CD34+ stromal cells/telocytes and their role in mouse lung development: Light microscopy, immunofluorescence, ultrastructural and scanning electron microscopy evidence.

Telocytes (TCs), a novel type of mesenchymal or interstitial cell with specific, very long and thin cellular prolongations, have been found in various mammalian organs and have potential biological functions. However, their existence during lung development is poorly understood. This study aimed to investigate the existence, morphological features, and role of CD34+ SCs/TCs in mouse lungs from foetal to postnatal life using primary cell culture, double immunofluorescence, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The immunofluorescence double staining profiles revealed positive expression of CD34 and PDGFR-α, Sca-1 or VEGFR-3, and the expression of these markers differed among the age groups during lung development. Intriguingly, in the E18.5 stage of development, along with the CD34+ SCs/TCs, haematopoietic stem cells and angiogenic factors were also significantly increased in number compared with those in the E14.5, E16.5, P0 and P7. Subsequently, TEM confirmed that CD34+ SCs/TCs consisted of a small cell body with long telopodes (Tps) that projected from the cytoplasm. Tps consisted of alternating thin and thick segments known as podomers and podoms. TCs contain abundant endoplasmic reticulum, mitochondria and secretory vesicles and establish close connections with neighbouring cells. Furthermore, SEM revealed characteristic features, including triangular, oval, spherical, or fusiform cell bodies with extensive cellular prolongations, depending on the number of Tps. Our findings provide evidence for the existence of CD34+ SCs/TCs, which contribute to vasculogenesis, the formation of the air‒blood barrier, tissue organization during lung development and homoeostasis.

Acidity-Responsive Fe-PDA@CaCO3 Nanoparticles for Photothermal-Enhanced Calcium-Overload- and Reactive-Oxygen-Species-Mediated Tumor Therapy.

Calcium-overload-mediated tumor therapy has received considerable interest in oncology. However, its efficacy has been proven to be inadequate due to insufficient calcium ion concentration at the tumor site coupled with challenges in facilitating efficient calcium uptake by tumors, leading to unsatisfactory therapeutic outcomes. In the present study, calcium carbonate nanoshell mineralized ferric polydopamine nanoparticles (Fe-PDA@CaCO3 NPs) were prepared for achieving Ca2+-overload-mediated tumor therapy. Upon entering the tumor site, the pH-responsive CaCO3 layer, acting as a "Ca2+ storage pool", rapidly degraded and released high quantities of free Ca2+ within the weakly acidic environment. The Fe-PDA core, with its excellent photothermal conversion properties, could significantly increase the temperature upon exposure to near-infrared (NIR) light irradiation, thereby activating the TRPV1 channel and leading to a large influx of released Ca2+ into the cytoplasm. Furthermore, the exposed Fe-PDA core could react with the tumor-overexpressed hydrogen peroxide (H2O2) to efficiently produce hydroxyl radicals (•OH), significantly increasing intracellular reactive oxygen species (ROS) levels and thus inhibiting the activity of the Ca2+ efflux pump, resulting in a high intracellular Ca2+ concentration. Ultimately, the increase in calcium/ROS levels could disrupt mitochondrial homeostasis and activate the apoptosis pathway. The current work presents a promising approach for tumor therapy using photothermal-enhanced calcium-overload-mediated ion interference therapy and chemodynamic therapy.

Solidify Eutectic Electrolytes via the Added MXene as Nucleation Sites for a Solid-State Zinc-Ion Battery with Reconstructed Ion Transport.

Stationary energy storage infrastructure based on zinc-ion transport and storage chemistry is attracting more attention due to favorable metrics, including cost, safety, and recycling feasibility. However, splitting water and liquid electrolyte fluidity lead to cathode dissolution and Zn corrosion, resulting in rapid attenuation of the capacity and service life. Herein, a new architecture of solid-state electrolytes with high zinc ionic conductivity at room temperature was prepared via solidification of deep eutectic solvents utilizing MXene as nucleation additives. The ionic conductivity of MXene/ZCEs reached 6.69 × 10-4 S cm-1 at room temperature. Dendrite-free Zn plating/stripping with high reversibility can remain for over 2500 h. Subsequently, the fabricated solid-state zinc-ion battery with eliminated HER and suppressed Zn dendrites exhibited excellent cycling performance and could work normally in a range from -10 to 60 °C. This design inspired by eutectic solidification affords new insights into the multivalent solid electrochemistry suffering from slow ion migration.

Constructing CoP/Ni2P Heterostructure Confined Ru Sub-Nanoclusters for Enhanced Water Splitting in Wide pH Conditions.

Developing efficient electrocatalysts for water splitting is of great significance for realizing sustainable energy conversion. In this work, Ru sub-nanoclusters anchored on cobalt-nickel bimetallic phosphides (Ru-CoP/Ni2P) are constructed by an interfacial confinement strategy. Remarkably, Ru-CoP/Ni2P with low noble metal loading (33.1 µg cm-2) shows superior activity for hydrogen evolution reaction (HER) in all pH values, whose turnover frequency (TOF) is 8.7, 15.3, and 124.7 times higher than that of Pt/C in acidic, alkaline, and neutral conditions, respectively. Meanwhile, it only requires the overpotential of 171 mV@10 mA cm-2 for oxygen evolution reaction (OER) and corresponding TOF is 20.3 times higher than that of RuO2. More importantly, the Ru-CoP/Ni2P||Ru-CoP/Ni2P displays superior mass activity of 4017 mA mgnoble metal -1 at 2.0 V in flowing alkaline water electrolyzer, which is 105.1 times higher than that of Pt/C||IrO2. In situ Raman spectroscopy demonstrates that the Ru sites in Ru-CoP/Ni2P play a key role for water splitting and follow the adsorption evolution mechanism toward OER. Further mechanism studies disclose the confined Ru atom contributes to the desorption of H2 during HER and the formation of O-O bond during OER, leading to fast reaction kinetics. This study emphasizes the importance of interface confinement for enhancing electrocatalytic activity.

High catalytic activity and abundant active sites in M2C12 monolayer for nitrogen reduction reaction.

Developing highly efficient single-atom catalysts (SACs) for the nitrogen reduction reaction (NRR) to ammonia production has garnered significant attention in the scientific community. However, achieving high activity and selectivity remains challenging due to the lack of innate activity in most existing catalysts or insufficient active site density. This study delves into the potential of M2C12 materials (M = Cr, Ir, Mn, Mo, Os, Re, Rh, Ru, W, Fe, Cu, and Ti) with high transition metal coverage as SACs for NRR using first-principles calculations. Among these materials, Os2C12 exhibited superior catalytic activity for NRR, with a low overpotential of 0.39 V and an Os coverage of up to 72.53 wt%. To further boost its catalytic activity, a nonmetal (NM) atom doping (NM = B, N, O, and S) and C vacancy modification were explored in Os2C12. It is found that the introduction of O enables exceptional catalytic activity, selectivity, and stability, with an even lower overpotential of 0.07 V. Incorporating the O atom disrupted the charge balance of its coordinating C atoms, effectively increasing the positive charge density of the Os-d-orbit-related electronic structure. This promoted strong d-π* coupling between Os and N2H, enhancing N2H adsorption and facilitating NRR processes. This comprehensive study provides valuable insights into NRR catalyst design for sustainable ammonia production and offers a reference for exploring alternative materials in other catalytic reactions.

[Microbial metaproteomics--From sample processing to data acquisition and analysis].

Microorganisms are closely associated with human diseases and health. Understanding the composition and function of microbial communities requires extensive research. Metaproteomics has recently become an important method for throughout and in-depth study of microorganisms. However, major challenges in terms of sample processing, mass spectrometric data acquisition, and data analysis limit the development of metaproteomics owing to the complexity and high heterogeneity of microbial community samples. In metaproteomic analysis, optimizing the preprocessing method for different types of samples and adopting different microbial isolation, enrichment, extraction, and lysis schemes are often necessary. Similar to those for single-species proteomics, the mass spectrometric data acquisition modes for metaproteomics include data-dependent acquisition (DDA) and data-independent acquisition (DIA). DIA can collect comprehensive peptide information from a sample and holds great potential for future development. However, data analysis for DIA is challenged by the complexity of metaproteome samples, which hinders the deeper coverage of metaproteomes. The most important step in data analysis is the construction of a protein sequence database. The size and completeness of the database strongly influence not only the number of identifications, but also analyses at the species and functional levels. The current gold standard for metaproteome database construction is the metagenomic sequencing-based protein sequence database. A public database-filtering method based on an iterative database search has been proven to have strong practical value. The peptide-centric DIA data analysis method is a mainstream data analysis strategy. The development of deep learning and artificial intelligence will greatly promote the accuracy, coverage, and speed of metaproteomic analysis. In terms of downstream bioinformatics analysis, a series of annotation tools that can perform species annotation at the protein, peptide, and gene levels has been developed in recent years to determine the composition of microbial communities. The functional analysis of microbial communities is a unique feature of metaproteomics compared with other omics approaches. Metaproteomics has become an important component of the multi-omics analysis of microbial communities, and has great development potential in terms of depth of coverage, sensitivity of detection, and completeness of data analysis.

Intraparticle Electron Transfer for Long-Lasting Tumor Chemodynamic Therapy.

Chemodynamic therapy (CDT) is a novel tumor treatment method by using hydroxyl radicals (•OH) to kill cancer cells. However, its therapeutic effects are strictly confined by the short lifespan of •OH and reduced •OH generation speed. Herein, an effective CDT is achieved by both improving •OH lifetime and long-lasting generating •OH through intraparticle electron transfer within heterogeneous nanoparticles (NPs). These heterogeneous NPs are composed of evenly distributed Cu and Fe3O4 (CFO NPs) with large interaction interfaces, and electrons tend to transfer from Cu to Fe3O4 for the appearance of ≡Cu2+ and increase in ≡Fe2+. The generated ≡Cu2+ can interact with GSH, which prolongs the lifespan of •OH, produces ≡Cu+ for higher speed •OH generation with H2O2, and induces cell ferroptosis for tumor therapy. The improved ≡Fe2+ can also improve the •OH release under H2O2 until Cu is depleted. As a result, a sustainable •OH generation is achieved to promote cell apoptosis for effective tumor therapy. Since H2O2 and GSH are only overexpressed at tumor, and CFO NPs can degrade in the tumor microenvironment, these NPs are with high biosafety and can be metabolized by urine. This work provides a novel biomaterial for effective cancer CDT through intraparticle electron transfer.

The Applicability of Polyetheretherketone and Titanium Mesh in Cranioplasty: A Retrospective Comparative Analysis.

OBJECTIVE: To compare the clinical application effect and safety of polyetheretherketone (PEEK) and titanium mesh (TM) in cranioplasty. METHODS: Four-year retrospective comparison of patients (96 cases) undergoing synthetic cranioplasty with PEEK or TM. The patients were divided into the PEEK group (24 cases) and the TM group (72 cases) according to the implants, and the patient demographics, general conditions before the operation, postoperative complications, length of postoperative hospital stay, total costs, satisfaction with shaping and long-term complications were compared between the 2 groups. RESULTS: Patients in the PEEK group were younger than those in the TM group (P=0.019). Hospitalization costs were significantly higher in the PEEK group than in the TM group (P<0.001). The incidence of postoperative subcutaneous effusion was 33% in the PEEK group and 6.9% in the TM group, which suggests that patients in the PEEK group had a higher risk of postoperative subcutaneous effusion (P=0.001). There was no significant difference in the incidence of long-term complications and cosmetic satisfaction between the 2 groups at 4 years postoperatively. CONCLUSIONS: In this study, both titanium mesh and PEEK are reliable implants for cranioplasty. Titanium mesh is widely used in cranioplasty due to its cost-effective performance. PEEK has gradually gained recognition due to the characteristics of the material and surgical procedure, but the price needs to be further reduced, and attention should be paid to the occurrence and treatment of early postoperative subcutaneous effusion.

Novel multi-functional microsphere scaffold with shape memory function for bone regeneration.

Irregular bone defects caused by trauma and bone diseases provide a complex implant environment for surgery. Traditional implants often fail to integrate well with the surrounding bone defect interface, therefore, developing an artificial bone scaffold that can adapt to irregular bone defect boundaries is of significant importance for bone defect repair. This study successfully utilized a shape memory ternary copolymer polylactic acid-trimethylene carbonate-hydroxyacetic acid (PLLA-TMC-GA) and dopamine-modified nano-hydroxyapatite (PHA) composite to construct a temperature-responsive bone repair scaffold (PTG/PHA), thereby enhancing the interface compatibility between the implant and the surrounding environment. The addition of PHA has effectively improved the hydrophilicity of the stent and significantly increased its mechanical strength. Furthermore, the Sodium alginate (SA) hydrogel loaded with Icariin (Ica) coated on the stent surface promotes the growth and differentiation of bone cells through the drug-scaffold synergistic effect. Both in vivo and in vitro experiments have shown that the synergistic effect of the composite stent with Icariin significantly enhances the repair of bone defects. This study provides a promising tissue engineering method for the repair of irregular bone defects.

Hypervalent Iodine Promoted Selective [2 + 2 + 1] Cycloaddition of Aromatic Ketones and Methylamines: A One-Pot Access to 1-Pyrrolines.

Herein, a versatile highly regioselective three-component annulation of simple aromatic ketones and methylamines using a hypervalent iodine reagent for polyarylated 1-pyrrolines has been described in good to excellent yields. Meanwhile, unsymmetrical 1-pyrroline isomers could be realized and synthesized. Such an intriguing one-pot two-step tandem assembly strategy with green conditions and high regioselectivity shows predictable inspiration in related annulation reactions.

Pt-N catalytic centres concisely enhance interfacial charge transfer in amines functionalized Pt@MOFs for selective conversion of CO2 to CH4.

Improving ligand-to-active metal charge transfer (LAMCT) by finely tuning the organic ligand is a decisive strategy to enhance charge transfer in metal organic frameworks (MOFs)-based catalysts. However, in most MOFs loaded with active metal catalysts, electron transmission encounters massive obstacle at the interface between the two constituents owing to poor LAMCT. Herein, amines (-NH2) functionalized MOFs (NH2-MIL-101(Cr)) encapsulated active metal Pt nanoclusters (NCs) catalysts are synthesized by the polyol reduction method and utilized for the photoreduction of CO2. Surprisingly, the introduction of -NH2 (electron donating) groups within the matrix of MIL-101(Cr) improved the electron migration through the LAMCT process, fostering a synergistic interaction with Pt. The combined experimental analysis exposed the high number of metallic Pt (Pt0) in Pt@NH2-MIL-101(Cr) catalyst through seamless electron shuttling from N of -NH2 group to excited Pt generating versatile hybrid Pt-N catalytic centres. Consequently, these versatile hybrid catalytic centres act as electro-nucleophilic centres, which enable the efficient and selective conversion of CO bond in CO2 to harvest CH4 (131.0 µmol.g-1) and maintain excellent stability and selectivity for consecutive five rounds, superior to Pt@MIL-101(Cr) and most reported catalysts. Our study verified that the precise tuning of organic ligands in MOFs immensely improves the surface-active centres, electron migration, and catalytic selectivity of the excited Pt NCs catalysts encaged inside MOFs through an improved LAMCT pathway.

Proteomic and metabolic analysis of Moorella thermoacetica-g-C3N4 nanocomposite system for artificial photosynthesis.

Artificial photosynthesis by microbe-semiconductor biohybrid systems has been demonstrated as a valuable strategy in providing sustainable energy and in carbon fixation. However, most of the developed biohybrid systems for light harvesting employ heavy metal materials, especially cadmium sulfide (CdS), which normally cause environmental pollution and restrict the widespread of the systems. Herein, we constructed an environmentally friendly biohybirid system based on a typical acetogenic bacteria, Moorella thermoacetica, coupling with a carbon-based semiconductor, graphitic carbon nitride (g-C3N4), to realize light-driven carbon fixation. The proposed biohybrid system displayed outstanding acetate productivity with a quantum yield of 2.66 ± 0.43 %. Non-targeted proteomic analysis indicated that the physiological activity of the bacteria was improved, coupling with the non-toxic material. We further proposed the mechanisms of energy generation, electron transfer and CO2 fixation of the irradiated biohybrid system by proteomic and metabolomic characterization. With the photoelectron generated in g-C3N4 under illumination, CO2 is finally converted to acetate via the Wood-Ljungdahl pathway (WLP). Other associated pathways were also proved to be activated, providing extra energy or substrates for acetate production. The study reveals that the future focus of the development of biohybrid systems for light harvesting can be on the metal-free biocompatible material, which can activate the expression of the key enzymes involved in the electron transfer and carbon metabolism under light irradiation.

[Impact of anemia on incidence of perioperative lower limb deep vein thrombosis in patients undergoing total hip arthroplasty].

Objective: To explore the impact of anemia on the incidence of perioperative lower limb deep vein thrombosis (DVT) in patients undergoing total hip arthroplasty (THA). Methods: A retrospective analysis was conducted on clinical data of 1 916 non-fracture patients who underwent THA between September 2015 and December 2021, meeting the selection criteria. Among them, there were 811 male and 1 105 female patients, aged between 18 and 94 years with an average of 59.2 years. Among the patients, 213 were diagnosed with anemia, while 1 703 were not. Preoperative DVT was observed in 55 patients, while 1 861 patients did not have DVT preoperatively (of which 75 patients developed new-onset DVT postoperatively). Univariate analysis was performed on variables including age, gender, body mass index (BMI), diabetes, hypertension, history of tumors, history of thrombosis, history of smoking, revision surgery, preoperative D-dimer positivity (≥0.5 mg/L), presence of anemia, operation time, intraoperative blood loss, transfusion requirement, and pre- and post-operative levels of red blood cells, hemoglobin, hematocrit, and platelets. Furthermore, logistic regression was utilized for multivariate analysis to identify risk factors associated with DVT formation. Results: Univariate analysis showed that age, gender, hypertension, revision surgery, preoperative levels of red blood cells, preoperative hemoglobin, preoperative D-dimer positivity, and anemia were influencing factors for preoperative DVT ( P<0.05). Further logistic regression analysis indicated that age (>60 years old), female, preoperative D-dimer positivity, and anemia were risk factors for preoperative DVT ( P<0.05). Univariate analysis also revealed that age, female, revision surgery, preoperative D-dimer positivity, anemia, transfusion requirement, postoperative level of red blood cells, and postoperative hemoglobin level were influencing factors for postoperative new-onset DVT ( P<0.05). Further logistic regression analysis indicated that age (>60 years old), female, and revision surgery were risk factors for postoperative new-onset DVT ( P<0.05). Conclusion: The incidence of anemia is higher among patients with preoperative DVT for THA, and anemia is an independent risk factor for preoperative DVT occurrence in THA. While anemia may not be an independent risk factor for THA postoperative new-onset DVT, the incidence of anemia is higher among patients with postoperative new-onset DVT.

4D-Printed MXene-Based Artificial Nerve Guidance Conduit for Enhanced Regeneration of Peripheral Nerve Injuries.

Repairing larger defects (>5 mm) in peripheral nerve injuries (PNIs) remains a significant challenge when using traditional artificial nerve guidance conduits (NGCs). A novel approach that combines 4D printing technology with poly(L-lactide-co-trimethylene carbonate) (PLATMC) and Ti3C2Tx MXene nanosheets is proposed, thereby imparting shape memory properties to the NGCs. Upon body temperature activation, the printed sheet-like structure can quickly self-roll into a conduit-like structure, enabling optimal wrapping around nerve stumps. This design enhances nerve fixation and simplifies surgical procedures. Moreover, the integration of microchannel expertly crafted through 4D printing, along with the incorporation of MXene nanosheets, introduces electrical conductivity. This feature facilitates the guided and directional migration of nerve cells, rapidly accelerating the healing of the PNI. By leveraging these advanced technologies, the developed NGCs demonstrate remarkable potential in promoting peripheral nerve regeneration, leading to substantial improvements in muscle morphology and restored sciatic nerve function, comparable to outcomes achieved through autogenous nerve transplantation.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

Ultra-high spatio-temporal resolution imaging with parallel acquisition-readout structured illumination microscopy (PAR-SIM).

Structured illumination microscopy (SIM) has emerged as a promising super-resolution fluorescence imaging technique, offering diverse configurations and computational strategies to mitigate phototoxicity during real-time imaging of biological specimens. Traditional efforts to enhance system frame rates have concentrated on processing algorithms, like rolling reconstruction or reduced frame reconstruction, or on investments in costly sCMOS cameras with accelerated row readout rates. In this article, we introduce an approach to elevate SIM frame rates and region of interest (ROI) coverage at the hardware level, without necessitating an upsurge in camera expenses or intricate algorithms. Here, parallel acquisition-readout SIM (PAR-SIM) achieves the highest imaging speed for fluorescence imaging at currently available detector sensitivity. By using the full frame-width of the detector through synchronizing the pattern generation and image exposure-readout process, we have achieved a fundamentally stupendous information spatial-temporal flux of 132.9 MPixels · s-1, 9.6-fold that of the latest techniques, with the lowest SNR of -2.11 dB and 100 nm resolution. PAR-SIM demonstrates its proficiency in successfully reconstructing diverse cellular organelles in dual excitations, even under conditions of low signal due to ultra-short exposure times. Notably, mitochondrial dynamic tubulation and ongoing membrane fusion processes have been captured in live COS-7 cell, recorded with PAR-SIM at an impressive 408 Hz. We posit that this novel parallel exposure-readout mode not only augments SIM pattern modulation for superior frame rates but also holds the potential to benefit other complex imaging systems with a strategic controlling approach.

Elastic Properties of Low-Dimensional Single-Crystalline Dielectric Oxides through Controlled Large-Area Wrinkle Generation.

Freestanding single-crystalline SrTiO3 membranes, as high-κ dielectrics, hold significant promise as the gate dielectric in two-dimensional (2D) flexible electronics. Nevertheless, the mechanical properties of the SrTiO3 membranes, such as elasticity, remain a critical piece of the puzzle to adequately address the viability of their applications in flexible devices. Here, we report statistical analysis on plane-strain effective Young's modulus of large-area SrTiO3 membranes (5 × 5 mm2) over a series of thicknesses (from 6.5 to 32.2 nm), taking advantage of a highly efficient buckling-based method, which reveals its evident thickness-dependent behavior ranging from 46.01 to 227.17 GPa. Based on microscopic and theoretical results, we elucidate these thickness-dependent behaviors and statistical data deviation with a bilayer model, which consists of a surface layer and a bulk-like layer. The analytical results show that the ∼3.1 nm surface layer has a significant elastic softening compared to the bulk-like layer, while the extracted modulus of the bulk-like layer shows a variation of ∼40 GPa. This variation is considered as a combined contribution from oxygen deficiency presenting in SrTiO3 membranes, and the alignment between applied strain and the crystal orientation. Upon comparison of the extracted elastic properties and electrostatic control capability to those of other typical gate dielectrics, the superior performance of single-crystalline SrTiO3 membranes has been revealed in the context of flexible gate dielectrics, indicating the significant potential of their application in high-performance flexible 2D electronics.

Regorafenib with immunotherapy versus regorafenib alone as second-line treatment for hepatocellular carcinoma: A multicenter real-world study.

INTRODUCTION: Regorafenib remains the standard and widely used second-line strategy for advanced hepatocellular carcinoma (HCC). There is still a lack of large-scale multicenter real-world evidence concerning the concurrent use of regorafenib with immune checkpoint inhibitors (ICI). This study aims to evaluate whether combining regorafenib with ICI provides greater clinical benefit than regorafenib monotherapy as second-line therapy for advanced HCC under real-world circumstances. PATIENTS AND METHODS: The study included 208 patients from five medical facilities. One hundred forty-three patients received regorafenib plus ICI combination therapy, while 65 patients received regorafenib monotherapy. Propensity score matching (PSM) analysis was employed. RESULTS: The regorafenib plus ICI group demonstrated significantly higher objective response rate (24.3% vs. 10.3%, after PSM, p = 0.030) and disease control rate (79.4% vs. 50.0%, after PSM, p < 0.001) compared to the regorafenib monotherapy group based on mRECIST criteria. Median progression-free survival (7.9 vs. 3.2 months, after PSM, p < 0.001) and overall survival (25.6 vs. 16.4 months, p = 0.010, after PSM) were also considerably longer in the regorafenib plus ICI group. The incidence of Grades 3-4 treatment-related adverse events (TRAEs) was marginally greater in the regorafenib plus ICI group than in the regorafenib group (23.8% vs. 20.0%, p = 0.546). Notably, there were no instances of treatment-related mortality or emergence of new TRAEs in any treatment group. CONCLUSION: The combination of regorafenib and ICI shows potential as a viable second-line treatment for advanced HCC, exhibiting favorable efficacy while maintaining a tolerable safety profile in contrast to regorafenib monotherapy.

Facet-Dependent Oxygen Evolution Reaction Activity of IrO2 from Quantum Mechanics and Experiments.

The diversity of chemical environments present on unique crystallographic facets can drive dramatic differences in catalytic activity and the reaction mechanism. By coupling experimental investigations of five different IrO2 facets and theory, we characterize the detailed elemental steps of the surface redox processes and the rate-limiting processes for the oxygen evolution reaction (OER). The predicted complex evolution of surface adsorbates and the associated charge transfer as a function of applied potential matches well with the distinct redox features observed experimentally for the five facets. Our microkinetic model from grand canonical quantum mechanics (GC-QM) calculations demonstrates mechanistic differences between nucleophilic attack and O-O coupling across facets, providing the rates as a function of applied potential. These GC-QM calculations explain the higher OER activity observed on the (100), (001), and (110) facets and the lower activity observed for the (101) and (111) facets. This combined study with theory and experiment brings new insights into the structural features that either promote or hinder the OER activity of IrO2, which are expected to provide parallels in structural effects on other oxide surfaces.

Characterization and prevention of flame burns caused by electric bicycle battery chargers: results from a 7-year experience.

OBJECTIVE: With the recent exponential increase in express deliveries across China, the number of patients with flame burns caused by electric bicycle battery chargers (BEBBC) has markedly increased in burn units. In this study, we aimed to characterize BEBBC to systematically explore measures to prevent their occurrence. METHODS: We performed a retrospective chart review of patients with flame burns who visited the Burn Department of Rui Jin Hospital between January 2015 and December 2021. RESULTS: Sixty-three patients with BEBBC and 1412 with types of other flame burn were included in this study. Fifty-six of the 63 BEBBC cases occurred between 9 pm and 7 am. BEBBC incidents involved a higher incidence of group burn in which multiple individuals were affected. Non-local patients with BEBBC were significantly younger than their local counterparts. BEBBC had a higher mortality than types of other flame burn. CONCLUSIONS: The rising incidence of BEBBC calls for greater attention because of the associated high mortality and heavy burden on society. Enacting related legislation, disseminating information to the public, and improving treatment to control infection can help prevent BEBBC, increase its cure rate, and reduce patient mortality.