Design, Manufacture, and Characterization of a Critical-Sized Gradient Porosity Dual-Material Tibial Defect Scaffold.

This study proposed a composite tibia defect scaffold with radial gradient porosity, utilizing finite element analysis to assess stress in the tibial region with significant critical-sized defects. Simulations for scaffolds with different porosities were conducted, designing an optimal tibia defect scaffold with radial gradient porosity for repairing and replacing critical bone defects. Radial gradient porosity scaffolds resulted in a more uniform stress distribution, reducing titanium alloy stiffness and alleviating stress shielding effects. The scaffold was manufactured using selective laser melting (SLM) technology with stress relief annealing to simplify porous structure fabrication. The study used New Zealand white rabbits' tibia defect sites as simulation parameters, reconstructing the 3D model and implanting the composite scaffold. Finite element analysis in ANSYS-Workbench simulated forces under high-activity conditions, analyzing stress distribution and strain. In the simulation, the titanium alloy scaffold bore a maximum stress of 122.8626 MPa, while the centrally encapsulated HAp material delivered 27.92 MPa. The design demonstrated superior structural strength, thereby reducing stress concentration. The scaffold was manufactured using SLM, and the uniform design method was used to determine a collection of optimum annealing parameters. Nanoindentation and compression tests were used to determine the influence of annealing on the elastic modulus, hardness, and strain energy of the scaffold.

Development of hybrid 3D printing approach for fabrication of high-strength hydroxyapatite bioscaffold using FDM and DLP techniques.

This study develops a hybrid 3D printing approach that combines fused deposition modeling (FDM) and digital light processing (DLP) techniques for fabricating bioscaffolds, enabling rapid mass production. The FDM technique fabricates outer molds, while DLP prints struts for creating penetrating channels. By combining these components, hydroxyapatite (HA) bioscaffolds with different channel sizes (600, 800, and 1000µm) and designed porosities (10%, 12.5%, and 15%) are fabricated using the slurry casting method with centrifugal vacuum defoaming for significant densification. This innovative method produces high-strength bioscaffolds with an overall porosity of 32%-37%, featuring tightly bound HA grains and a layered surface structure, resulting in remarkable cell viability and adhesion, along with minimal degradation rates and superior calcium phosphate deposition. The HA scaffolds show hardness ranging from 1.43 to 1.87 GPa, with increasing compressive strength as the designed porosity and channel size decrease. Compared to human cancellous bone at a similar porosity range of 30%-40%, exhibiting compressive strengths of 13-70 MPa and moduli of 0.8-8 GPa, the HA scaffolds demonstrate robust strengths ranging from 40 to 73 MPa, paired with lower moduli of 0.7-1.23 GPa. These attributes make them well-suited for cancellous bone repair, effectively mitigating issues like stress shielding and bone atrophy.

High-resolution anatomical and spatial transcriptome analyses reveal two types of meristematic cell pools within the secondary vascular tissue of poplar stem.

The secondary vascular tissue emanating from meristems is central to understanding how vascular plants such as forest trees evolve, grow, and regulate secondary radial growth. However, the overall molecular characterization of meristem origins and developmental trajectories from primary to secondary vascular tissues in woody tree stems is technically challenging. In this study, we combined high-resolution anatomic analysis with a spatial transcriptome (ST) technique to define features of meristematic cells in a developmental gradient from primary to secondary vascular tissues in poplar stems. The tissue-specific gene expression of meristems and derived vascular tissue types were accordingly mapped to specific anatomical domains. Pseudotime analyses were used to track the origins and changes of meristems throughout the development from primary to secondary vascular tissues. Surprisingly, two types of meristematic-like cell pools within secondary vascular tissues were inferred based on high-resolution microscopy combined with ST, and the results were confirmed by in situ hybridization of, transgenic trees, and single-cell sequencing. The rectangle shape procambium-like (PCL) cells develop from procambium meristematic cells and are located within the phloem domain to produce phloem cells, whereas fusiform shape cambium zone (CZ) meristematic cells develop from fusiform metacambium meristematic cells and are located inside the CZ to produce xylem cells. The gene expression atlas and transcriptional networks spanning the primary transition to secondary vascular tissues generated in this work provide new resources for studying the regulation of meristem activities and the evolution of vascular plants. A web server (https://pgx.zju.edu.cn/stRNAPal/) was also established to facilitate the use of ST RNA-seq data.

TSNAdb v2.0: The Updated Version of Tumor-specific Neoantigen Database.

In recent years, neoantigens have been recognized as ideal targets for tumor immunotherapy. With the development of neoantigen-based tumor immunotherapy, comprehensive neoantigen databases are urgently needed to meet the growing demand for clinical studies. We have built the tumor-specific neoantigen database (TSNAdb) previously, which has attracted much attention. In this study, we provide TSNAdb v2.0, an updated version of the TSNAdb. TSNAdb v2.0 offers several new features, including (1) adopting more stringent criteria for neoantigen identification, (2) providing predicted neoantigens derived from three types of somatic mutations, and (3) collecting experimentally validated neoantigens and dividing them according to the experimental level. TSNAdb v2.0 is freely available at https://pgx.zju.edu.cn/tsnadb/.

Integrative analysis reveals a clinicogenomic landscape associated with liver metastasis and poor prognosis in hepatoid adenocarcinoma of the stomach.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) that histologically resembles hepatocellular carcinoma (HCC). Despite its low incidence, HAS had a poor 5-year survival rate. Currently, the linkages between clinicopathological and genomic features of HAS and its therapeutic targets remain largely unknown. Herein, we enrolled 90 HAS patients and 270 stage-matched non-HAS patients from our institution for comparing clinicopathological features. We found that HAS had worse overall survival and were more prone to develop liver metastasis than non-HAS in our cohort, which was validated via meta-analysis. By comparing whole-exome sequencing data of HAS (n=30), non-HAS (n=63), and HCC (n=355, The Cancer Genome Atlas), we identified a genomic landscape associated with unfavorable clinical features in HAS, which contained frequent somatic mutations and widespread copy number variations. Notably, signaling pathways regulating pluripotency of stem cells affected by frequent genomic alterations might contribute to liver metastasis and poor prognosis in HAS patients. Furthermore, HAS developed abundant multiclonal architecture associated with liver metastasis. Encouragingly, target analysis suggested that HAS patients might potentially benefit from anti-ERBB2 or anti-PD-1 therapy. Taken together, this study systematically demonstrated a high risk of liver metastasis and poor prognosis in HAS, provided a clinicogenomic landscape underlying these unfavorable clinical features, and identified potential therapeutic targets, laying the foundations for developing precise diagnosis and therapy in this rare but lethal disease.

Development of Novel Residual-Dense-Attention (RDA) U-Net Network Architecture for Hepatocellular Carcinoma Segmentation.

The research was based on the image recognition technology of artificial intelligence, which is expected to assist physicians in making correct decisions through deep learning. The liver dataset used in this study was derived from the open source website (LiTS) and the data provided by the Kaohsiung Chang Gung Memorial Hospital. CT images were used for organ recognition and lesion segmentation; the proposed Residual-Dense-Attention (RDA) U-Net can achieve high accuracy without the use of contrast. In this study, U-Net neural network was used to combine ResBlock in ResNet with Dense Block in DenseNet in the coder part, allowing the training to maintain the parameters while reducing the overall recognition computation time. The decoder was equipped with Attention Gates to suppress the irrelevant areas of the image while focusing on the significant features. The RDA model was used to identify and segment liver organs and lesions from CT images of the abdominal cavity, and excellent segmentation was achieved for the liver located on the left side, right side, near the heart, and near the lower abdomen with other organs. Better recognition was also achieved for large, small, and single and multiple lesions. The study was able to reduce the overall computation time by about 28% compared to other convolutions, and the accuracy of liver and lesion segmentation reached 96% and 94.8%, with IoU values of 89.5% and 87%, and AVGDIST of 0.28 and 0.80, respectively.

Development of Flexible Biceps Tremors Sensing Chip of PVDF Fibers with Nano-Silver Particles by Near-Field Electrospinning.

Polyvinylidene fluoride (PVDF) and AgNO3/PVDF composite piezoelectric fibers were prepared using near-field electrospinning technology. The prepared fibers are attached to the electrode sheet and encapsulated with polydimethylsiloxane to create an energy acquisition device and further fabricated into a dynamic sensing element. The addition of AgNO3 significantly increased the conductivity of the solution from 40.33 µS/cm to 883.59 µS/cm, which in turn made the fiber drawing condition smoother with the increase of high voltage electric field and reduced the fiber wire diameter size from 0.37 µm to 0.23 µm. The tapping test shows that the voltage signal can reach ~0.9 V at a frequency of 7 Hz, and the energy conversion efficiency is twice that of the PVDF output voltage. The addition of AgNO3 effectively enhances the molecular bonding ability, which effectively increases the piezoelectric constants of PVDF piezoelectric fibers. When the human body is exercised for a long period of time and the body is overloaded, the biceps muscle is found to produce 8 to 16 tremors/second through five arm flexion movements. The voltage output of the flexible dynamic soft sensor is between 0.7-0.9 V and shows an orderly alternating current waveform of voltage signals. The sensor can be used to detect muscle tremors after high-intensity training and to obtain advance information about changes in the symptoms of fasciculation, allowing for more accurate diagnosis and treatment.

A New Design of Porosity Gradient Ti-6Al-4V Encapsulated Hydroxyapatite Dual Materials Composite Scaffold for Bone Defects.

The tibia of New Zealand White rabbits was used as a model of critical bone defects to investigate a new design of composite scaffold for bone defects composed of dual materials. The all-in-one design of a titanium alloy (Ti-6Al-4V) scaffold comprised the structure of a bone plate and gradient porosity cage. Hydroxyapatite (HAp), a biodegradable material, was encapsulated in the center of the scaffold. The gradient pore structure was designed with 70%-65%-60%-55%-50% porosity, since the stresses could be distributed more uniformly when the all-in-one scaffold was placed on the bone contact surface. By covering the center of the scaffold with a low strength of HAp to contact the relatively low strength of bone marrow tissues, the excessive stiffness of the Ti-6Al-4V can be effectively reduced and further diminish the incidence of the stress shielding effect. The simulation results show that the optimized composite scaffold for the 3D model of tibia had a maximum stress value of 27.862 MPa and a maximum strain of 0.065%. The scaffold prepared by selective laser melting was annealed and found that the Young's coefficient increased from 126.44 GPa to 131.46 GPa, the hardness increased from 3.9 GPa to 4.12 GPa, and the strain decreased from 2.27% to 1.13%. The result demonstrates that the removal of residual stress can lead to a more stable structural strength, which can be used as a reference for the design of future clinical tibial defect repair scaffolds.

Recognition Rate Advancement and Data Error Improvement of Pathology Cutting with H-DenseUNet for Hepatocellular Carcinoma Image.

Due to the fact that previous studies have rarely investigated the recognition rate discrepancy and pathology data error when applied to different databases, the purpose of this study is to investigate the improvement of recognition rate via deep learning-based liver lesion segmentation with the incorporation of hospital data. The recognition model used in this study is H-DenseUNet, which is applied to the segmentation of the liver and lesions, and a mixture of 2D/3D Hybrid-DenseUNet is used to reduce the recognition time and system memory requirements. Differences in recognition results were determined by comparing the training files of the standard LiTS competition data set with the training set after mixing in an additional 30 patients. The average error value of 9.6% was obtained by comparing the data discrepancy between the actual pathology data and the pathology data after the analysis of the identified images imported from Kaohsiung Chang Gung Memorial Hospital. The average error rate of the recognition output after mixing the LiTS database with hospital data for training was 1%. In the recognition part, the Dice coefficient was 0.52 after training 50 epochs using the standard LiTS database, while the Dice coefficient was increased to 0.61 after adding 30 hospital data to the training. After importing 3D Slice and ITK-Snap software, a 3D image of the lesion and liver segmentation can be developed. It is hoped that this method could be used to stimulate more research in addition to the general public standard database in the future, as well as to study the applicability of hospital data and improve the generality of the database.

TSNAD v2.0: A one-stop software solution for tumor-specific neoantigen detection.

TSNAD is a one-stop software solution for predicting neoantigens from the whole genome/exome sequencing data of tumor-normal pairs. Here we present TSNAD v2.0 which provides several new features such as the function of RNA-Seq analysis including gene expression and gene fusion analysis, the support of different versions of the reference genome. Most importantly, we replace the NetMHCpan with DeepHLApan we developed previously, which considers both the binding between peptide and major histocompatibility complex (MHC) and the immunogenicity of the presented peptide-MHC complex (pMHC). TSNAD v2.0 achieves good performamce on a standard dataset. For better usage, we provide the Docker version and the web service of TSNAD v2.0. The source code of TSNAD v2.0 is freely available at https://github.com/jiujiezz/tsnad. And the web service of TSNAD v2.0 is available at http://biopharm.zju.edu.cn/tsnad/.

Competitive Real-Time Near Infrared (NIR) Vein Finder Imaging Device to Improve Peripheral Subcutaneous Vein Selection in Venipuncture for Clinical Laboratory Testing.

In this study, near-infrared (NIR) technology was utilized to develop a low-cost real-time near infrared (NIR) guiding device for cannulation. A portable device that can be used by medical practitioners and also by students for their skills development training in performing cannulation. METHODS: First, is the development of a reflectance type optical vein finder using three (3) light emitting diode (LED) lights with 960 nm wavelength, complementary metal-oxide-semiconductor-infrared (CMOS-IR) sensor camera with 1920 × 1080 UXGA (1080P), IR filter set for the given wavelength, and an open-source image processing software. Second, is the actual in-vitro human testing in two sites: the arm and dorsal hand of 242 subjects. The following parameters were included, such as gender, age, mass index (BMI), and skin tone. In order to maximize the assessment process towards the device, the researchers included the arm circumference. This augmented subcutaneous vein imaging study using the develop vein finder device compared the difference in the captured vein images through visual and digital imaging approaches. The human testing was performed in accordance with the ethical standards of the Trinity University of Asia-Institutional Ethics Review Committee (TUA-IERC). RESULTS: The NIR imaging system of the developed vein finder in this study showed its capability as an efficient guiding device through real-time vein pattern recognition, for both sites. Improved captured vein images were observed, having 100% visibility of vein patterns on the dorsal hand site. Fourteen (5.79%) out of 242 subjects reported non-visible peripheral subcutaneous veins in the arm sites. CONCLUSIONS: The developed vein finder device with the NIR technology and reflected light principle with low-energy consumption was efficient for real-time peripheral subcutaneous vein imaging without the application of a tourniquet. This might be utilized as a guiding device in locating the vein for the purpose of cannulation, at a very low cost as compared to the commercially available vein finders. Moreover, it may be used as an instructional device for student training in performing cannulation.

Impact of morphology and collagen-functionalization on the redox equilibria of nanoceria for cancer therapies.

The application of nanoparticulate therapies for cancer depends largely on the uptake and redox activity of the particles. The present work reports the fabrication of different morphologies of nanoceria (CeO2-x) as nanooctahedra (NO), nanorods (NR), and nanocubes (NC) by hydrothermal synthesis at different temperatures (100 °C, 180 °C) of solutions of 0.05 M Ce(NO3)3·6H2O and different concentrations of NaOH (0.01 M, 6.00 M). The characteristics of these nanomorphologies are compared in terms of the crystallinity (XRD), grain size (TEM), surface area (BET), tendency to agglomerate, and the oxygen vacancy concentration ([VO••]) as reflected by the [Ce3+]/[Ce4+] ratio (XPS). The effects of these parameters on the potential cellular uptake are canvassed, suggesting that the nonpolarity of the {111} planes of NO and NR facilitate the preferential uptake of these nanomorphologies. These experimental variables then were normalized through the use of NC as a model substrate for the functionalization using gum arabic (GA) and collagen in order to assess their roles in enhancing redox activity. Both the unfunctionalized and functionalized NC were noncytotoxic in in vitro tests with Kuramochi ovarian cancer cells. However, the antioxidant behavior of the collagen-functionalized NC was superior to that of the unfunctionalized NC, which was superior to that of the controls. These results demonstrate that, while the intrinsic VO•• of CeO2-x enhance the destruction of reactive oxygen species (ROS), functionalization by gum arabic and collagen crosslinking as extrinsic additions to the system enhances ROS destruction to an even greater extent. The antioxidant behavior and potential to neutralize superoxide and hydroxyl radicals of these materials offers new potential for the improvement of nanoparticulate cancer therapies.

Polaron-formation revealed by transient XUV imaginary refractive index changes in different iron compounds.

We use transient extreme ultraviolet (XUV) reflection absorption spectroscopy to study polaron formation on hematite and akaganeite surfaces. We observed a reduction in the offset of the imaginary refractive index (κoffset) that was attributed to the photoemission cross-section. The difference in the κoffset reduction indicated that deeper-trapped polarons were formed in hematite than in akaganeite.

Effect of Kangquan Recipe () on BAMBI Expression in Hypothalamic-Pituitary-Prostate in Rats with Benign Prostatic Hyperplasia.

OBJECTIVE: To investigate the effect of Kangquan Recipe (, KQR) on bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) expression and its mechanism in rats with benign prostatic hyperplasia (BPH). METHODS: Forty-eight male Sprague-Dawley rats were divided into 6 groups using a random number table, with 8 in each group: the normal group (normal saline 10 mL/kg), the model group (normal saline 10 mL/kg), the finasteride group (0.5 mg/kg), the low-dose KQR group (3.5 g/kg), the middle-dose KQR group (7 g/kg), and the high-dose KQR group (14 g/kg). The 40 rats were subcutaneously injected with testosterone propionate after castration for 30 days to establish the BPH rat model except for those in the normal group. At the same time, the corresponding drugs were administered by gavage for 30 consecutive days. The effects of different doses of KQR on the protate wet weight, prostate volume and prostate index (PI) were observed. The changes in histopathology were monitored with hematoxylin-eosin staining. BAMBI protein and mRNA expression contents were determined by Western blot and quantitative real-time polymerase chain reaction, respectively. RESULTS: All doses of KQR could decrease prostatic epithelial tissue proliferation. Compared to the model group, the high and middle-dose KQR significantly reduced prostate wet weight, prostate volume and PI; increased BAMBI protein expression in the hypothalamus, pituitary and prostate tissue; all doses of KQR up-regulated BAMBI mRNA expression in serum, prostatic fluid and prostate tissue (P<0.05 or P<0.01). CONCLUSIONS: KQR could inhibit the proliferation of rat prostatic tissue, promote BAMBI protein expression in the hypothalamic-pituitary-prostate of rats with BPH; and increase BAMBI mRNA expression in the blood, prostatic fluid and prostate tissue of rats with BPH, showing a dose-effect relationship. KQR can be used as a potential drug for the treatment of BPH.

In-Series U-Net Network to 3D Tumor Image Reconstruction for Liver Hepatocellular Carcinoma Recognition.

Cancer is one of the common diseases. Quantitative biomarkers extracted from standard-of-care computed tomography (CT) scan can create a robust clinical decision tool for the diagnosis of hepatocellular carcinoma (HCC). According to the current clinical methods, the situation usually accounts for high expenditure of time and resources. To improve the current clinical diagnosis and therapeutic procedure, this paper proposes a deep learning-based approach, called Successive Encoder-Decoder (SED), to assist in the automatic interpretation of liver lesion/tumor segmentation through CT images. The SED framework consists of two different encoder-decoder networks connected in series. The first network aims to remove unwanted voxels and organs and to extract liver locations from CT images. The second network uses the results of the first network to further segment the lesions. For practical purpose, the predicted lesions on individual CTs were extracted and reconstructed on 3D images. The experiments conducted on 4300 CT images and LiTS dataset demonstrate that the liver segmentation and the tumor prediction achieved 0.92 and 0.75 in Dice score, respectively, by as-proposed SED method.

Enhancement of PVDF Sensing Characteristics by Retooling the Near-Field Direct-Write Electrospinning System.

This research aimed to develop a direct-write near-field electrospinning system (DW-NFES) with three-axis positioning of controllable speed, torque and position to produce sizable and high-quality piezoelectric fibers for sensing purposes. Sensor devices with high electrical response signals were developed and tested. To achieve DW-NFES purpose, a servo motor controller was designed to develop a high response rate, accurate positioning, and stable mobile device through the calculation of bandwidth and system time delay. With this retooled system of DW-NFES, controllable and uniform size fibers in terms of diameters, stretching force, and interspaces can be obtained. Sensor devices can be made selectively without a complicated lithography process. The characteristics of this DW-NFES platform were featured by high response rate, accurate positioning, and stable movement to make fibers with high piezoelectric property. In this study, polyvinylidene fluoride (PVDF) was used to explore and enhance their sensing quality through the platform. The parametric study of the process factors on piezoelectric sensing signals mainly included the concentration of electrospinning PVDF solution, high voltage electric field, and collection speed. Finally, the surface morphology and piezoelectric properties of the as-electrospun PVDF fibers were examined by scanning electron microscopy (SEM) and characterized by electrical response measurement techniques. The results showed that the fiber spinning speed of the DW-NFES system could be increased to ~125 from ~20 mm/s and the accuracy precision was improved to ~1 from ~50 µm, compared to conventional step motor system. The fiber diameter reached ~10 µm, and the electrospinning pitch reached to as small as ~10 µm. The piezoelectric output voltage of the electrospun fibers was increased ~28.6% from ~97.2 to ~125 mV; the current was increased ~27.6% from ~163 to ~208 nA, suggesting that the piezoelectric signals can be enhanced significantly by using this retooled system. Finally, an external control module (Arduino-MAGE) was introduced to control the PVDF piezoelectric fiber sensors integrated as a sensing array. The behavior of long-term sedentary patients can be successfully detected by this module system to prevent the patients from the bedsores.

Spatially dependent H-bond dynamics at interfaces of water/biomimetic self-assembled lattice materials.

Understanding hydrogen-bond interactions in self-assembled lattice materials is crucial for preparing such materials, but the role of hydrogen bonds (H bonds) remains unclear. To gain insight into H-bond interactions at the materials' intrinsic spatial scale, we investigated ultrafast H-bond dynamics between water and biomimetic self-assembled lattice materials (composed of sodium dodecyl sulfate and ß-cyclodextrin) in a spatially resolved manner. To accomplish this, we developed an infrared pump, vibrational sum-frequency generation (VSFG) probe hyperspectral microscope. With this hyperspectral imaging method, we were able to observe that the primary and secondary OH groups of ß-cyclodextrin exhibit markedly different dynamics, suggesting distinct H-bond environments, despite being separated by only a few angstroms. We also observed another ultrafast dynamic reflecting a weakening and restoring of H bonds between bound water and the secondary OH of ß-cyclodextrin, which exhibited spatial uniformity within self-assembled domains, but heterogeneity between domains. The restoration dynamics further suggest heterogeneous hydration among the self-assembly domains. The ultrafast nature and meso- and microscopic ordering of H-bond dynamics could contribute to the flexibility and crystallinity of the material--two critically important factors for crystalline lattice self-assemblies--shedding light on engineering intermolecular interactions for self-assembled lattice materials.

Nanoscale optical pulse limiter enabled by refractory metallic quantum wells.

The past several decades have witnessed rapid development of high-intensity, ultrashort pulse lasers, enabling deeper laboratory investigation of nonlinear optics, plasma physics, and quantum science and technology than previously possible. Naturally, with their increasing use, the risk of accidental damage to optical detection systems rises commensurately. Thus, various optical limiting mechanisms and devices have been proposed. However, restricted by the weak optical nonlinearity of natural materials, state-of-the-art optical limiters rely on bulk liquid or solid media, operating in the transmission mode. Device miniaturization becomes complicated with these designs while maintaining superior integrability and controllability. Here, we demonstrate a reflection-mode pulse limiter (sub-100 nm) using nanoscale refractory films made of Al2O3/TiN/Al2O3 metallic quantum wells (MQWs), which provide large and ultrafast Kerr-type optical nonlinearities due to the quantum size effect of the MQW. Functional multilayers consisting of these MQWs could find important applications in nanophotonics, nonlinear optics, and meta-optics.

Band gap engineering of Ce-doped anatase TiO2 through solid solubility mechanisms and new defect equilibria formalism.

The present work reports a detailed mechanistic interpretation of the role of the solubility of dopants and resultant midgap defect energies in band gap engineering. While there is a general perception that a single dopant is associated with single solubility and defect mechanisms, in reality, the potential for multiple solubility and defect mechanisms requires a more nuanced interpretation. Similarly, Kröger-Vink defect equilibria assume that stoichiometries during substitutional and interstitial solid solubility as well as Schottky and Frenkel pair formation are compensated by the diffusion of matrix ions to the grain boundaries or surface. However, this approach does not allow the possibility that stoichiometry is uncompensated, where diffusion of the matrix ion to lattice interstices occurs, followed by charge compensation by redox of this ion. Consequently, a modified defect equilibria formalism has been developed in order to allow description of this situation. Experimental data for the structural, chemical, semiconducting, and photocatalytic properties as a function of doping level are correlated with conceptual structural models, a comprehensive energy band diagram, and the corresponding defect equilibria. These correlations reveal the complex mechanisms of the interrelated solubility and defect formation mechanisms, which change significantly and irregularly as a function of small changes in doping level. The analyses confirm that the assumption of single mechanisms of solid solubility and defect formation may be simplifications of more complex processes. The generation of (1) a matrix of complementary characterisation and analytical data, (2) the calculation of a complete energy band diagram, (3) consideration of charge compensation mechanisms and redox beyond the limitations of Kröger-Vink approaches, and (4) the development of models of corresponding structural analogies combine to create a new approach to interpret and explain experimental data. These strategies allow deconstruction of these complex issues and thus targeting of optimal and possibly unique doping levels to achieve lattice configurations that may be energetically and structurally unfavorable. These approaches then can be applied to other doped semiconducting systems.