 10 sugar monomers. Overall, our study identifies a novel bacterial ß1,4 N-acetylglucosaminyltransferase and establishes a more efficient process for HA oligosaccharide synthesis that enables size-controlled production of HA oligosaccharides. KEY POINTS: • A novel ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) from E. coli O8:K48:H9. • EcGnT is superior to PmHAS for enabling de novo HA oligosaccharide synthesis. • Size-controlled HA oligosaccharide synthesis relay using EcGnT and PmHAS.

Effects of the timing of epibrassinolide spraying on yield and nitrogen use efficiency of wide-belt sowing wheat.

In this study, we investigated the effects of epibrassinolide spraying at different growth stages on grain yield and nitrogen use efficiency (NUE), and uptake efficiency (UPE) of wide-belt sowing wheat. The results showed that epibrassinolide spraying enhanced wheat grain yield by increasing the number of kernels per spike and (or) 1000-kernel weight, and improved NUE by promoting aboveground nitrogen accumulation and improving UPE. However, the magnitudes of such enhancements in yield and NUE differed among spraying times. Spraying epibrassinolide at the erecting and filling stages, jointing and filling stages, erecting, jointing, and filling stages, as well as erecting, flowering, and filling stages, produced the greatest increase in the number of kernels per spike and 1000-kernel weight, which led to substantial yield increases (12.8%-14.0%), and the greatest increase in aboveground nitrogen accumulation, which improved UPE by 16.4%-18.8%, and resulted in a significant improvement in NUE. Therefore, spraying epibrassinolide at the erecting and filling stage or jointing and filling stages could achieve high yield and NUE in wide-belt sowing wheat.

Imaging of Escherichia coli K5 and glycosaminoglycan precursors via targeted metabolic labeling of capsular polysaccharides in bacteria.

The introduction of unnatural chemical moieties into glycosaminoglycans (GAGs) has enormous potential to facilitate studies of the mechanism and application of these critical, widespread molecules. Unnatural N-acetylhexosamine analogs were metabolically incorporated into the capsule polysaccharides of Escherichia coli and Bacillus subtilis via bacterial metabolism. Targeted metabolic labeled hyaluronan and the precursors of heparin and chondroitin sulfate were obtained. The azido-labeled polysaccharides (purified or in capsules) were reacted with dyes, via bioorthogonal chemistry, to enable detection and imaging. Site-specific introduction of fluorophores directly onto cell surfaces affords another choice for observing and quantifying bacteria in vivo and in vitro. Furthermore, azido-polysaccharides retain similar biological properties to their natural analogs, and reliable and predictable introduction of functionalities, such as fluorophores, onto azido-N-hexosamines in the disaccharide repeat units provides chemical tools for imaging and metabolic analysis of GAGs in vivo and in vitro.

Comparison of the efficacy of three types of Kirschner wire tension bands for ulnar olecranal fracture / 中国骨伤

OBJECTIVE@#To compare the clinical effect of three types of Kirschner wire tension band for olecranon fracture.@*METHODS@#The clinical data of 64 patients with olecranon fracture treated by Kirschner wire tension band fixation from March 2016 to May 2020 were retrospectively analyzed. Among them, 19 patients were treated with intramedullary K-wires fixation(group A) including 8 males and 11 females with an average of (48.2±18.3) years old, 3 patients were typeⅠ, and 16 patients were typeⅡ according to Mayo classification;20 patients were treated with transcortical K-wires fixation (group B) including 13 males and 7 females with an average of (43.5±20.4) years old, 3 patients were typeⅠand 17 patients were typeⅡ according to Mayo classification;25 patients were treated with perforated Kirschner wire(group C) including 15 males and 10 females with an average of (55.2±17.5) years old, 4 patients were typeⅠand 21 patients were typeⅡ according to Mayo classification. The operative time, intraoperative blood loss, times of Intraoperative fluoroscopy, fracture healing time and complications of 3 groups were compared. At the final follow-up, elbow function was assessed using the Mayo Elbow Function Scale.@*RESULTS@#There were differences in operative time, intraoperative fluoroscopy times, postoperative VAS and soft tissue irritation among the three groups(P<0.05). The operative time, intraoperative fluoroscopy times in group A and C was better than that in group B. The postoperative VAS score, skin irritability in group C was better than that of group B. The difference was statistically significant on Mayo elbow function score at the final follow-up among three groups(P<0.05), the scores of group A and C were higher than that of group B.@*CONCLUSION@#Compared with transcortical K-wires screw fixation, both intramedullary K-wires screw fixation and perforated Kirschner wire fixation, which can significantly reduce the occurrence of soft tissue irritation, reduce surgical complications and shorten the operation time.

2D Zn-Porphyrin-Based Co(II)-MOF with 2-Methylimidazole Sitting Axially on the Paddle-Wheel Units: An Efficient Electrochemiluminescence Bioassay for SARS-CoV-2.

High electrocatalytic activity with tunable luminescence is crucial for the development of electrochemiluminescence (ECL) luminophores. In this study, a porphyrin-based heterobimetallic 2D metal organic framework (MOF), [(ZnTCPP)Co2(MeIm)] (1), is successfully self-assembled from the zinc(II) tetrakis(4-carboxyphenyl)porphine (ZnTCPP) linker and cobalt(II) ions in the presence of 2-methylimidazole (MeIm) by a facile one-pot reaction in methanol at room temperature. On the basis of the experimental results and the theoretical calculations, the MOF 1 contains paddle-wheel [Co2(-CO2)4] secondary building units (SBUs) axially coordinated by a MeIm ligand, which is very beneficial to the electron transfer between the Co(II) ions and oxygen. Combining the photosensitizers ZnTCPP and the electroactive [Co2(-CO2)4] SBUs, the 2D MOF 1 possesses an excellent ECL performance, and can be used as a novel ECL probe for rapid nonamplified detection of the RdRp gene of SARS-CoV-2 with an extremely low limit of detection (≈30 aM).

Enhanced Stability and Function of Probiotic Streptococcus thermophilus with Self-Encapsulation by Increasing the Biosynthesis of Hyaluronan.

The harsh conditions of the gastrointestinal tract limit the potential health benefits of oral probiotics. It is promising that oral bioavailability is improved by strengthening the self-protection of probiotics. Here, we report the encapsulation of a probiotic strain by endogenous production of hyaluronan to enhance the effects of oral administration of the strain. The traditional probiotic Streptococcus thermophilus was engineered to produce hyaluronan shells by using traceless genetic modifications and clustered regularly interspaced short palindromic repeat interference. After oral delivery to mice in the form of fermented milk, hyaluronan-coated S. thermophilus (204.45 mg/L hyaluronan in the milk) exhibited greater survival and longer colonization time in the gut than the wild-type strain. In particular, the engineered probiotic strain could also produce hyaluronan after intestinal colonization. Importantly, S. thermophilus self-encapsulated with hyaluronan increased the number of goblet cells, mucus production, and abundance of the microorganisms related to the biosynthesis of short-chain fatty acids, resulting in the enhancement of the intestinal barrier. The coating formed by endogenous hyaluronan provides an ideal reference for the effective oral administration of probiotics.

Study of the Thermoelectric Properties of Bi2Te3/Sb2Te3 Core-Shell Heterojunction Nanostructures.

Thermoelectric materials convert heat energy into electricity, hold promising capabilities for energy waste harvesting, and may be the future of sustainable energy utilization. In this work, we successfully synthesized core-shell Bi2Te3/Sb2Te3 (BTST) nanostructured heterojunctions via a two-step solution route. Samples with different Bi2Te3 core to Sb2Te3 shell ratios could be synthesized by controlling the reaction precursors. Scanning electron microscopy images show well-defined hexagonal nanoplates and the distinct interfaces between Bi2Te3 and Sb2Te3. The similarity of the area ratios with the precursor ratios indicates that the growth of the Sb2Te3 shell mostly took place on the lateral direction rather than the vertical. Transmission electron microscopy revealed the crystalline nature of the as-synthesized Bi2Te3 core and Sb2Te3 shell. Energy-dispersive X-ray spectroscopy verified the lateral growth of a Sb2Te3 shell on the Bi2Te3 core. Thermoelectric properties were measured on pellets obtained from powders via spark plasma sintering with two different directions, in-plane and out-of-plane, showing anisotropic properties due to the nanostructure alignment in the pellets. All samples showed a degenerate semiconducting character with the electrical resistivity increasing with the temperature. Starting from Sb2Te3, the electrical resistivity increases with the increase in amounts of Bi2Te3. Thermal conductivity is lowered due to the increase in interfaces and additional phonon scattering. We show that the out-of-plane direction of the BTST 1-3 sample (where 1-3 indicates the ratio of BT to ST) demonstrates a high Seebeck value of 145 µV/K at 500 K which may be attributed to an energy filtering effect across the heterojunction interfaces. The highest overall zT is observed for the BTST 1-3 sample in the out-of-plane direction at 500 K. The zT values increase continuously over the measured temperature range, indicating a probable higher value at increased temperatures.

Identification and Characterization of Two Bibenzyl Glycosyltransferases from the Liverwort Marchantia polymorpha.

Liverworts are rich in bibenzyls and related O-glycosides, which show antioxidant activity. However, glycosyltransferases that catalyze the glycosylation of bibenzyls have not yet been characterized. Here, we identified two bibenzyl UDP-glucosyltransferases named MpUGT737B1 and MpUGT741A1 from the model liverwort Marchantia polymorpha. The in vitro enzymatic assay revealed that MpUGT741A1 specifically accepted the bibenzyl lunularin as substrate. MpUGT737B1 could accept bibenzyls, dihydrochalcone and phenylpropanoids as substrates, and could convert phloretin to phloretin-4-O-glucoside and phloridzin, which showed inhibitory activity against tyrosinase and antioxidant activity. The results of sugar donor selectivity showed that MpUGT737B1 and MpUGT741A1 could only accept UDP-glucose as a substrate. The expression levels of these MpUGTs were considerably increased after UV irradiation, which generally caused oxidative damage. This result indicates that MpUGT737B1 and MpUGT741A1 may play a role in plant stress adaption. Subcellular localization indicates that MpUGT737B1 and MpUGT741A1 were expressed in the cytoplasm and nucleus. These enzymes should provide candidate genes for the synthesis of bioactive bibenzyl O-glucosides and the improvement of plant antioxidant capacity.

Single-Crystalline Germanium Nanocrystals via a Two-Step Microwave-Assisted Colloidal Synthesis from GeI4.

Colloidal germanium (Ge) nanocrystals (NCs) are of great interest with possible applications for photovoltaics and near-IR detectors. In many examples of colloidal reactions, Ge(II) precursors are employed, and NCs of diameter ∼3-10 nm have been prepared. Herein, we employed a two-step microwave-assisted reduction of GeI4 in oleylamine (OAm) to prepare monodispersed Ge NCs with a size of 18.9 ± 1.84 nm. More importantly, the as-synthesized Ge NCs showed high crystallinity with single-crystal nature as indicated by powder X-ray diffraction, selected area electron diffraction, and high-resolution transmission electron microscopy. The Tauc plot derived from photothermal deflection spectroscopy measurement on Ge NCs thin films shows a decreased bandgap of the Ge NCs obtained from GeI4 compared with that of the Ge NCs from GeI2 with a similar particle size, indicating a higher crystallinity of the samples prepared with the two-step reaction from GeI4. The calculated Urbach energy indicates less disorder in the larger NCs. This disorder might correlate with the fraction of surface states associated with decreased particle size or with the increased molar ratio of ligands to germanium. Solutions involved in this two-step reaction were investigated with 1H NMR spectroscopy and high-resolution mass spectrometry (MS). One possible reaction pathway is proposed to unveil the details of the reaction involving GeI4 and OAm. Overall, this two-step synthesis produces high-quality Ge NCs and provides new insight on nanoparticle synthesis of covalently bonding semiconductors.

Sequencing Analysis of MiRNA in the Exosomes from Normal and Oxygen and Glucose Deprivation Reperfusion Astrocytes / 中国生物化学与分子生物学报

In this study, high-throughput sequencing technology was used to analyze the differentiallyexpressed microRNA (miRNA) of astrocyte-derived exosomes in control group and oxygen and glucosedeprivation/ reoxygenation (OGD/ R) group. Ultracentrifugation was used to extract exosomes from thesupernatant of astrocyte medium in the control group and OGD/ R group. Transmission electron microscopyshowed that exosomes had a typical vesicle shape with intact membrane and low electron content density. Nanoparticle tracking technology (NTA) detected astrocyte exosomes with a size of 100. 5 ± 31. 1 nm, accounting for 96. 8%. Western blot detection showed that the exosome contained exosome-specificproteins tumor-susceptibility protein (TSG101), heat shock protein 60 (Hsp60), ALG-2-interactingprotein X (ALIX). Compared with the control group, 41 miRNAs in the exosomes of the OGD / R groupwere significantly changed, of which 20 miRNAs were increased and 21 miRNAs were decreasedsignificantly (P < 0. 05). Gene ontology function (GO) analysis showed that significantly differentiallytarget genes were mainly involved in protein glycosylation, lipid metabolism, phosphorylation, Golgiapparatus, endoplasmic reticulum, endosome, cytoplasmic vesicles and cell protrusions, etc. KyotoEncyclopedia of Genes and Genomes (KEGG) pathway analysis found that differential miRNAs weremainly related to metabolic pathways and signaling pathways such as butyrate metabolism, ß-alaninemetabolism, fatty acid degradation, mitophagy and P53 signaling pathway. Sequencing analysis of theexosomal miRNAs derived from control and OGD / R astrocytes and target gene function enrichmentanalysis can be useful for the mechanism study of astrocyte exosomes in response to oxygen and glucosedeprivation reperfusion.

Recent developments in germanium containing clusters in intermetallics and nanocrystals.

Multimetallic clusters can be described as building blocks in intermetallics, compounds prepared from all metals and/or semi-metals, and in Zintl phases, a subset of intermetallics containing metals with large differences in electronegativity. In many cases, these intermetallic and Zintl phases provide the first clue for the possibilities of bond formation between metals and semi-metals. Recent advances in multimetallic clusters found in Zintl phases and nanoparticles focusing on Ge with transition metals and semi-metals is presented. Colloidal routes to Ge nanocrystals provide an opportunity for kinetically stabilized Ge-metal and Ge-semi-metal bonding. These routes provide crystalline nanoclusters of Ge, hereafter referred to as nanocrystals, that can be structurally characterized. Compositions of Ge nanocrystals containing transition metals, and the semi-metals, Sb, Bi, and Sn, whose structures have recently been elucidated through EXAFS, will be presented along with potential applications.