Core-shell Ru@Co2P synergistic catalyst as polysulfides adsorption-catalytic conversion mediator with enhanced redox kinetics in lithium-sulfur batteries.

Lithium-sulfur batteries (LSBs) have emerged as the research hotspot due to their compelling merits, including high specific capacity (1675 mAh g-1), theoretical energy density (2600 Wh kg-1), environmental friendliness, and economic advantages. However, challenges still exist for further application due to their inherent issues such as the natural insulation, shuttle effect, and volume expansion of sulfur cathode during the continuous cycle processes. These factors obstruct the lithium ions (Li+) transfer process and sulfur utilization, resulting in significant impedance and inducing inferior battery performance. Herein, the core-shell nanocube anchoring ruthenium atoms and dicobalt phosphate (Ru@Co2P@NC) were fabricated as the effective catalyst and inhibited barrier for LSBs. On the one hand, the core-shell structure offers numerous channels to expedite Li+ diffusion. On the other hand, ruthenium (Ru) and dicobalt phosphate (Co2P) active sites facilitate the chemical capture of lithium polysulfides (LiPSs), accelerating sluggish kinetics. Ru@Co2P@NC modified cells not only exhibited a high initial specific capacity (1609.35 mAh g-1) at 0.5C and enduring stability with high specific capacity retention of 906.60 mAh g-1 at 0.5C after 400 cycles but also possessed low capacity attenuation rate of 0.07 % per cycle after 600 cycles (1C, Sulfur loading: 1.2 mg). Interestingly, the modified cells demonstrated a high specific capacity and long-cycle stability with high sulfur loading (from 1.984 to 3.137 mg), which provides a promising research approach for high-performance LSBs.

A nomogram and heat map based on LASSO-Cox regression for predicting the risk of early-stage severe fever with thrombocytopenia syndrome patients developing into critical illness at 7-day and 14-day.

Severe fever with thrombocytopenia syndrome (SFTS) represents an emerging infectious disease characterized by a substantial mortality risk. Early identification of patients is crucial for effective risk assessment and timely interventions. In the present study, least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was conducted to identify key risk factors associated with progression to critical illness at 7-day and 14-day. A nomogram was constructed and subsequently assessed for its predictive accuracy through evaluation and validation processes. The risk stratification of patients was performed using X-tile software. The performance of this risk stratification system was assessed using the Kaplan-Meier method. Additionally, a heat map was generated to visualize the results of these analyses. A total of 262 SFTS patients were included in this study, and four predictive factors were included in the nomogram, namely viral copies, aspartate aminotransferase (AST) level, C-reactive protein (CRP), and neurological symptoms. The AUCs for 7-day and 14-day were 0.802 [95% confidence interval (CI): 0.707-0.897] and 0.859 (95% CI: 0.794-0.925), respectively. The nomogram demonstrated good discrimination among low, moderate, and high-risk groups. The heat map effectively illustrated the relationships between risk groups and predictive factors, providing valuable insights with high predictive and practical significance.

Dynamic phosphorylation of FOXA1 by Aurora B guides post-mitotic gene reactivation.

FOXA1 serves as a crucial pioneer transcription factor during developmental processes and plays a pivotal role as a mitotic bookmarking factor to perpetuate gene expression profiles and maintain cellular identity. During mitosis, the majority of FOXA1 dissociates from specific DNA binding sites and redistributes to non-specific binding sites; however, the regulatory mechanisms governing molecular dynamics and activity of FOXA1 remain elusive. Here, we show that mitotic kinase Aurora B specifies the different DNA binding modes of FOXA1 and guides FOXA1 biomolecular condensation in mitosis. Mechanistically, Aurora B kinase phosphorylates FOXA1 at Serine 221 (S221) to liberate the specific, but not the non-specific, DNA binding. Interestingly, the phosphorylation of S221 attenuates the FOXA1 condensation that requires specific DNA binding. Importantly, perturbation of the dynamic phosphorylation impairs accurate gene reactivation and cell proliferation, suggesting that reversible mitotic protein phosphorylation emerges as a fundamental mechanism for the spatiotemporal control of mitotic bookmarking.

Construction and validation of a dynamic nomogram using Lasso-logistic regression for predicting the severity of severe fever with thrombocytopenia syndrome patients at admission.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression. METHODS: All eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model's performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance. RESULTS: 299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017-1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003-1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175-2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005-1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035-26.858; P < 0.001) and hemorrhage symptoms (OR, 3.414; 95% CI, 1.096-10.974; P = 0.035). The AUC-ROC, C-index, calibration plots, and DCA demonstrated the robust performance of the nomogram in predicting severity at admission, and Kaplan-Meier survival analysis indicated its utility in predicting 28-day mortality among SFTS patients. The dynamic nomogram is accessible at https://sfts.shinyapps.io/SFTS_severity_nomogram/ . CONCLUSION: This study provided a practical and readily applicable tool for the early identification of high-risk SFTS patients, enabling the timely initiation of intensified treatments and protocol adjustments to mitigate disease progression.

Hydrothermal carbonization of Chinese medicine residue from licorice: Effects of pore and chemical structures on chromium migration.

The Chinese medicine residue (CMR) is composed of wet substances, so using hydrothermal carbonization (HTC) to recover renewable energy from the residue is a suitable treatment method. Chromium (Cr), a kind of heavy metal element, is enriched in hydrochar and severely restricts its effective utilization. An in-depth analysis of the migration path and mechanism of Cr in hydrochar is helpful in promoting energy utilization for CMR. Here, licorice, a significant Chinese medicine, was selected as the example to analyze the evolutions of its pore and chemical structures and their effects on the migration mechanism of Cr during the HTC process. The products obtained under various HTC conditions were analyzed using nitrogen adsorption, FTIR, and 13C NMR. The results show that, considering reaction time and relevant reactions as the primary factors during the HTC process, the migration pathway of Cr in hydrochar undergoes two stages, and they are the accompanying migration stage and the recovery aggregation stage. Active adsorption sites for Cr may exist within the pore structure of hydrochar. In the HTC process, hydrolysis, decarboxylation, and decarbonylation reactions are the direct drivers of Cr migration, while aromatization is the underlying cause of Cr recovery and aggregation. It is hypothesized that Cr catalyzes the acetylene cyclotrimerization reaction, thereby promoting the formation of aromatic structures in hydrochar and integrating into the hydrochar carbon skeleton.

Liver Extracellular Vesicles and Particles Enriched ß-Sitosterol Effectively Promote Liver Regeneration in Mice.

Background: The liver's regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver's interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear. Methods: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed ß-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of ß-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a ß-sitosterol diet on liver regeneration was verified in mice. Results: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70-130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified ß-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased ß-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls. Conclusion: Liver-derived EVPs promote regeneration after partial hepatectomy. ß-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway.

Differences in HDL-related coronary heart disease risk between individuals with and without diabetes.

BACKGROUND AND AIMS: High-density lipoprotein (HDL) might lose atheroprotective functions in the presence of diabetes. We sought to examine associations of HDL cholesterol (HDL-C) and HDL particle (HDL-P) subclasses with risk of coronary heart disease (CHD) stratified by diabetes. METHODS: We included 393,516 participants (20,691 diabetics and 372,825 nondiabetics) from the UK Biobank. Restricted cubic splines cooperated with Cox model were used to estimate associations of HDL with CHD. RESULTS: During a median follow-up of 13.0 years, 3398 (16.4 %) and 24,772 (6.6 %) incident CHD events occurred among diabetics and nondiabetics, respectively. HDL-C showed inverse associations with CHD among nondiabetics, whereas U-shaped associations among diabetics. Compared to individuals with normal HDL-C (40th - 60th percentile, 1.32-1.51 mmol/L), those in the top percentile (95th, >2.16 mmol/L) had lower CHD risks among nondiabetics (Hazard Ratio, 0.79; 95 % confidence interval, 0.73-0.86), but higher risks among diabetics (1.38, 1.02-1.88). As for HDL-P, there were inverted U-shaped associations of very large HDL-P and linearly negative associations of large HDL-P with CHD among nondiabetics; however, linearly positive associations of very large HDL-P and null associations of large HDL were observed among diabetics. L-shaped associations of medium and small HDL-P were found both in diabetics and nondiabetics. CONCLUSIONS: Very high HDL-C levels were associated with lower CHD risks in nondiabetics, but higher risks in diabetics. Smaller HDL-P was negatively, whereas very large HDL-P was positively associated with CHD risk in diabetics. These data advance our knowledge about the interactions between HDL and diabetes.

Amplifying Radiotherapy by Evoking Mitochondrial Oxidative Stress Using a High-performance Aggregation-induced Emission Sonosensitizer.

INTRODUCTION: Developing effective methods to enhance tumor radiosensitivity is crucial for improving the therapeutic efficacy of radiotherapy (RT). Due to its deep tissue penetration, excellent safety profile, and precise controllability, sonosensitizer- based sonodynamic therapy (SDT) has recently garnered significant attention as a promising combined approach with RT. METHOD: However, the limited reactive oxygen species (ROS) generation ability in the aggregated state and the absence of specific organelle targeting in sonosensitizers hinder their potential to augment RT. This study introduces a fundamental principle guiding the design of high-performance sonosensitizers employed in the aggregated state. Building upon these principles, we develop a mitochondria-targeted sonosensitizer molecule (TCSVP) with aggregation-induced emission (AIE) characteristics by organic synthesis. Then, we demonstrate the abilities of TCSVP to target mitochondria and produce ROS under ultrasound in H460 cancer cells using confocal laser scanning microscopy (CLSM) and fluorescence microscopy. Subsequently, we examine the effectiveness of enhancing tumor radiosensitivity by utilizing TCSVP and ultrasound in both H460 cells and H460 and 4T1 tumor-bearing mice. RESULTS: The results indicate that evoking non-lethal mitochondrial oxidative stress in tumors by TCSVP under ultrasound stimulation can significantly improve tumor radiosensitivity (p <0.05). Additionally, the in vivo safety profile of TCSVP is thoroughly confirmed by histopathological analysis. CONCLUSION: This work proposes strategies for designing efficient sonosensitizers and underscores that evoking non-lethal mitochondrial oxidative stress is an effective method to enhance tumor radiosensitivity.

Accelerating catalytic conversion and chemisorption of polysulfides for advanced Li-S batteries from incorporating Fe0.64Ni0.36@Co5.47N hetero-nanocrystals into boron carbonitride nanotubes.

With the rapid development of large-scale clean energy, lithium-sulfur (Li-S) batteries are considered to be one of the most promising energy storage devices. In this manuscript, the polymetallic hetero-nanocrystal of iron nickel@cobalt nitride encapsulating into boron carbonitride nanotubes (Fe0.64Ni0.36@Co5.47N@BCN) was designed and optimized for use as a modified material for commercial polypropylene (PP) separators. The prepared Fe0.64Ni0.36@Co5.47N@BCN-12 hybrid material presents strong chemisorption and catalytic conversion capabilities, which endows the Fe0.64Ni0.36@Co5.47N@BCN-12//PP separator with enhanced polysulfide shuttling inhibition. The assembled Li-S cells with Fe0.64Ni0.36@Co5.47N@BCN-12//PP separators have minimized charge transfer resistance and faster redox kinetics. Additionally, cells with Fe0.64Ni0.36@Co5.47N@BCN-12//PP separator provide high reversible capacity of 674 mAh/g for 400 cycles at 0.5C and excellent cyclability for 1000 cycles at 2C with a low decay rate of 0.05 % per cycle. Therefore, this study provides a feasible functionalization route for improving the electrochemical performance of Li-S batteries through separator modification.

Association between Dietary Acid Load and Chronic Kidney Disease in the Chinese Population: A Comprehensive Analysis of the China Health and Nutrition Survey (2009).

BACKGROUND: Dietary acid load (DAL) is closely related to several chronic diseases. However, the link between DAL and chronic kidney disease (CKD) remains scarce and without data from the Chinese populations whose diet is quite different from people in Western countries. METHODS: This study evaluated DAL by potential renal acid load (PRAL) and net endogenous acid production (NEAP). We clarified the relationship between DAL and CKD by logistic regression analysis based on data from the China Health and Nutrition Survey (CHNS). RESULTS: The final analysis included 7699 individuals, of whom 811 (11.44%) were CKD patients. Although there was no notable link between PRAL and CKD, higher NEAP levels were independently correlated with CKD. As NEAP values rise, so does CKD prevalence. This trend remains highly significant even after adjustments. In subgroup analyses, the relationship between NEAP and CKD was more consistent in the elderly and subjects with a waistline of less than 82 cm and those without diabetes and heart disease. RCS analysis further confirmed the clear linear relationship between the OR of CKD and NEAP score. CONCLUSIONS: This study highlighted that higher NEAP was positively correlated with the risk of CKD.

Discovery and validation of a 10-gene predictive signature for response to adjuvant chemotherapy in stage II and III colon cancer.

Identifying patients with stage II and III colon cancer who will benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy is crucial for the advancement of personalized cancer therapy. We employ a semi-supervised machine learning approach to analyze a large dataset with 933 stage II and III colon cancer samples. Our analysis leverages gene regulatory networks to discover an 18-gene prognostic signature and to explore a 10-gene signature that potentially predicts chemotherapy benefits. The 10-gene signature demonstrates strong prognostic power and shows promising potential to predict chemotherapy benefits. We establish a robust clinical assay on the NanoString nCounter platform, validated in a retrospective formalin-fixed paraffin-embedded (FFPE) cohort, which represents an important step toward clinical application. Our study lays the groundwork for improving adjuvant chemotherapy and potentially expanding into immunotherapy decision-making in colon cancer. Future prospective studies are needed to validate and establish the clinical utility of the 10-gene signature in clinical settings.

Adherence to a planetary health diet, genetic susceptibility, and incident cardiovascular disease: a prospective cohort study from the UK Biobank.

BACKGROUND: The influence of adherence to a planetary health diet (PHD) proposed by the EAT-Lancet Commission on cardiovascular disease (CVD) is inconclusive. Besides, whether genetic susceptibility to CVD can modify the association of PHD with CVD remains unknown. OBJECTIVE: We aimed to investigate the association between adherence to PHD and CVD, and to evaluate the interaction between PHD and genetic predisposition to CVD. METHODS: This study included 114,165 participants who completed at least two 24-h dietary recalls and were initially free of CVD from the UK Biobank. PHD score was calculated to assess adherence to PHD. Genetic risk was evaluated using the polygenic risk score. Incidence of total CVD, ischemic heart disease (IHD), atrial fibrillation (AF), heart failure (HF), and stroke were identified via electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.9 y, 10,071 (8.8%) incident CVD cases were documented. Compared with participants with the lowest adherence to PHD, HRs (95% CIs) for total CVD, IHD, AF, HF, and stroke among those with the highest adherence were 0.79 (0.74, 0.84), 0.73 (0.67, 0.79), 0.90 (0.82, 0.99), 0.69 (0.59, 0.82), and 0.88 (0.75, 1.04), respectively. No significant interaction between the genetic risk of CVD and PHD was observed. Participants with high genetic risk and low PHD score, as compared with those with low genetic risk and high PHD score, had a 48% (95% CI: 40%, 56%) higher risk of CVD. The population-attributable risk (95% CI) of CVD for poor adherence to PHD ranged from 8.79% (5.36%, 12.51%) to 14.00% (9.00%, 18.88%). CONCLUSIONS: These findings suggest that higher adherence to PHD was associated with lower risk of total CVD, IHD, AF, and HF in populations across all genetic risk categories.

Association of ultraprocessed food consumption with risk of microvascular complications among individuals with type 2 diabetes in the UK Biobank: a prospective cohort study.

BACKGROUND: The poor nutritional characteristics and potentially harmful molecules in ultraprocessed foods (UPFs) are risk factors for diabetic microvascular complications. However, the evidence regarding UPFs and diabetic microvascular complications remains limited. OBJECTIVES: We aimed to evaluate the associations between UPF consumption and risk of diabetic microvascular complications, to examine the underlying biological pathways (e.g., inflammation and lipid profile), and to identify whether the associations differ by type of UPF dietary patterns. METHODS: We included a prospective cohort of UK Biobank participants with type 2 diabetes (T2D) having at least one 24-h dietary recall (N = 5685). UPFs were defined using the Nova classification. Principal component analysis was used to derive UPF consumption patterns. Associations of UPFs and their consumption patterns with microvascular complications were assessed using Cox proportional hazards regression models. Mediation analyses were used to estimate the mediating effects of 22 biomarkers. RESULTS: During a median of 12.7 y of follow-up, 1243 composite microvascular complications events occurred (599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events). Five consumption patterns were identified (spread and bread, cereal prepared with liquids, dairy-based products, sugary beverage and snack, and mixed beverage and savory snack patterns). A 10% increment in the proportion of UPF was associated with higher hazards of the composite microvascular complications (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.03, 1.13) and diabetic kidney disease (HR: 1.13; 95% CI: 1.06, 1.20). Triglycerides, C-reactive protein, and body mass index collectively explained 22.0% (9.6%-43.0%) of the association between UPF intake and composite microvascular complications. Pattern high in mixed beverage and savory snack was associated with a higher risk of composite microvascular complications. CONCLUSIONS: Higher UPF consumption was associated with higher risks of diabetic microvascular complications, and the association was partly mediated through multiple potential ways.

Mechanism of N2O formation in catalytic after-treatment systems of ammonia/hydrogen-fuelled engines.

The combustion processes and catalytic after-treatment of ammonia/hydrogen-fueled engines, including NOx storage and reduction (NSR) and noble-metal selective catalytic reduction (SCR), can produce the byproduct N2O, a potent greenhouse gas that weakens the zero-carbon attribute of these fuels. Currently, the mechanism of N2O formation on DeNOx catalysts remains unclear due to limited research on catalytic after-treatment for such engines and the complexity of surface catalytic reactions. To elucidate the formation of N2O on the DeNOx catalysts of ammonia/hydrogen fuel engines, the impact factors on N2O formation on platinum catalysts (typical catalysts in NSR and noble-metal SCR) were investigated using first-principles molecular dynamics (FPMD). By employing the blue-moon ensemble enhanced sampling method and the slow-growth approach for free energy surface exploration, together with density functional theory (DFT) for electronic structure analysis, a linear relationship between the spin splitting of the d states of Pt clusters and N2O formation energy barriers was revealed, along with the increased structural sensitivity of Pt clusters with fewer atoms. It is highlighted that the energy barrier for N2O formation is determined by the matching degree of energy levels between molecules and surfaces. These findings provide atomic-scale insights into N2O formation on DeNOx catalysts for ammonia/hydrogen-fueled engines, facilitating N2O emission control for carbon-free engines.

Case report and literature review: management of Paxlovid (nirmatrelvir/ritonavir)-induced acute tacrolimus toxicity in a patient with systemic lupus erythematosus.

Despite the availability of effective vaccines and treatments for SARS-CoV-2, managing COVID-19 in patients with systemic lupus erythematosus (SLE) remains challenging, particularly considering drug-drug interactions (DDIs). Here, we present a case of DDIs between Tacrolimus (Tac) and nirmatrelvir/ritonavir (NMV/r) in a 32-year-old male with SLE. Following self-administration of NMV/r and resumption of Tac after 5 days, the patient experienced acute nephrotoxicity and neurotoxicity, accompanied by supratherapeutic Tac levels, despite Tac being withheld during NMV/r. The primary cause of this acute toxicity is attributed to ritonavir's inhibitory effect on both CYP3A4 enzymes and P-glycoprotein. Upon admission, Tac was discontinued, and supportive therapies were initiated. Phenytoin, a CYP3A4 inducer, was administered to lower Tac levels under the guidance of clinical pharmacists, effectively alleviating the patient's acute toxic symptoms. The half-life of Tac during the treatment of phenytoin was calculated to be 55.87 h. And no adverse reactions to phenytoin were observed. This case underscores the persistence of enzyme inhibition effects and demonstrates the effectiveness and safety of utilizing CYP3A4 enzyme inducers to mitigate Tac concentrations. Furthermore, it emphasizes the importance of healthcare providers and patients being vigilant about DDIs in Tac recipients. Lastly, it highlights the indispensable role of pharmacist involvement in clinical decision-making and close monitoring in complex clinical scenarios. Although our findings are based on a single case, they align with current knowledge and suggest the potential of individualized combination therapy in managing challenging COVID-19 cases in immunocompromised patients.

Tensile force field plays a crucial role in local invasion of tumor cells through a mechano-chemical coupling mechanism.

Cancer metastasis starts from early local invasion, during which tumor cells detach from the primary tumor, penetrate the extracellular matrix (ECM), and then invade neighboring tissues. However, the cellular mechanics in the detaching and penetrating processes have not been fully understood, and the underlying mechanisms that influence cell polarization and migration in the 3D matrix during tumor invasion remain largely unknown. In this study, we employed a dual tumor-spheroid model to investigate the cellular mechanisms of the tumor invasion. Our results revealed that the tensional force field developed by the active contraction of cells and tissues played a pivotal role in tumor invasion, acting as the driving force for remodeling the collagen fibers during the invasion process. The remodeled collagen fibers promoted cell polarization and migration because of the stiffening of the fiber matrix. The aligned fibers facilitated tumor cell invasion and directed migration from one spheroid to the other. Inhibiting/shielding the cellular contractility abolished matrix remodeling and re-alignment and significantly decreased tumor cell invasion. By developing a coarse-grained cell model that considers the mutual interaction between cells and fibers, we predicted the tensional force field in the fiber network and the associated cell polarization and cell-matrix interaction during cell invasion, which revealed a mechano-chemical coupling mechanism at the cellular level of the tumor invasion process. Our study highlights the roles of cellular mechanics at the early stage of tumor metastasis and may provide new therapeutic strategies for cancer therapy.

Oxidative Difunctionalization of N-Aryl Bicyclobutyl Amides with Aldehydes: Divergent Synthesis of Acylated and Alkylated 3-Spirocyclobutyl Oxindoles.

An efficient and operationally simple oxidative radical difunctionalization of N-aryl bicyclobutyl (BCB) amides with aldehydes is described. It was found that acylated 3-spirocyclobutyl oxindoles were generated from the coupling of BCB-amides and aromatic aldehydes, while reactions gave exclusively decarbonylative alkylarylation products using alkyl aldehydes as radical precursors.

Systematic investigation on the rational design and optimization of bi-based metal oxide semiconductors in photocatalytic applications.

To address the global energy shortage and mitigate greenhouse gas emissions on a massive scale, it is critical to explore novel and efficient photocatalysts for the utilization of renewable resources. Bi-based metal oxide (BixMOy) semiconductors composed of bismuth, transition metal, and oxygen atoms have demonstrated improved photocatalytic activity and product selectivity. The vast number of element combinations available for BixMOymaterials provides a huge compositional space for the rational design and isolation of promising photocatalysts for specific applications. In this study, we have systematically investigated the electronic and optical properties over Bi2O3and a series of selected BixMOygroup materials (BiVO4, BiFeO3, BiCoO3, and BiCrO3) by calculating band structure, basic optical property features, mobility and separation of charge carriers. It is clearly noted that the band gap and band edge position of the BixMOygroup materials can be tuned in a wide range in comparison to Bi2O3. Similarly, the light response of BixMOyalso can be broadened from the ultraviolet to the visible light region by adjusting the selection of transition metals. Additionally, the analysis of the effective mass of charge carriers of these materials further confirms their possibility in photocatalytic reaction applications because of the appropriate separation efficiency and mobility of carriers. A selection of experimental investigations on the crystal structure, composition, and optical properties of Bi2O3, BiVO4, and BiFeO3as well as their catalytic performance in the degradation of methylene blue over was also conducted, which agree well with the theoretical predictions.

Blue valorization of lignin-derived monomers via reprogramming marine bacterium Roseovarius nubinhibens.

Biological valorization of lignin, the second most abundant biopolymer on Earth, is an indispensable sector to build a circular economy and net-zero future. However, lignin is recalcitrant to bioupcycling, demanding innovative solutions. We report here the biological valorization of lignin-derived aromatic carbon to value-added chemicals without requesting extra organic carbon and freshwater via reprogramming the marine Roseobacter clade bacterium Roseovarius nubinhibens. We discovered the unusual advantages of this strain for the oxidation of lignin monomers and implemented a CRISPR interference (CRISPRi) system with the lacI-Ptrc inducible module, nuclease-deactivated Cas9, and programmable gRNAs. This is the first CRISPR-based regulatory system in R. nubinhibens, enabling precise and efficient repression of genes of interest. By deploying the customized CRISPRi, we reprogrammed the carbon flux from a lignin monomer, 4-hydroxybenzoate, to achieve the maximum production of protocatechuate, a pharmaceutical compound with antibacterial, antioxidant, and anticancer properties, with minimal carbon to maintain cell growth and drive biocatalysis. As a result, we achieved a 4.89-fold increase in protocatechuate yield with a dual-targeting CRISPRi system, and the system was demonstrated with real seawater. Our work underscores the power of CRISPRi in exploiting novel microbial chassis and will accelerate the development of marine synthetic biology. Meanwhile, the introduction of a new-to-the-field lineage of marine bacteria unveils the potential of blue biotechnology leveraging resources from the ocean.IMPORTANCEOne often overlooked sector in carbon-conservative biotechnology is the water resource that sustains these enabling technologies. Similar to the "food-versus-fuel" debate, the competition of freshwater between human demands and bioproduction is another controversial issue, especially under global water scarcity. Here, we bring a new-to-the-field lineage of marine bacteria with unusual advantages to the stage of engineering biology for simultaneous carbon and water conservation. We report the valorization of lignin monomers to pharmaceutical compounds without requesting extra organic substrate (e.g., glucose) or freshwater by reprogramming the marine bacterium Roseovarius nubinhibens with a multiplex CRISPR interference system. Beyond the blue lignin valorization, we present a proof-of-principle of leveraging marine bacteria and engineering biology for a sustainable future.

Ultrasound-targeted microbubble destruction facilitates cartilage repair through increased the migration of mesenchymal stem cells via HIF-1α-mediated glycolysis pathway in rats.

OBJECTIVE: Mesenchymal stem cells (MSCs) can treat osteoarthritis (OA), but their therapeutic efficacy is poor to date due to low migration efficiency. This study aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) could ameliorate cartilage repair efficiency through facilitating the migration of MSCs via hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis regulatory pathway in OA model rats. METHODS: OA rats were treated with MSCs alone or in combination with UTMD, respectively, for 4 weeks. Cartilage histopathology, MSCs migration efficiency, von Frey fiber thresholds, and the expression levels of collagen II and MMP-13 were measured. Further, MSCs were extracted from the bone marrow of rats, cocultured with osteoarthritic chondrocytes, transfected to siRNA-HIF-1α, and subjected to UTMD for 4 days. Glucose consumption, lactate production, and cell migration efficiency were assessed. The protein expression levels of HIF-1α, HK2, PKM2, and GLUT1 were measured, respectively. RESULTS: In OA rat model, NC-MSCs + UTMD improved migration efficiency, increased collagen II expression, decreased MMP-13 expression, and delayed osteoarthritis progression. Silencing HIF-1α attenuated the effects induced by UTMD. In vitro, UTMD led to increases in MSC activity and migration, glucose consumption, lactate production, and the protein expression of HIF-1α, HK2, PKM2, and GLUT1 expression, all of which were reversed upon HIF-1α silencing. CONCLUSION: UTMD enhances MSCs migration and improves cartilage repair efficiency through the HIF-1α-mediated glycolytic regulatory pathway, providing a novel therapy strategy for knee osteoarthritis.