An innovative exploration to identify and isolate the dominant-flocculated-species from polytitanium chloride synthesized by electrodialysis.

Abundance of dominant-flocculated-species is the key to determine coagulation performance of coagulant. Titanium-based coagulants have garnered considerable attention due to their high coagulation efficiency, but with a current challenge of the identification and isolation of the dominant-flocculated-species. Herein, polytitanium chloride (PTC), enriched with dominant-flocculated-species, was successfully synthesized by electrodialysis through accurate micro-interface control of the reaction among Ti-hydrolyzed-species and OH-. Special attention was paid to a feasible and high-effective strategy to isolate the dominant-flocculated-species from PTC through one-step rapid ultrafiltration. Selective preference was the ultrafiltration membranes (made of polyethersulfone) with a molecular weight cut-off of 5 kDa, which enabled the isolation of the dominant-flocculated-species, named PTC-5k. Results from the electrospray time-of-flight mass spectrometry (ESI-TOF-MS) proved a large proportion of the small and medium-sized hydrolyzed products as dominant-flocculated-species in PTC-5k, with the main signals concentrated between m/z 100 and 500. This composition achieved approximately 15.0% higher removal of organic matter with a 33.0% reduction in dosage compared to PTC. Unique snowflake-like branched structure of PTC-5k enhanced the coagulation mechanisms of sweeping and adsorption-bridging flocculation. Worth noting was the more compact flocs formed by PTC-5k than PTC, which was the probable reason for the mitigated fouling of ceramic membrane when PTC-5k was utilized as pre-treatment methodology. Continuous operation of ceramic membrane filtration up to 30 h, demonstrated 30% improvement in stable flux compared to PTC. This study provides the strategy for the isolation of Ti-dominant-flocculated-species, and lays the foundation for practical application.

Continuous planting of euhalophyte Suaeda salsa enhances microbial diversity and multifunctionality of saline soil.

Halophyte-based remediation emerges as a novel strategy for ameliorating saline soils, offering a sustainable alternative to conventional leaching methods. While bioremediation is recognized for its ability to energize soil fertility and structure, the complex interplays among plant traits, soil functions, and soil microbial diversity remain greatly unknown. Here, we conducted a 5-year field experiment involving the continuous cultivation of the annual halophyte Suaeda salsa in saline soils to explore soil microbial diversity and their relationships with plant traits and soil functions. Our findings demonstrate that a decline in soil salinity corresponded with increases in the biomass and seed yield of S. salsa, which sustained a consistent seed oil content of approximately 22% across various salinity levels. Significantly, prolonged cultivation of halophytes substantially augmented soil microbial diversity, particularly from the third year of cultivation. Moreover, we identified positive associations between soil multifunctionality, seed yield, and taxonomic richness within a pivotal microbial network module. Soils enriched with taxa from this module showed enhanced multifunctionality and greater seed yields, correlating with the presence of functional genes implicated in nitrogen fixation and nitrification. Genomic analysis suggests that these taxa have elevated gene copy numbers of crucial functional genes related to nutrient cycling. Overall, our study emphasizes that the continuous cultivation of S. salsa enhances soil microbial diversity and recovers soil multifunctionality, expanding the understanding of plant-soil-microbe feedback in bioremediation.IMPORTANCEThe restoration of saline soils utilizing euhalophytes offers a viable alternative to conventional irrigation techniques for salt abatement and soil quality enhancement. The ongoing cultivation of the annual Suaeda salsa and its associated plant traits, soil microbial diversity, and functionalities are, however, largely underexplored. Our investigation sheds light on these dynamics, revealing that cultivation of S. salsa sustains robust plant productivity while fostering soil microbial diversity and multifunctionality. Notably, the links between enhanced soil multifunctionality, increased seed yield, and network-dependent taxa were found, emphasizing the importance of key microbial taxa linked with functional genes vital to nitrogen fixation and nitrification. These findings introduce a novel understanding of the role of soil microbes in bioremediation and advance our knowledge of the ecological processes that are vital for the rehabilitation of saline environments.

Co-fermentation of titanium-flocculated-sludge with food waste towards simultaneous water purification and resource recovery.

Recovery of resources from domestic sewage and food waste has always been an international-thorny problem. Titanium-based flocculation can achieve high-efficient destabilization, quick concentration and separation of organic matter from sewage to sludge. This study proposed co-fermentation of the titanium-flocculated sludge (Ti-loaded sludge) and food waste towards resource recovery by converting organic matter to value-added volatile fatty acids (VFAs) and inorganic matter to struvite and TiO2 nanoparticles. When Ti-loaded sludge and food waste were co-fermented at a mass ratio of 3:1, the VFAs yield reached 3725.2 mg-COD/L (VFAs/SCOD 91.0%), which was more than 4 times higher than the case of the sludge alone. The 48-day semicontinuous co-fermentation demonstrated stable long-term operation, yielding VFAs at 2529.0 mg-COD/L (VFAs/SCOD 89.8%) and achieving a high CODVFAs/NNH4 of 58.9. Food waste provided sufficient organic substrate, enriching plenty of acid-producing fermentation bacteria (such as Prevotella 7 about 21.0% and Bacteroides about 9.4%). Moreover, metagenomic sequencing analysis evidenced the significant increase of the relative gene abundance corresponding to enzymes in pathways, such as extracellular hydrolysis, substrates metabolism, and VFAs biosynthesis. After fermentation, the precious element P (≥ 99.0%) and extra-added element Ti (≥99.0%) retained in fermented residues, without releasing to VFAs supernatant, which facilitated the direct re-use of VFAs as resource. Through simple and commonly used calcination and acid leaching methodologies, 80.9% of element P and 82.1% of element Ti could be successfully recovered as struvite and TiO2 nanoparticles, respectively. This research provides a strategy for the co-utilization of domestic sludge and food waste, which can realize both reduction of sludge and recovery of resources.

Dynamic Transformation of Nano-MoS2 in a Soil-Plant System Empowers Its Multifunctionality on Soybean Growth.

Molybdenum disulfide (nano-MoS2) nanomaterials have shown great potential for biomedical and catalytic applications due to their unique enzyme-mimicking properties. However, their potential agricultural applications have been largely unexplored. A key factor prior to the application of nano-MoS2 in agriculture is understanding its behavior in a complex soil-plant system, particularly in terms of its transformation. Here, we investigate the distribution and transformation of two types of nano-MoS2 (MoS2 nanoparticles and MoS2 nanosheets) in a soil-soybean system through a combination of synchrotron radiation-based X-ray absorption near-edge spectroscopy (XANES) and single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS). We found that MoS2 nanoparticles (NPs) transform dynamically in soil and plant tissues, releasing molybdenum (Mo) and sulfur (S) that can be incorporated gradually into the key enzymes involved in nitrogen metabolism and the antioxidant system, while the rest remain intact and act as nanozymes. Notably, there is 247.9 mg/kg of organic Mo in the nodule, while there is only 49.9 mg/kg of MoS2 NPs. This study demonstrates that it is the transformation that leads to the multifunctionality of MoS2, which can improve the biological nitrogen fixation (BNF) and growth. Therefore, MoS2 NPs enable a 30% increase in yield compared to the traditional molybdenum fertilizer (Na2MoO4). Excessive transformation of MoS2 nanosheets (NS) leads to the overaccumulation of Mo and sulfate in the plant, which damages the nodule function and yield. The study highlights the importance of understanding the transformation of nanomaterials for agricultural applications in future studies.

Spiral Large-Dimension Microfluidic Channel for Flow-Rate- and Particle-Size-Insensitive Focusing by the Stabilization and Acceleration of Secondary Flow.

Inertial microfluidics has demonstrated its ability to focus particles in a passive and straightforward manner. However, achieving flow-rate- and particle-size-insensitive focusing in large-dimension channels with a simple design remains challenging. In this study, we developed a spiral microfluidic with a large-dimension channel to achieve inertial focusing. By designing a unique "big buffering area" and a "small buffering area" in the spiral microchannel, we observed the stabilization and acceleration of secondary flow. Our optimized design allowed for efficient (>99.9%) focusing of 15 µm particles within a wide range of flow rates (0.5-4.5 mL/min) during a long operation duration (0-60 min). Additionally, we achieved effective (>95%) focusing of different-sized particles (7, 10, 15, and 30 µm) and three types of tumor cells (K562, HeLa, and MCF-7) near the inner wall of the 1 mm wide outlet when applying different flow rates (1-3 mL/min). Finally, successful 3D cell focusing was achieved within an optimized device, with the cells positioned at a distance of 50 µm from the wall. Our strategy of stabilizing and accelerating Dean-like secondary flow through the unique configuration of a "big buffering area" and a "small buffering area" proved to be highly effective in achieving inertial focusing that is insensitive to the flow rate and particle size, particularly in large-dimension channels. Consequently, it shows great potential for use in hand-operated microfluidic tools for flow cytometry.

CircLARP1B promotes pyroptosis of high glucose-induced renal mesangial cells by regulating the miR-578/TLR4 axis.

BACKGROUND: Diabetic nephropathy (DN) is a main cause of end-stage renal disease with high mortality. Circular RNAs (circRNAs) are associated with the pathogenesis of DN. This study aimed to explore the role of circLARP1B in DN. METHODS: The levels of circLARP1B, miR-578, TLR4 in DN and high glucose (HG)-treated cells using quantitative real-time PCR. Their relationship was analyzed using dual-luciferase reporter assay. The biological behaviors were assessed by MTT assay, EDU assay, flow cytometry, ELISA, and western blot. RESULTS: The results indicated that circLARP1B and TLR4 were highly expressed, and miR-578 was low expressed in patients with DN and HG-induced cells. Knockdown of circLARP1B promoted the proliferation and cell cycle, and inhibited pyroptosis and inflammation of HG-induced cells. CircLARP1B is a sponge of miR-578, which targets TLR4. Rescue experiments showed that inhibition of miR-578 reversed the effects of circLARP1B knockdown, while TLR4 reversed the effects of miR-578. CONCLUSION: CircLARP1B/miR-578/TLR4 axis suppressed the proliferation, blocked cell cycle at the G0-G1 phase, promoted pyroptosis, and inflammatory factor release of renal mesangial cells induced by HG. The findings suggested that circLARP1B may be a target for the treatment of DN.

Effects of nitrogen supply on hydrogen-oxidizing bacterial enrichment to produce microbial protein: Comparing nitrogen fixation and ammonium assimilation.

To investigate the effects of nitrogen source supply on microbial protein (MP) production by hydrogen-oxidizing bacteria (HOB) under continuous feed gas provision, a sequencing batch culture comparison (N2 fixation versus ammonium assimilation) was performed. The results confirmed that even under basic cultivation conditions, N2-fixing HOB (NF-HOB) communities showed higher levels of CO2 and N2 fixation (190.45 mg/L Δ CODt and 11.75 mg/L Δ TNbiomass) than previously known, with the highest biomass yield being 0.153 g CDW/g COD-H2. Rich ammonium stimulated MP synthesis and the biomass accumulation of communities (increased by 7.4 ～ 14.3 times), presumably through the enhancement of H2 and CO2 absorption. The micro mechanism may involve encouraging the enrichment of species like Xanthobacter and Acinetobacter then raising the abundance of nitrogenase and glutamate synthase to facilitate the nitrogen assimilation. This would provide NF-HOB with ideas for optimizing their MP synthesis activity.

Deep learning models for preoperative T-stage assessment in rectal cancer using MRI: exploring the impact of rectal filling.

Background: The objective of this study was twofold: firstly, to develop a convolutional neural network (CNN) for automatic segmentation of rectal cancer (RC) lesions, and secondly, to construct classification models to differentiate between different T-stages of RC. Additionally, it was attempted to investigate the potential benefits of rectal filling in improving the performance of deep learning (DL) models. Methods: A retrospective study was conducted, including 317 consecutive patients with RC who underwent MRI scans. The datasets were randomly divided into a training set (n = 265) and a test set (n = 52). Initially, an automatic segmentation model based on T2-weighted imaging (T2WI) was constructed using nn-UNet. The performance of the model was evaluated using the dice similarity coefficient (DSC), the 95th percentile Hausdorff distance (HD95), and the average surface distance (ASD). Subsequently, three types of DL-models were constructed: Model 1 trained on the total training dataset, Model 2 trained on the rectal-filling dataset, and Model 3 trained on the non-filling dataset. The diagnostic values were evaluated and compared using receiver operating characteristic (ROC) curve analysis, confusion matrix, net reclassification index (NRI), and decision curve analysis (DCA). Results: The automatic segmentation showed excellent performance. The rectal-filling dataset exhibited superior results in terms of DSC and ASD (p = 0.006 and 0.017). The DL-models demonstrated significantly superior classification performance to the subjective evaluation in predicting T-stages for all test datasets (all p < 0.05). Among the models, Model 1 showcased the highest overall performance, with an area under the curve (AUC) of 0.958 and an accuracy of 0.962 in the filling test dataset. Conclusion: This study highlighted the utility of DL-based automatic segmentation and classification models for preoperative T-stage assessment of RC on T2WI, particularly in the rectal-filling dataset. Compared with subjective evaluation, the models exhibited superior performance, suggesting their noticeable potential for enhancing clinical diagnosis and treatment practices.

High-Throughput Blood Plasma Extraction in a Dimension-Confined Double-Spiral Channel.

Microfluidic technologies enabling the control of secondary flow are essential for the successful separation of blood cells, a process that is beneficial for a wide range of medical research and clinical diagnostics. Herein, we introduce a dimension-confined microfluidic device featuring a double-spiral channel designed to regulate secondary flows, thereby enabling high-throughput isolation of blood for plasma extraction. By integrating a sequence of micro-obstacles within the double-spiral microchannels, the stable and enhanced Dean-like secondary flow across each loop can be generated. This setup consequently prompts particles of varying diameters (3, 7, 10, and 15 µm) to form different focusing states. Crucially, this system is capable of effectively separating blood cells of different sizes with a cell throughput of (2.63-3.36) × 108 cells/min. The concentration of blood cells in outlet 2 increased 3-fold, from 1.46 × 108 to 4.37 × 108, while the number of cells, including platelets, exported from outlets 1 and 3 decreased by a factor of 608. The engineering approach manipulating secondary flow for plasma extraction points to simplicity in fabrication, ease of operation, insensitivity to cell size, high throughput, and separation efficiency, which has potential utility in propelling the development of miniaturized diagnostic devices in the field of biomedical science.

Flow-Rate-Insensitive Plasma Extraction by the Stabilization and Acceleration of Secondary Flow in the Ultralow Aspect Ratio Spiral Channel.

Although microfluidic devices have made remarkable strides in blood cell separation, there is still a need for further development and improvement in this area. Herein, we present a novel ultralow aspect ratio (H/W = 1:36) spiral channel microfluidic device with ordered micro-obstacles for sheathless and flow-rate-insensitive blood cell separation. By introducing ordered micro-obstacles into the spiral microchannels, reduced magnitude fluctuations in secondary flow across different loops can be obtained through geometric confinement. As a result, the unique Dean-like secondary flow can effectively enhance the separation efficiency of particles in different sizes ranging from 3 to 15 µm. Compared to most existing microfluidic devices, our system offers several advantages of easy manufacturing, convenient operation, long-term stability, highly efficient performance (up to 99.70% rejection efficiency, including platelets), and most importantly, insensitivity to cell sizes as well as flow rates (allowing for efficient separation of different-sized blood cells in a wide flow rate from 1.00 to 2.50 mL/min). The unique characteristics, such as ultralow aspect ratio, sequential micro-obstacles, and controlled secondary flow, make our device a promising solution for practical plasma extraction in biomedical research and clinical applications.

Utilization of halophytes in saline agriculture and restoration of contaminated salinized soils from genes to ecosystem: Suaeda salsa as an example.

Halophytes can be used to screen genes for breeding salt-tolerant crops and are of great value in the restoration of salinized or contaminated soils. However, the potential of halophytes in improving saline soils remains limited. In this paper, based on the latest research progress, we use Suaeda salsa L. as an example to evaluate the value of halophytes in developing saline agriculture including: 1) some defined salt-resistance genes and high-affinity nitrate transporter genes in the species for breeding salt-tolerance and nitrogen efficiency crops; 2) the value of S. salsa and microorganisms from S. salsa in remediation of heavy metal contaminated and organic polluted saline soils; and 3) the capacity to remove salts from soils and the application of the species. In conclusion, S. salsa has high value as a candidate to explore the theoretical base and practical application for utilizing halophytes to improve salinized soils from genes to ecosystem.

Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells.

Ecto-5'-nucleotidase (CD73), encoded by the NT5E gene, mediates tumor immunosuppression and has been targeted for the development of new anticancer drugs. Proteasome inhibitors impair protein degradation by inhibiting proteasome and have been used in the clinic for cancer therapy. Here we report that proteasome inhibitors reduce the protein and mRNA levels of CD73. Among 127 tested small-molecule drugs, proteasome inhibitors were found to consistently decrease the protein and mRNA levels of CD73 in NSCLC NCI-H1299 cells. This effect was further confirmed in different NSCLC cells exposed to different proteasome inhibitors. In those treated cells, the protein levels of ERK and its active form p-ERK, the vital components in the MAPK pathway, were reduced. Consistently, inhibitors of MEK and ERK, another two members of the MAPK pathway, also lowered the protein and mRNA levels of CD73. Correspondingly, treatments with fibroblast growth factor 2 (FGF2), an activator of the MAPK pathway, enhanced the levels of p-ERK and partly rescued the proteasome inhibitor-driven reduction of CD73 mRNA and protein in NSCLC cells. However, exogenous CD73 overexpression in murine Lewis lung carcinoma (LLC) cells was not lowered either in vitro or in vivo, by the treatments with proteasome inhibitors and basically, did not affect their in vitro proliferative inhibition either. In contrast, CD73 overexpression dramatically reduced the in vivo anticancer activity of Bortezomib in immunocompetent mice, with tumor growth inhibition rates from 52.18 % for LLC/vector down to 8.75 % for LLC/NT5E homografts. These findings give new insights into the anticancer mechanisms of proteasome inhibitors.

Pollen Morphology in Sorbus L. (Rosaceae) and Its Taxonomic Implications.

The genus Sorbus L. in the Rosaceae family is taxonomically challenging due to its morphological variation, polyploidy, and interspecific hybridization. In this study, we used scanning electron microscopy (SEM) to observe the pollen morphology of eighty species, representing six subgenera, in order to assess the differences within the genus Sorbus and its pollen characteristics. We conducted a cluster analysis on three qualitative and four quantitative characteristics. The results demonstrated that the pollen grains of the studied Sorbus species are isopolar and tricolporate. We identified five types of pollen shapes: suboblate, spheroidal, subprolate, prolate, and perprolate. The pollen ornamentation of the investigated species could be classified into five types: striate-perforate, striate, cerebroid-perforate, cerebroid, and foveolate. Interestingly, within the same subgenera, different species exhibited multiple types of characters. The cluster analysis indicated that all 80 species could be divided into six groups, with group B consisting exclusively of species from the subgenus Sorbus. Although pollen micro-morphologies alone do not provide sufficient evidence to establish the taxonomic relationships of the subgenera within Sorbus, they do offer valuable information for species-level taxonomic treatment.

Molybdenum Nanofertilizer Boosts Biological Nitrogen Fixation and Yield of Soybean through Delaying Nodule Senescence and Nutrition Enhancement.

Soybean (Glycine max) is a crop of global significance and has low reliance on N fertilizers due to its biological nitrogen fixation (BNF) capacity, which harvests ambient N2 as a critical ecosystem service. BNF can be severely compromised by abiotic stresses. Enhancing BNF is increasingly important not only to alleviate global food insecurity but also to reduce the environmental impact of agriculture by decreasing chemical fertilizer inputs. However, this has proven challenging using current genetic modification or bacterial nodulation methods. Here, we demonstrate that a single application of a low dose (10 mg/kg) of molybdenum disulfide nanoparticles (MoS2 NPs) can enhance soybean BNF and grain yield by 30%, compared with conventional molybdate fertilizer. Unlike molybdate, MoS2 NPs can more sustainably release Mo, which then is effectively incorporated as a cofactor for the synthesis of nitrogenase and molybdenum-based enzymes that subsequently enhance BNF. Sulfur is also released sustainably and incorporated into biomolecule synthesis, particularly in thiol-containing antioxidants. The superior antioxidant enzyme activity of MoS2 NPs, together with the thiol compounds, protect the nodules from reactive oxygen species (ROS) damage, delay nodule aging, and maintain the BNF function for a longer term. The multifunctional nature of MoS2 NPs makes them a highly effective strategy to enhance plant tolerance to abiotic stresses. Given that the physicochemical properties of nanomaterials can be readily modulated, material performance (e.g., ROS capturing capacity) can be further enhanced by several synthesis strategies. This study thus demonstrates that nanotechnology can be an efficient and sustainable approach to enhancing BNF and crop yield under abiotic stress and combating global food insecurity.

Systematic and Comprehensive Analysis of tRNA-Derived Small RNAs Reveals Their Potential Regulatory Roles and Clinical Relevance in Sarcoidosis.

Introduction: The pathogenesis of sarcoidosis, which involves several systems, is unclear, and its pathological type is non-caseating epithelioid granulomas. tRNA-derived small RNA (tsRNA) is a novel class of short non-coding RNAs with potential regulatory functions. However, whether tsRNA contributes to sarcoidosis pathogenesis remains unclear. Methods: Deep sequencing technology was used to identify alterations in tsRNA relative abundance profiles between patients with sarcoidosis and healthy controls and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate. The clinical parameters were analysis to evaluate the clinical feature correlations initially. Target prediction and bioinformatics analysis of validated tsRNA were conducted to explore the mechanisms of tsRNAs in sarcoidosis pathogenesis. Results: A total of 360 tsRNAs were identified for exact matches. Among them, the relative abundance of three tRNAs (tiRNA-Glu-TTC-001, tiRNA-Lys-CTT-003, and tRF-Ser-TGA-007) was markedly regulated in sarcoidosis. The levels of various tsRNAs were significantly correlated with age, the number of affected systems, and calcium levels in the blood. Additionally, target prediction and bioinformatics analyses revealed that these tsRNAs may play roles in chemokine, cAMP, cGMP-PKG, retrograde endorphin, and FoxO signalling pathways. The related genes, APP, PRKACB, ARRB2, and NR5A1 finding may participate in the occurrence and development of sarcoidosis through immune inflammation. Conclusion: This study provides novel insights to explore tsRNA as a novel and efficacious pathogenic target of sarcoidosis.

Multi-heteroatom-doping promotes molecular oxygen activation on polymeric carbon nitride for simultaneous generation of H2O2 and degradation of oxcarbazepine.

Simultaneously realizing the efficient generation of H2O2 and degradation of pollutants is of great significance for environmental remediation. However, most polymeric semiconductors only show moderate performance in molecular oxygen (O2) activation due to the sluggish electron-hole pair dissociation and charge transfer dynamics. Herein, we develop a simple thermal shrinkage strategy to construct multi-heteroatom-doped polymeric carbon nitride (K, P, O-CNx). The resultant K, P, O-CNx not only improves the separation efficiency of charge carriers, but also improves the adsorption/activation capacity of O2. K, P, O-CNx significantly increases the production of H2O2 and the degradation activity of oxcarbazepine (OXC) under visible light. K, P, O-CN5 shows a high H2O2 production rate (1858 µM h-1 g-1) in water under visible light, far surpassing that of pure PCN. The apparent rate constant for OXC degradation by K, P, O-CN5 increases to 0.0491 min-1, which is 8.47 times that of PCN. Density functional theory (DFT) calculations show that the adsorption energy of O2 near phosphorus atoms in K, P, O-CNx is the highest. This work provides a new idea for the efficient degradation of pollutants and generation of H2O2 at the same time.

Observation of Confinement-Free Neutral Group Three Transition Metal Carbonyls Sc(CO)7 and TM(CO)8 (TM=Y, La).

Spectroscopic characterization of neutral highly-coordinated compounds is essential in fundamental and applied research, but has been proven to be a challenging experimental target because of the difficulty in mass selection. Here, we report the preparation and size-specific infrared-vacuum ultraviolet (IR-VUV) spectroscopic identification of group-3 transition metal carbonyls Sc(CO)7 and TM(CO)8 (TM=Y, La) in the gas phase, which are the first confinement-free neutral heptacarbonyl and octacarbonyl complexes. The results indicate that Sc(CO)7 has a C2v structure and TM(CO)8 (TM=Y, La) have a D4h structure. Theoretical calculations predict that the formation of Sc(CO)7 and TM(CO)8 (TM=Y, La) is both thermodynamically exothermic and kinetically facile in the gas phase. These highly-coordinated carbonyls are 17-electron complexes when only those valence electrons that occupy metal-CO bonding orbitals are considered, in which the ligand-only 4b1u molecular orbital is ignored. This work opens new avenues toward the design and chemical control of a large variety of compounds with unique structures and properties.

A chromosome-level genome assembly of Hong Kong catfish (Clarias fuscus) uncovers a sex-determining region.

BACKGROUND: Hong Kong catfish (Clarias fuscus) is an ecologically and economically important species that is widely distributed in freshwater regions of southern China. Hong Kong catfish has significant sexual growth dimorphism. The genome assembly of the Hong Kong catfish would facilitate study of the sex determination and evolution mechanism of the species. RESULTS: The first high-quality chromosome-level genome of the Hong Kong catfish was constructed. The total genome was 933.4 Mb, with 416 contigs and a contig N50 length of 8.52 Mb. Using high-throughput chromosome conformation capture (Hi-C) data, the genome assembly was divided into 28 chromosomes with a scaffold N50 length of 36.68 Mb. A total of 23,345 protein-coding genes were predicted in the genome, and 94.28% of the genes were functionally annotated in public databases. Phylogenetic analysis indicated that C. fuscus and Clarias magur diverged approximately 63.7 million years ago. The comparative genome results showed that a total of 60 unique, 353 expanded and 851 contracted gene families were identified in Hong Kong catfish. A sex-linked quantitative trait locus identified in a previous study was located in a sex-determining region of 30.26 Mb (0.02 to 30.28 Mb) on chromosome 13 (Chr13), the predicted Y chromosome. This QTL region contained 785 genes, of which 18 were identified as sex-related genes. CONCLUSIONS: This study is the first to report the chromosome-level genome assembly of Hong Kong catfish. The study provides an excellent genetic resource that will facilitate future studies of sex determination mechanisms and evolution in fish.

Formulation and Scale-Up of Fast-Dissolving Lumefantrine Nanoparticles for Oral Malaria Therapy.

Lumefantrine (LMN) is one of the first-line drugs in the treatment of malaria due to its long circulation half-life, which results in enhanced effectiveness against drug-resistant strains of malaria. However, LMN's therapeutic efficacy is diminished due to its low bioavailability when dosed as a crystalline solid. The goal of this work was to produce low-cost, highly bioavailable, stable LMN powders for oral delivery that would be suitable for global health applications. We report the development of a LMN nanoparticle formulation and the translation of that formulation from laboratory to industrial scale. We applied Flash NanoPrecipitation (FNP) to develop nanoparticles with 90% LMN loading and sizes of 200-260 nm. The integrated process involves nanoparticle formation, concentration by tangential flow ultrafiltration, and then spray drying to obtain a dry powder. The final powders are readily redispersible and stable over accelerated aging conditions (50°C, 75% RH, open vial) for at least 4 weeks and give equivalent and fast drug release kinetics in both simulated fed and fasted state intestinal fluids, making them suitable for pediatric administration. The nanoparticle-based formulations increase the bioavailability of LMN 4.8-fold in vivo when compared to the control crystalline LMN. We describe the translation of the laboratory-scale process at Princeton University to the clinical manufacturing scale at WuXi AppTec.