Dendrite initiation and propagation in lithium metal solid-state batteries.

All-solid-state batteries with a Li anode and ceramic electrolyte have the potential to deliver a step change in performance compared with today's Li-ion batteries1,2. However, Li dendrites (filaments) form on charging at practical rates and penetrate the ceramic electrolyte, leading to short circuit and cell failure3,4. Previous models of dendrite penetration have generally focused on a single process for dendrite initiation and propagation, with Li driving the crack at its tip5-9. Here we show that initiation and propagation are separate processes. Initiation arises from Li deposition into subsurface pores, by means of microcracks that connect the pores to the surface. Once filled, further charging builds pressure in the pores owing to the slow extrusion of Li (viscoplastic flow) back to the surface, leading to cracking. By contrast, dendrite propagation occurs by wedge opening, with Li driving the dry crack from the rear, not the tip. Whereas initiation is determined by the local (microscopic) fracture strength at the grain boundaries, the pore size, pore population density and current density, propagation depends on the (macroscopic) fracture toughness of the ceramic, the length of the Li dendrite (filament) that partially occupies the dry crack, current density, stack pressure and the charge capacity accessed during each cycle. Lower stack pressures suppress propagation, markedly extending the number of cycles before short circuit in cells in which dendrites have initiated.

THItoGene: a deep learning method for predicting spatial transcriptomics from histological images.

Spatial transcriptomics unveils the complex dynamics of cell regulation and transcriptomes, but it is typically cost-prohibitive. Predicting spatial gene expression from histological images via artificial intelligence offers a more affordable option, yet existing methods fall short in extracting deep-level information from pathological images. In this paper, we present THItoGene, a hybrid neural network that utilizes dynamic convolutional and capsule networks to adaptively sense potential molecular signals in histological images for exploring the relationship between high-resolution pathology image phenotypes and regulation of gene expression. A comprehensive benchmark evaluation using datasets from human breast cancer and cutaneous squamous cell carcinoma has demonstrated the superior performance of THItoGene in spatial gene expression prediction. Moreover, THItoGene has demonstrated its capacity to decipher both the spatial context and enrichment signals within specific tissue regions. THItoGene can be freely accessed at https://github.com/yrjia1015/THItoGene.

Development and Validation of a Predictive Model for Resistance to Platinum-Based Chemotherapy in Patients with Ovarian Cancer through Proteomic Analysis.

Platinum resistance in ovarian cancer poses a significant challenge, substantially impacting patient outcomes. Developing an accurate predictive model is crucial for improving clinical decision-making and guiding treatment strategies. Proteomic data from 217 high-grade serous ovarian cancer (HGSOC) biospecimens obtained from JHU, PNNL, and PTRC were used to construct a prediction model for identifying individuals who are resistant to platinum-based chemotherapy. A total of 6437 common proteins were detected across all data sets, with 26 proteins overlapping between the development cohorts JHU and PNNL. Using LASSO and logistic regression analysis, a six-protein model (P31323_PRKAR2B, Q13309_SKP2, Q14997_PSME4, Q6ZRP7_QSOX2, Q7LGA3_HS2ST1, and Q7Z2Z2_EFL1) was developed, which accurately predicted platinum resistance, with an AUC of 0.964 (95% CI, 0.929-0.999). Internal validation by resampling resulted in a C-index of 0.972 (95% CI 0.894-0.988). External validation performed on the PTRC cohort achieved an AUC of 0.855 (95% CI 0.748-0.963). Calibration curves showed good consistency, and DCA indicated superior clinical utility. The model also performed well in predicting PFS and OS at various time points. Based on these proteins, our predictive model can precisely predict platinum response and survival outcomes in HGSOC patients, which can assist clinicians in promptly identifying potentially platinum-resistant individuals.

Developing Rapid-Charging Li-S Batteries via "Target Catalysis" of Cations and Anions Modified Electrocatalyst.

The shuttle effect and sluggish sulfur reduction reaction have resulted in significantly low efficiency and poor high current cycling stability in lithium-sulfur batteries, impeding their practical applications. To address these challenges, the introduction of Ni cations into MoS2 grown on reduced graphene oxide (MoS2/rGO) induces the formation of impurity energy levels between the conduction and valence bands of MoS2. Additionally, the introduction of anionic Se expands the interlayer spacing, enhances intrinsic conductivity, and improves ion diffusion rates. Simultaneously introducing anionic and cationic species into the MoS2/rGO causes the center of the d-band to shift upward, reducing the occupancy of electrons in antibonding orbitals. This modification leads to a rearrangement of the electronic structure of Mo, accelerating the redox reactions of lithium polysulfides. It particularly enhances the binding energy and lowers the conversion energy barrier of Li2S4. Consequently, the Li||S coin cell with the Ni-MoSSe/rGO cathode demonstrates an initial capacity of 446 mAh g-1 at 20 C, with a remarkable capacity retention of ≈96.7% after 200 cycles. Moreover, even under high sulfur loading conditions (6.45 mg cm-2) and a low electrolyte/sulfur ratio (5.4 µL mg-2), it maintains a high areal capacity of 6.42 mAh cm-2.

Epigenetic regulation of HBV-specific tumor-infiltrating T cells in HBV-related HCC.

BACKGROUND AND AIMS: HBV shapes the T-cell immune responses in HBV-related HCC. T cells can be recruited to the nidus, but limited T cells participate specifically in response to the HBV-related tumor microenvironment and HBV antigens. How epigenomic programs regulate T-cell compartments in virus-specific immune processes is unclear. APPROACH AND RESULTS: We developed Ti-ATAC-seq. 2 to map the T-cell receptor repertoire, epigenomic, and transcriptomic landscape of αß T cells at both the bulk-cell and single-cell levels in 54 patients with HCC. We deeply investigated HBV-specific T cells and HBV-related T-cell subsets that specifically responded to HBV antigens and the HBV + tumor microenvironment, respectively, characterizing their T-cell receptor clonality and specificity and performing epigenomic profiling. A shared program comprising NFKB1/2-, Proto-Oncogene, NF-KB Sub unit, NFATC2-, and NR4A1-associated unique T-cell receptor-downstream core epigenomic and transcriptomic regulome commonly regulated the differentiation of HBV-specific regulatory T-cell (Treg) cells and CD8 + exhausted T cells; this program was also selectively enriched in the HBV-related Treg-CTLA4 and CD8-exhausted T cell-thymocyte selection associated high mobility subsets and drove greater clonal expansion in HBV-related Treg-CTLA4 subset. Overall, 54% of the effector and memory HBV-specific T cells are governed by transcription factor motifs of activator protein 1, NFE2, and BACH1/2, which have been reported to be associated with prolonged patient relapse-free survival. Moreover, HBV-related tumor-infiltrating Tregs correlated with both increased viral titer and poor prognosis in patients. CONCLUSIONS: This study provides insight into the cellular and molecular basis of the epigenomic programs that regulate the differentiation and generation of HBV-related T cells from viral infection and HBV + HCC unique immune exhaustion.

High-precision high-stability acousto-optic pulse picking driver with a direct digital synthesis technique.

A method for maintaining a fixed phase relationship between the driving signal of acousto-optic modulator (AOM) and the original mode-locked seed laser is proposed and realized, which stabilizes the amplitude of diffracted signal output from the AOM for subsequent amplification. A field-programmable gate array (FPGA), combined with external summing amplifiers, is used to directly synthesize high-timing-precision driving signals that are synchronized with the seed laser pulses, and the accuracy of signal timing control reaches 160 ps. Using this driver, the standard deviation of the diffracted signal output from the AOM is significantly decreased from 0.52% to 0.18%. This pulse-picking solution also includes a control system that can flexibly control the frequency, gating width, etc., of the driving signal, which makes it more convenient for subsequent laser amplification and makes it suitable for a variety of mode-locked lasers.

Phase Transition Control in Molecular Solids via Complementarity of Hydrogen-Bond Strength.

Phase transitions in molecular solids involve synergistic changes in chemical and electronic structures, leading to diversification in physical and chemical properties. Despite the pivotal role of hydrogen bonds (H-bonds) in many phase-transition materials, it is rare and challenging to chemically regulate the dynamics and to elucidate the structure-property relationship. Here, four high-spin CoII compounds were isolated and systematically investigated by modifying the ligand terminal groups (X=S, Se) and substituents (Y=Cl, Br). S-Cl and Se-Br undergo a reversible structural phase transition near room temperature, triggering the rotation of 15-crown-5 guests and the swing between syn- and anti-conformation of NCX- ligands, accompanied by switchable magnetism. Conversely, S-Br and Se-Cl retain stability in ordered and disordered phases, respectively. H-bonds geometric analysis and ab initio calculations reveal that the electronegativity of X and Y affects the strength of NY-ap-H⋅⋅⋅X interactions. Entropy-driven structural phase transitions occur when the H-bond strength is appropriate; otherwise, the phase stays unchanged if it is too strong or weak. This work highlights a phase transition driven by H-bond strength complementarity - pairing strong acceptor with weak donor and vice versa, which offers a straightforward and effective approach for designing phase-transition molecular solids from a chemical perspective.

Spin-State Control in Dysprosium(III) Metallacrown Magnets via Thioacetal Modification.

Integrating controllable spin states into single-molecule magnets (SMMs) enables precise manipulation of magnetic interactions at a molecular level, but remains a synthetic challenge. Herein, we developed a 3d-4f metallacrown (MC) magnet [DyNi5(quinha)5(Clsal)2(py)8](ClO4) ⋅ 4H2O (H2quinha=quinaldichydroxamic acid, HClsal=5-chlorosalicylaldehyde) wherein a square planar NiII is stabilized by chemical stacking. Thioacetal modification was employed via post-synthetic ligand substitutions and yielded [DyNi5(quinha)5(Clsaldt)2(py)8](ClO4) ⋅ 3H2O (HClsaldt=4-chloro-2-(1,3-dithiolan-2-yl)phenol). Thanks to the additional ligations of thioacetal onto the NiII site, coordination-induced spin state switching (CISSS) took place with spin state altering from low-spin S=0 to high-spin S=1. The synergy of CISSS effect and magnetic interactions results in distinct energy splitting and magnetic dynamics. Magnetic studies indicate prominent enhancement of reversal barrier from 57 cm-1 to 423 cm-1, along with hysteresis opening and an over 200-fold increment in coercive field at 2 K. Ab initio calculations provide deeper insights into the exchange models and rationalize the relaxation/tunnelling pathways. These results demonstrate here provide a fire-new perspective in modulating the magnetization relaxation via the incorporation of controllable spin states and magnetic interactions facilitated by the CISSS approach.

Divergent response to abiotic factor determines the decoupling of water and carbon fluxes over an artificial C4 shrub in desert.

Knowledge on relationship and determinants of water and carbon dioxide (CO2) exchange is crucial to land managers and policy makers especially for the desertified land restoration. However, there remains highly uncertain in terms of water use and carbon sequestration for artificial plantation in desert. Here, continuous water and carbon fluxes were measured using eddy covariance (EC) in conjunction with hydrometeorological measurements over an artificial C4 shrub, Haloxylon ammodendron (C. A. Mey.) Bunge, from July 2020 to 2021 in Tengger Desert, China. Throughout 2021, evapotranspiration (ET) was 189.5 mm, of which 85% (150 mm) occurred during growing season, that was comparable with the summation of precipitation (132.2 mm), dew (33.5 mm) and potential other sources (e.g. deep subsoil water). This ecosystem was a strong carbon sink with net ecosystem production (NEP) up to 446.4 g C m-2 yr-1, much higher than surrounding sites. Gross primary production (GPP, 598.7 g C m-2 yr-1) in this shrubland was comparable with that of other shrublands, whereas ecosystem respiration (Re, 152.3 g C m-2 yr-1) was lower. Random Forest showed that environmental factors can explain 71.56% and 80.07% variation of GPP and ET, respectively. Interestingly, environmental factors have divergent effect on water and carbon exchange, i.e., soil hydrothermic factors (soil moisture content and soil temperature) determine the magnitude and seasonal pattern of ET and Re, while aerodynamics factors (net radiation, atmospheric temperature and wind speed) determine GPP and NEP. As such, divergent response of abiotic factors resulted in the decoupling of water and carbon exchange. Our results suggest that H. ammodendron is a suitable species for large-scale afforestation in dryland given its low water use but high carbon sequestration. Therefore, we infer that artificial planting H. ammodendron in dryland could provide an opportunity for climate change mitigation, and the long-term time series data is needed to confirm its sustainable role of carbon sequestration in the future.

Chronological and Carbohydrate-Dependent Transformation of Fatty Acids in the Larvae of Black Soldier Fly Following Food Waste Treatment.

Although black soldier fly larvae (BSFL) can convert food waste into insectile fatty acids (FAs), the chronological and diet-dependent transformation of larval FAs has yet to be determined. This study focused on the dynamics of larval FA profiles following food waste treatment and characterized factors that may drive FA composition and bioaccumulation. Larval FA matters peaked on Day 11 as 7.7 ± 0.7% of food waste dry matter, maintained stably from Day 11-19, and decreased slightly from Day 19-21. The BSFL primarily utilized waste carbohydrates for FA bioconversion (Day 0-11) and shifted to waste FAs (Day 7-17) when the carbohydrates were close to depletion. The optimal time window for larvae harvest was Days 17-19, which fulfilled both targets of waste oil removal and larval FA transformation. Larval FAs were dominated by C12:0, followed by C18:2, C18:1, and C16:0. The waste-reducing carbohydrate primarily accounted for larval FA bioaccumulation (r = -0.947, p < 0.001). The increase in diet carbohydrate ratio resulted in the elevation of larval C12:0 yield, which indicated that larval C12:0-FA was primarily biosynthesized from carbohydrates and further transformed from ≥C16 FAs. This study elucidates the bioaccumulation process of larval FAs for food waste treatment and highlights the importance of waste carbohydrates for both the composition and transformation of larval FAs.

Square Root Convexity of Fisher Information along Heat Flow in Dimension Two.

Recently, Ledoux, Nair, and Wang proved that the Fisher information along the heat flow is log-convex in dimension one, that is d2dt2log(I(Xt))≥0 for n=1, where Xt is a random variable with density function satisfying the heat equation. In this paper, we consider the high dimensional case and prove that the Fisher information is square root convex in dimension two, that is d2dt2IX≥0 for n=2. The proof is based on the semidefinite programming approach.

Intratumoral stem-like CCR4+ regulatory T cells orchestrate the immunosuppressive microenvironment in HCC associated with hepatitis B.

BACKGROUND & AIMS: Regulatory T cell (Treg) depletion increases antitumor immunity. However, severe autoimmunity can occur following systemic loss of Tregs, which could be avoided by selectively depleting intratumoral Tregs. Herein, we aimed to investigate the role of tumor-infiltrating CCR4+ Tregs in hepatocellular carcinoma (HCC) and to provide a potential target strategy for immunotherapy. METHODS: CCR4+ Tregs were analyzed by flow cytometry in murine models and clinical samples. The function of tumor-infiltrating and induced CCR4+ Tregs was interrogated by genetic and epigenetic approaches. To block CCR4+ Treg chemotaxis, we developed an N-terminus recombinant protein of CCR4 (N-CCR4-Fc) as a neutralizing pseudo-receptor that effectively bound to its ligand CCL22. The efficacy of CCR4 antagonism as an immunotherapeutic agent was evaluated by tumor weights, growth kinetics and survival curves. RESULTS: CCR4+ Tregs were the predominant type of Tregs recruited to hepatitis B-associated HCC (HBV+ HCC), correlating with sorafenib resistance and HBV load titers. Compared with CCR4- Tregs, CCR4+ Tregs exhibited increased IL-10 and IL-35 expression, and enhanced functionality in suppressing CD8+ T cells. CCR4+ Tregs also displayed PD-1+TCF1+ stem-like properties. ATAC-seq data revealed substantial chromatin remodeling between tumor-infiltrating Tregs (TIL-Tregs) and induced Tregs, suggesting that long-term chromatin reprogramming accounted for the acquisition of enhanced immunosuppressive stem-like specificity by CCR4+ TIL-Tregs. Treatment with a CCR4 antagonist or N-CCR4-Fc blocked intratumoral Treg accumulation, overcame sorafenib resistance, and sensitized tumors to PD-1 checkpoint blockade. CONCLUSIONS: Intratumoral stem-like CCR4+ Tregs orchestrated immunosuppressive resource cells in the tumor microenvironment. CCR4 could be targeted to enhance antitumor immunity by specifically blocking infiltration of Tregs into the tumor microenvironment and inhibiting maintenance of the TIL-Treg pool. LAY SUMMARY: Targeting regulatory T cells is a promising approach in cancer immunotherapy; however, severe autoimmunity can occur following systemic regulatory T cell loss. This could be avoided by selectively depleting intratumoral regulatory T cells. Herein, targeting intratumoral stem-like CCR4+ regulatory T cells helped to overcome sorafenib resistance and sensitize tumors to immune checkpoint blockade in mouse models of liver cancer. This approach could have wide clinical applicability.

Comparison of anther transcriptomes in response to cold stress at the reproductive stage between susceptible and resistant Japonica rice varieties.

BACKGROUND: Rice is one of the most important cereal crops in the world but is susceptible to cold stress (CS). In this study, we carried out parallel transcriptomic analysis at the reproductive stage on the anthers of two Japonica rice varieties with contrasting CS resistance: cold susceptible Longjing11 (LJ11) and cold resistant Longjing25 (LJ25). RESULTS: According to the obtained results, a total of 16,762 differentially expressed genes (DEGs) were identified under CS, including 7,050 and 14,531 DEGs in LJ25 and LJ11, respectively. Examining gene ontology (GO) enrichment identified 35 up- and 39 down-regulated biological process BP GO terms were significantly enriched in the two varieties, with 'response to heat' and 'response to cold' being the most enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified 33 significantly enriched pathways. Only the carbon metabolism and amino acid biosynthesis pathways with down-regulated DEGs were enriched considerably in LJ11, while the plant hormone signal transduction pathway (containing 153 DEGs) was dramatically improved. Eight kinds of plant hormones were detected in the pathway, while auxin, abscisic acid (ABA), salicylic acid (SA), and ethylene (ETH) signaling pathways were found to be the top four pathways with the most DEGs. Furthermore, the protein-protein interaction (PPI) network analysis identified ten hub genes (co-expressed gene number ≥ 30), including six ABA-related genes. Various DEGs (such as OsDREB1A, OsICE1, OsMYB2, OsABF1, OsbZIP23, OsCATC, and so on) revealed distinct expression patterns among rice types when the DEGs between LJ11 and LJ25 were compared, indicating that they are likely responsible for CS resistance of rice in cold region. CONCLUSION: Collectively, our findings provide comprehensive insights into complex molecular mechanisms of CS response and can aid in CS resistant molecular breeding of rice in cold regions.

Adduct-based p-doping of organic semiconductors.

Electronic doping of organic semiconductors is essential for their usage in highly efficient optoelectronic devices. Although molecular and metal complex-based dopants have already enabled significant progress of devices based on organic semiconductors, there remains a need for clean, efficient and low-cost dopants if a widespread transition towards larger-area organic electronic devices is to occur. Here we report dimethyl sulfoxide adducts as p-dopants that fulfil these conditions for a range of organic semiconductors. These adduct-based dopants are compatible with both solution and vapour-phase processing. We explore the doping mechanism and use the knowledge we gain to 'decouple' the dopants from the choice of counterion. We demonstrate that asymmetric p-doping is possible using solution processing routes, and demonstrate its use in metal halide perovskite solar cells, organic thin-film transistors and organic light-emitting diodes, which showcases the versatility of this doping approach.

High-efficiency 940- and 969-nm brightness-maintaining wavelength-multiplexed LD-pumped 240-W thin-rod Yb:YAG amplifier.

A high-efficiency ultrafast laser amplifier based on thin-rod Yb:YAG was demonstrated, featuring a 940- and 969-nm brightness-maintaining wavelength-multiplexed laser diode (LD)-pumping method. Two high-brightness LDs (940 nm and 969 nm) were spectrally combined into one beam spatially with a dichroic mirror, thus enabling twice pump power while maintaining high brightness. A maximum signal power of 240 W was obtained at a repetition rate of 1 MHz, with a power extraction efficiency (PEE) of ∼51%. To the best of the authors' knowledge, this is the first report of >50% efficiency as well as the highest average power operating at the fundamental mode for thin-rod Yb:YAG amplifiers. The beam quality factors (M2) of the amplified signal were measured to be 1.72 and 1.12 for the horizontal and vertical directions, respectively. A preliminary pulse compression was conducted at a signal power of 80 W with a chirped volume Bragg grating (CVBG) compressor. The compressed pulse duration was 744 fs with an average power of 66.5 W, corresponding to a compression efficiency of 83.1%.

Self-Assembly Synthesis of a [2]Catenane CoII Single-Molecule Magnet.

We describe herein the self-assembly synthesis of an octanuclear CoII [2]catenane {[Co4 (H2 L)6 ]2 16+ } formed by the mechanical interlocking of two {[Co4 (H2 L)6 ]8+ } rectangles of unprecedented topology. Subtle manipulation of the synthetic conditions allows the isolation of a mixed-valence [Co2 III /Co2 II ]10+ non-catenated rectangle. The CoII centers in the [2]catenane exhibit slow relaxation of their magnetic moment, i. e. single-molecule magnet properties, dominated by quantum tunneling and Raman relaxation processes. This work shows that metallo-supramolecular chemistry can precisely control the organization of single-molecule magnets in topologically complex arrangements.

Reversible Switchability of Magnetic Anisotropy and Magnetodielectric Effect Induced by Intermolecular Motion.

Introducing magnetic switchability into artificial molecular machines is fascinating for precise control of magnetism via external stimuli. Herein, a field-induced CoII single-molecule magnet was found to exhibit the reversible switch of Jahn-Teller distortion near room temperature, along with thermal conformational motion of the 18-crown-6 rotor, which pulls the coordinated H2 O to rotate through intermolecular hydrogen bonds and triggers a single-crystal-to-single-crystal phase transition with Twarm =282 K and Tcool =276 K. Interestingly, the molecular magnetic anisotropy probed by single-crystal angular-resolved magnetometry revealed the reorientation of easy axis by 14.6°. Moreover, ON/OFF negative magnetodielectric effects were respectively observed in the high-/low-temperature phase, which manifests the spin-lattice interaction in the high-temperature phase could be stronger, in accompanied by the hydrogen bonding between the rotating 18-crown-6 and the coordinated H2 O.

Exploiting the single-photon detection performance of InGaAs negative-feedback avalanche diode with fast active quenching.

InGaAs/InP-based negative-feedback avalanche diodes (NFADs) for 1550 nm single-photon detection with easy-to-use and low-afterpulsing features have attracted many researchers on lidar and quantum optics. Here we present a fast active-quenching circuit specifically designed to exploit the performance of a multi-mode fiber coupled NFAD for free-running operation by a further suppression on afterpulsing effects. The quenching and recovery processes of the device were characterized using electroluminescent method and a novel dual-pulse method, respectively. Results show that the proposed circuit was capable of reducing the time required for quenching and recovery process of the NFAD by approximately 20 ns, and contributed to a reduction in the number of avalanche carriers by up to 30%. As a result, the total afterpulse probability (TAP) of the NFAD with active quenching was reduced by up to 70% compared with the condition without active quenching, and by approximately 90% compared with a standard InGaAs SPAD at the photon detection efficiency (PDE) of 20%. The TAP of the proposed detector was lower than 11% when the dead time was longer than 200 ns, 600 ns, and 2 µs at the PDE of 10%, 15%, and 25%, respectively, and the usable dead time was down to 80 ns with a TAP of 20.4% at the PDE of 10%, 1550 nm, 223 K, where the DCR was as low as 918 Hz. The low-afterpulsing, low-dead-time, low-DCR features of this compact detector makes it especially suitable for use in lidar applications.

Site-specific specimen preparation for SIMS analysis of radioactive samples.

Secondary Ion Mass Spectrometry is an important technique for the study of the composition of a wide range of materials because of the exceptionally high sensitivity that allows the study of trace elements and the ability to distinguish isotopes that can be used as markers for reactions and transport processes. However, when studying nuclear materials, it is often necessary to analyse highly radioactive samples, and only rather few SIMS facilities are available in active environments. In this paper, we present a methodology using focussed ion beam milling to prepare samples from radioactive specimens that are sufficiently large to undertake SIMS mapping experiments over microstructurally significant regions, but with overall activities small enough to be readily transported and analysed by a SIMS instrument in a normal laboratory environment. Radioactive samples prepared using this methodology can also be used for correlative SIMS analysis with other analytical microscopies. SIMS results showing the distributions of deuterium in oxides on in-reactor corroded zirconium alloys are presented to demonstrate the potential of this sample preparation technique.

Real-Time Monitoring of Solid-Liquid Slurries: Optimized Synthesis of Tetrabenazine.

Solid-liquid slurries are vital and increasingly prevalent in the pharmaceutical and chemical industries. Despite the importance of these heterogeneous systems, process control and optimization are fundamentally hindered by a lack of compatible real-time analytical techniques. We present herein an online HPLC monitoring platform enabling access to real-time compositional information on slurries. We demonstrate the system by investigating the heterogeneous synthesis reaction of tetrabenazine. Furthermore, we integrated our online HPLC platform with the orthogonal monitoring techniques of a pH probe and a microscopic imaging probe to provide additional mechanistic insight. These combined insights enable the optimization of tetrabenazine synthesis in terms of reaction time, byproduct formation, and diastereomeric purity of the final product.