Controlling Circular RNA Encapsulation within Extracellular Vesicles for Gene Editing and Protein Replacement.

Extracellular vesicles (EVs) are a population of vesicular bodies originating from cells, and EVs have been proven to have the potential to deliver different cargos, such as RNAs. However, conventional methods are not able to encapsulate long RNAs into EVs efficiently or may compromise the integrity of EVs. In this study, we have devised a strategy to encapsulate long circRNAs (>1000 nt) into EVs by harnessing the sorting mechanisms of cells. This strategy utilizes the inherent richness of circular RNAs in EVs and a genetic engineering method to increase the cytoplasmic concentration of target circRNAs, facilitating highly efficient RNA back-splicing to drive the circularization of RNAs. This allows target circRNAs to load into EVs with high efficiency. Furthermore, we demonstrate the practical applications of this strategy, showing that these circRNAs can be delivered by EVs to recipient cells for protein expression and to mice for gene editing.

Evolution and maintenance of a large multidrug-resistant plasmid in a Salmonella enterica Typhimurium host under differing antibiotic selection pressures.

The dissemination of antibiotic resistance genes (ARGs) through plasmids is a major mechanism for the development of bacterial antimicrobial resistance. The adaptation and evolution mechanisms of multidrug-resistant (MDR) plasmids with their hosts are not fully understood. Herein, we conducted experimental evolution of a 244 kb MDR plasmid (pJXP9) under various conditions including no antibiotics and mono- or combinational drug treatments of colistin (CS), cefotaxime (CTX), and ciprofloxacin (CIP). Our results showed that long-term with or without positive selections for pJXP9, spanning approximately 600 generations, led to modifications of the plasmid-encoded MDR and conjugative transfer regions. These modifications could mitigate the fitness cost of plasmid carriage and enhance plasmid maintenance. The extent of plasmid modifications and the evolution of plasmid-encoded antibiotic resistance depended on treatment type, particularly the drug class and duration of exposure. Interestingly, prolonged exposure to mono- and combinational drugs of CS and CIP resulted in a substantial loss of the plasmid-encoded MDR region and antibiotic resistance, comparable to the selection condition without antibiotic. By contrast, combinational treatment with CTX contributed to the maintenance of the MDR region over a long period of time. Furthermore, drug selection was able to maintain and even amplify the corresponding plasmid-encoded ARGs, with co-selection of ARGs in the adjacent regions. In addition, parallel mutations in chromosomal arcA were also found to be associated with pJXP9 plasmid carriage among endpoint-evolved clones from diverse treatments. Meanwhile, arcA deletion improved the persistence of pJXP9 plasmid without drugs. Overall, our findings indicated that plasmid-borne MDR region deletion and chromosomal arcA inactivation mutation jointly contributed to co-adaptation and co-evolution between MDR IncHI2 plasmid and Salmonella Typhimurium under different drug selection pressure.IMPORTANCEThe plasmid-mediated dissemination of antibiotic resistance genes has become a significant concern for human health, even though the carriage of multidrug-resistant (MDR) plasmids is frequently associated with fitness costs for the bacterial host. However, the mechanisms by which MDR plasmids and bacterial pairs evolve plasmid-mediated antibiotic resistance in the presence of antibiotic selections are not fully understood. Herein, we conducted an experimental evolution of a large multidrug-resistant plasmid in a Salmonella enterica Typhimurium host under single and combinatorial drug selection pressures. Our results show the adaptive evolution of plasmid-encoded antibiotic resistance through alterations of the MDR region in the plasmid, in particular substantial loss of the MDR region, in response to different positive selections, especially mono- and combinational drugs of colistin and ciprofloxacin. In addition, strong parallel mutations in chromosomal arcA were associated with pJXP9 carriage in Salmonella Typhimurium from diverse treatments. Our results thus highlight promoting the loss of the plasmid's MDR region could offer an alternative approach for combating plasmid-encoded antibiotic resistance.

27.09%-efficiency silicon heterojunction back contact solar cell and going beyond.

Crystalline-silicon heterojunction back contact solar cells represent the forefront of photovoltaic technology, but encounter significant challenges in managing charge carrier recombination and transport to achieve high efficiency. In this study, we produced highly efficient heterojunction back contact solar cells with a certified efficiency of 27.09% using a laser patterning technique. Our findings indicate that recombination losses primarily arise from the hole-selective contact region and polarity boundaries. We propose solutions to these issues and establish a clear relationship between contact resistivity, series resistance, and the design of the rear-side pattern. Furthermore, we demonstrate that the wafer edge becomes the main channel for current density loss caused by carrier recombination once electrical shading around the electron-selective contact region is mitigated. With the advanced nanocrystalline passivating contact, wafer edge passivation technologies and meticulous optimization of front anti-reflection coating and rear reflector, achieving efficiencies as high as 27.7% is feasible.

Design and in vitro/in vivo evaluation of chitosan-polyvinyl alcohol copolymer material cross-linked by dynamic borate ester covalent for pregabalin film-forming delivery system.

This research introduced a novel polymer synthesized by combining chitosan and modified polyvinyl alcohol, cross-linked with boric acid using dynamic covalent bonds. The polymer was developed to formulate a pregabalin Film-forming system (FFS) for treating postherpetic neuralgia via topical application, showcasing notable skin adhesion and drug delivery properites. The chitosan-boric acid-modified polyvinyl alcohol polymer was analyzed using NMR, FTIR. The exceptional features of the optimized FFS were evaluated through rheometer, Differential scanning calorimetry (Tg = 45.98 °C), contact angle (θ = 78.62°). The elongation (60.05 ± 3.67 %), cohesion (56.94 ± 4.65 MPa) and skin adhesion (58.12 ± 2.99 kPa) of chitosan-boric acid-modified polyvinyl alcohol were found to be 5.2, 6.8, and 8.3 times higher than those of the pure chitosan film, attributed to the double network structure formed by the cross-linked reversible dynamic covalent bond. The optimized pregabalin FFS exhibited increased in vitro (86.25 ± 1.87 µg/g) and in vivo (100.42 ± 7.44 µg/g) skin retention amounts compared to in vivo oral administration (28.43 ± 4.61 µg/g). In summary, the utilization of borate ester dynamic covalent bonds in developing chitosan-based film-forming polymer proved beneficial in improving skin adhesion and topical therapeutic effectiveness, thereby mitigating the risk of systemic side effects associated with oral administration.

Dual Metallosalen-based Covalent Organic Frameworks for Artificial Photosynthetic Diluted CO2 Reduction.

Directly converting CO2 in flue gas using artificial photosynthetic technology represents a promising green approach for CO2 resource utilization. However, it remains a great challenge to achieve efficient reduction of CO2 from flue gas due to the decreased activity of photocatalysts in diluted CO2 atmosphere. Herein, we designed and synthesized a series of dual metallosalen-based covalent organic frameworks (MM-Salen-COFs, M: Zn, Ni, Cu) for artificial photosynthetic diluted CO2 reduction and confirmed their advantage in comparison to that of single metal M-Salen-COFs. As a results, the ZnZn-Salen-COF with dual Zn sites exhibits a prominent visible-light-driven CO2-to-CO conversion rate of 150.9 µmol g-1 h-1 under pure CO2 atmosphere, which is ~6 times higher than that of single metal Zn-Salen-COF. Notably, the dual metal ZnZn-Salen-COF still displays efficient CO2 conversion activity of 102.1 µmol g-1 h-1 under diluted CO2 atmosphere from simulated flue gas conditions (15% CO2), which is a record high activity among COFs- and MOFs-based photocatalysts under the same reaction conditions. Further investigations and theoretical calculations suggest that the synergistic effect between the neighboring dual metal sites in the ZnZn-Salen-COF facilitates low concentration CO2 adsorption and activation, thereby lowering the energy barrier of the rate-determining step.

A finasteride patch for the treatment of androgenetic alopecia: A study of promoting permeability strategy using synthetic novel O-acylmenthols combined with ion-pair.

Currently, finasteride (FIN) is approved to treat androgenetic alopecia only orally, and the application of FIN in transdermal drug delivery system (TDDS) has introduced a new approach for treating the disease. This study was aimed to develop a FIN transdermal patch for the treatment of androgenetic alopecia（AGA） by combing ion-pair and O-acylmenthols (AM) as chemical permeation enhancers (CPEs). The formulation of patch was optimized though single-factor investigation and Box-Behnken design. The pharmacokinetics and androgenetic alopecia pharmacodynamics of the patch were evaluated. Additionally, the permeability enhancement mechanisms of ion-pair and AMs were explored at both the patch and skin levels. The effects of ion-pair and AMs on the patch were characterized by rheology study, FTIR, and molecular docking, and the effects on the skin were assessed through ATR-FTIR, Raman study, DSC, CLSM and molecular dynamics. The finalized formulation of FIN patches was consisted of 5 % (w/w) synthetic FIN-CA (Citric Acid), 6 % MT-C6 as CPEs, 25-AAOH as a pressure-sensitive adhesive (PSA), with a patch thickness of 80 ± 5 µm. The final Q24 h is 78.22 ± 5.18 µg/cm2. Based on the high FIN permeability, the pharmacokinetic analysis revealed that the FIN patch group exhibited a slower absorption rate (tmax = 7.3 ± 2.7 h), lower peak plasma concentration and slower metabolic rate (t1/2 = 6.2 ± 0.8 h, MRT0-t = 26.0 ± 7.8 h) compared to the oral group. Moreover, the FIN patch also demonstrated the same effect as the oral group in promoting hair growth in AGA mice. The results indicated that both FIN-CA and AMs could enhance the fluidity of the PSA and weaken the interaction between FIN-CA and PSA, thereby promoting the release of the FIN from the patch. The interaction sites on the skin for ion-pair and the four AMs were found in the stratum corneum (SC) of the skin, disrupting the tight arrangement of stratum corneum lipids. This study serves as a reference for the multi-pathway administration of FIN and the combination of ion-pair with AMs to enhance drug permeation.

Formation Mechanism and Prevention of Cu Undercut Defects in the Photoresist Stripping Process of MoNb/Cu Stacked Electrodes.

The Cu undercut is a recently discovered new defect generated in the wet stripping process of MoNb/Cu gate stacked electrodes for thin-film transistors (TFTs). The formation mechanism and preventive strategy of this defect were identified and investigated in this paper. The impact of stripper concentration and stripping times on the morphology and the corrosion potential (Ecorr) of Cu and MoNb were studied. It is observed that the undercut is Cu tip-deficient, not the theoretical MoNb indentation, and the undercut becomes severer with the increase in stripping times. The in-depth mechanism analysis revealed that the abnormal Cu undercut was not ascribed to the galvanic corrosion between MoNb and Cu but to the local crevice corrosion caused by the corrosive medium intruding along the MoNb/Cu interface. Based on this newly found knowledge, three possible prevention schemes (MoNiTi (abbreviated as Mo technology development (MTD) layer/Cu), MoNb/Cu/MTD, and MoNb/Cu/MoNb) were proposed. The experimental validation shows that the Cu undercut can only be completely eliminated in the MoNb/Cu/MTD triple-stacked structure with the top MTD layer as a sacrificial anode. This work provides an effective and economical method to avoid the Cu undercut defect. The obtained results can help ensure TFT yield and improve the performance of TFT devices.

Application of high-polarity hydroxyl polyacrylate pressure sensitive adhesive in rizatriptan transdermal drug delivery patch.

This study aimed to design a rizatriptan (RIZ) transdermal patch by combining of high-polarity hydroxyl pressure sensitive adhesive (PSA) AAOH-45 with an ion-pair strategy and investigate the molecular mechanism of high content hydroxyl PSA to enhance drug-PSA miscibility. RIZ free base, ion-pair complexes and PSAs containing hydroxyl group were prepared and characterized. Formulation factors including counter-ions, PSAs, drug-loading and others were optimized through single-factor studies and evaluated through pharmacokinetic studies and skin irritation tests. The properties of high polarity PSA and molecular mechanism of drug-PSA miscibility were investigated through molecular simulation, FTIR spectra, 13C NMR spectra, DSC, and rheology study. The optimized formulation contained 20 % (w/w) RIZ-OA (Rizatriptan-Oleic acid), 80 % AAOH-45 (w/w) as the matrix, and had a thickness of 90 µm. Compared with the oral group (MRT0-t = 5.96 ±â€¯0.97 h) and the control patch group (MRT0-t = 11.30 ±â€¯1.78 h), the pharmacokinetic behavior of the optimization group demonstrated sustained drug delivery behavior (MRT0-t = 20.21 ±â€¯0.61 h) with no irritation phenomenon. The miscibility of RIZ with PSAs was positively correlated with the mass percentage of 2-HEA. Higher polar similarity, lower flowability, and stronger intermolecular interaction were responsible for the higher compatibility of high hydroxyl PSA with the drug. This study provided a reference for increasing the drug-loading in PSA and developing RIZ patch.

Ferrimagnet-Based Neuromorphic Device Mimicking the Ventral Visual Pathway for High-Accuracy Target Recognition.

The ventral visual pathway (VVP) of the human brain efficiently implements target recognition by employing a deep hierarchical structure to build complex visual concepts from simple features. Artificial neural networks (ANNs) based on spintronic devices are capable of target recognition, but their poor interpretability and limited network depth hinder ANNs from mimicking the VVP. Hardware implementation of the VVP requires a biorealistic spintronic device as well as the corresponding interpretable and deep network structure, which have not been reported so far. Here, we report a ferrimagnetic neuron with a continuously differentiable exponential linear unit (CeLu) activation function, which is closer to biological neurons and could mitigate the issue of limited network depth. Meanwhile, we also demonstrate that a ferrimagnet can construct artificial synapses with high linearity and symmetry to meet the requirements of weight update algorithms. Based on these neurons and synapses, we propose an all-spin convolutional neural network (CNN) with a high interpretability and deep neural network, to mimic the VVP. Compared to the state-of-the-art spintronic-based neuromorphic computing model, the CNN with bionic function, using experimentally derived device parameters, achieves high recognition accuracies of over 91% and 98% on the CIFAR-10 datasets and the MNIST datasets, respectively, showing improvements of 1.13% and 1.76%. Our work provides a promising method to improve the bionic performance of spintronic device-based neural networks.

[Exploration and practice of constructing a case library for ideological and political education in immunology for graduate students].

Immunology is a foundational discipline in the fields of biology and medicine. For graduate students studying biology, medicine, pharmacy, biotechnology and related fields, immunology is a compulsory course. With the new requirements put forward by the Party and the country for higher education in the new era, integrating ideological and political education into the curriculum has become a new approach and focus in cultivating talents at universities. In recent years, our university has made progress and achievements in the reform of ideological and political education in graduate immunology teaching, completing the construction of a case library for ideological and political education. In the process of construction, we focused on professional knowledge and established the case library by systematically condensing ideological and political content into various categories. Through the use of case libraries, we have effectively solved the key problem of integrating professional knowledge and ideological and political education into graduate immunology teaching, providing strong support for teachers, improving the teaching effectiveness of professional courses, and assisting in achieving the teaching goal of "Cultivate morality for humanity, nurture talents for combat".

[Research progress of mesenchymal stem cells in osteoimmunity].

Mesenchymal stem cells (MSCs) have the potential for proliferation, multidirectional differentiation and immune regulation. At present, MSCs have been found and isolated from a variety of tissues. Because of their biological characteristics of proliferation, migration and differentiation in vitro, they can be cultured and induced to obtain biologically active cells and their products. More importantly, MSCs also have immunomodulatory functions and play an important role in the treatment of bone injury-related diseases by stem cell transplantation. Therefore, from the perspective of biological characteristics and related functions of MSCs, this article discusses the role of MSCs in osteoimmunity and the mechanism of treatment of bone injury diseases, which will help to fully understand the function of MSCs in physiological and pathological states.

Innovative Long-Acting Bisoprolol Patch: Synergistic Ion-Pair Skin Adsorption for Drug Delivery Control Coupled with Dynamic Modulation of Penetration Enhancers.

This study aims to develop a sustained release patch for bisoprolol (BSP) to address the issue of blood pressure fluctuations caused by traditional dosing methods, ensuring continuous drug release and efficient utilization. Long-chain saturated fatty acids (C6-C12) were chosen as counterions to precisely control BSP's permeation rate in the patch formulation, and the ion-pairing strategy's mechanism in drug delivery was thoroughly investigated. Molecular docking results revealed significant differences in the adsorption capacities of different ion pairs in the stratum corneum (SC) and epidermis, directly influencing their residence times and thereby regulating BSP's passive diffusion rate. Particularly, the BSP-C10 ion pair successfully reduced BSP's permeation rate to one-third of its baseline. To enhance drug delivery efficiency and reduce costs, chemical permeation enhancers (CPEs) are typically added to sustained release patches. In contrast to traditional static analyses based on cumulative permeation, this study utilized ATR-FTIR dynamic detection of isopropyl myristate (IPM) as a preferred enhancer, studying its disruptive effects on the skin barrier during drug delivery. The study observed that during drug delivery, the interaction between IPM and skin lipids follows a U-shaped trend: initially increasing, then decreasing, with the peak occurring at 10 h. Similarly, the drug delivery rate displays a comparable pattern. The addition of IPM as CPE increased the patch utilization rate from 39.8 ± 4.31 to 79.8 ± 7.27%. This strategy aims to rapidly reduce blood pressure in the initial phase with subsequent weakening of IPM disruption, allowing the ion-pairing strategy to dominate drug delivery control and maintain stable long-term therapeutic effects. Pharmacokinetic studies demonstrated that the newly developed BSP sustained release patch maintains stable blood drug concentrations, reduces burst release effects, increases bioavailability to 84.679%, doubles MRT0-t, halves Cmax, and significantly reduces the occurrence of blood pressure fluctuations.

Combining ion-pair strategy and percutaneous permeation enhancers to develop sustained-release paliperidone patch.

In this study, a sustained-release paliperidone (PAL) patch was developed using a combination of ion-pair strategy and percutaneous permeation enhancers (PPEs). The ion-pair strategy was used to improve drug-adhesive miscibility and control drug release. PPEs were used to break SC barrier function to facilitate drug skin permeation. The in vitro skin permeation experiments using single-factor experiments and Box-Behnken design gave the optimized formulation, a 55 µm adhesive thickness patch with 7 % (w/w) PAL-LA (Lauric acid), 9.7 % (w/w) Plurol® Oleique CC 497 (POCC). Moreover, the pharmacokinetic study confirmed its potential in sustained-release transdermal patch with longer MRT0-t (18.35 ± 3.11 h) and higher BA (63.14 %) than the gavage group (Cmax = 6.64 ± 2.61 µg/mL, MRT0-t = 2.88 ± 1.06 h, BA = 45.70 %) without significant increasing Cmax. The mechanism study revealed that forming ion-pairs effectively modulated drug's physicochemical properties and doubly ionic H-bond strength to improve drug miscibility in patches. To summarize, a sustained-release patch of PAL was successfully developed, which provided a strategy for sustained-release patches with good drug-polymer miscibility, drug controlled-release, and feasible drug utilization features.

Arbitrarily Configurable Nonlinear Topological Modes.

Topological modes (TMs) are typically localized at boundaries, interfaces and dislocations, and exponentially decay into the bulk of a large enough lattice. Recently, the non-Hermitian skin effect has been leveraged to delocalize the wave functions of TMs from the boundary and thus to increase the capacity of TMs dramatically. Here, we explore the capability of nonlinearity in designing and configuring the wave functions of TMs. With growing intensity, wave functions of these in-gap nonlinear TMs undergo an initial deviation from exponential decay, gradually merge into arbitrarily designable plateaus, then encompass the entire nonlinear domain, and eventually concentrate at the nonlinear boundary. Intriguingly, such extended nonlinear TMs are still robust against defects and disorders, and stable in dynamics under external excitation. Advancing the conceptual understanding of the nonlinear TMs, our results open new avenues for increasing the capacity of TMs and developing compact and configurable topological devices.

Dual modules-molecularly imprinted patch-enabled enantioselectively controlled release of racemic drugs for transdermal delivery.

Over 90 % of chiral drugs applied in transdermal drug delivery system (TDDS) are racemates, significantly increasing risks of side effects. Herein, we designed a chiral molecularly imprinted patch (CMIP) that achieved enantioselectively controlled release of S-enantiomers (eutomers) and inhibited the release of R-enantiomers (distomers) for transdermal drug delivery. It is composed of chiral pressure sensitive adhesive (PSA) and molecularly imprinted polymers (MIP), showing better transdermal delivery of S-enantiomers than that of R-enantiomers in vitro (1.86-fold) and in vivo (3.74-fold), significantly decreasing the intake of distomers. Additionally, synthesized fluorescent probe enantiomers visualized enantioselective process of CMIP. Furthermore, investigations of molecular mechanism indicated that dependence on spatial conformation was dominant. On one hand, imprinted cavity of MIP with D-isomer and stronger chiral interaction with R-enantiomers led to more specific adsorption. On the other hand, L-isomer of PSA controlled the release of S-enantiomers by multiple interaction including chiral H-bond, π-π interaction and Van der Waals force. Tthus, the innovatively designed transdermal patch with enantioselective ability released eutomers of racemate and simultaneously inhibited release of distomers, significantly improving therapeutical efficiency and avoiding overdose.

Development of levamlodipine long-acting patches based on an ion-pair strategy: Investigation of the mechanism for reducing skin irritation.

The aim of this study was to develop a long-acting transdermal patch of levamlodipine (LAM) using an ion-pair strategy to reduce the skin irritation induced by topical application of LAM and explore the mechanism underlying the improvement of skin irritation. The formulation was optimized through porcine in vitro transdermal experiments and rabbit in vivo skin irritation tests. The obtained formulation consisted of poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl) acrylamide) (PENH) as the adhesive matrix, 13.00 % levamlodipine-sorbic acid ion-pair complex (LAM-SA) (w/w), and 10 % isopropyl myristate (IPM) (w/w), with a patch thickness of 70 µm, achieving an erythema index of 188 for rabbit skin and 117-187 for human skin (264 for rabbit skin and 110-260 for human skin in the absence of sorbic acid (SA)). In vivo rabbit and human skin erythema analysis and H&E staining verified that the optimized ion-pair patch effectively reduced skin irritation. Drug distribution experiments in the skin, ATR-FTIR, and molecular simulation were used to characterize the mechanism by which the ion-pair reduced skin irritation. Excessive accumulation of LAM in the epidermis induced secondary structural changes in keratin, resulting in skin barrier damage and inflammatory response. The formation of the LAM-SA ion pair altered physicochemical properties of LAM, reducing drug retention in the epidermis and, thereby, reducing skin irritation. This study demonstrated the potential of the ion-pair strategy to improve the safety of transdermal drug delivery system (TDDS) and provided a means for reducing skin irritation caused by the active pharmaceutical ingredient (API) itself.

Advancing Chlorophyll Photostability: Dual Physicochemical Protection via Ce-Doped Hydrotalcite Organic-Inorganic Hybrid Pigments.

In pursuit of enhancing the photostability of chlorophyll, a novel organic-inorganic hybrid pigment has been synthesized via a supramolecular intercalation assembly method, incorporating cerium-ion-doped hydrotalcite as the host matrix and chlorophyll as the intercalated guest molecule. This innovative pigment amalgamates the vivid coloration properties of organic dyes with the robust stability characteristic of inorganic substances. Determined from the detailed investigation of the structural evolution of chlorophyll during photodegradation, the dual physicochemical protection mechanism is critical to the advancement of chlorophyll photostability. It leverages the oxygen barrier attributes of the hydrotalcite's laminate structure and the ultraviolet light absorption and scattering capabilities of CeO2 nanoparticles formed in situ. Furthermore, Ce-doping introduces a redox cycle between Ce4+ and Ce3+ ions, which serves as a chemical defense by neutralizing reactive oxygen species that emerge during chlorophyll degradation. This multifaceted approach results in a substantial enhancement of photostability, with the hybrid pigment containing 0.3 Ce doped content, demonstrating a mere 5.90% alteration in reflectance at the 635 nm peak after 250 h of UV-accelerated aging. This breakthrough provides a dual physicochemical protective strategy that not only significantly prolongs the lifespan of chlorophyll pigments but also holds potential for broadening their application scope in various industries, including plastics and coatings, where color fastness and durability are paramount.

Changes in the Antimicrobial Resistance and Bacterial Epidemiology of Moraxella catarrhalis from Pediatric Community-Acquired Pneumonia Patients During the COVID-19 Pandemic: A 5-Year Study at a Tertiary Hospital of Southwest China.

This study aimed to assess the impact of the COVID-19 pandemic on Moraxella catarrhalis infections in pediatric patients hospitalized with community-acquired pneumonia (CAP). The epidemiological features and antimicrobial resistance (AMR) patterns of M. catarrhalis were compared between the pre-pandemic period (2018-2019) and during the pandemic (2020-2022). The results revealed a marked increase in the positivity rate of M. catarrhalis in 2020 and 2021 compared with the pre-pandemic years. The median age of the patients increased significantly in 2021 and 2022, while the proportion of male patients decreased substantially from 2019 to 2021. In addition, there were notable changes in the co-infections of Haemophilus influenzae, parainfluenza virus, and respiratory syncytial virus during the COVID-19 pandemic. The AMR profile of M. catarrhalis also changed significantly, showing increased resistance to ampicillin, but decreased resistance to trimethoprim-sulfamethoxazole and ofloxacin, and a lower proportion of multidrug-resistant isolates. Notably, ampicillin resistance increased among ß-lactamase-producing isolates. Before the pandemic, the number and detection rate of isolates, along with resistance to ampicillin and trimethoprim-sulfamethoxazole, were seasonally distributed, peaking in autumn and winter. However, coinciding with local COVID-19 outbreaks, these indices sharply fell in February 2020, and the number of isolates did not recover during the autumn and winter of 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection landscape of M. catarrhalis in pediatric CAP patients, as evidenced by shifts in the detection rate, demographic characteristics, respiratory co-infections, AMR profiles, and seasonal patterns.

Vascular restoration through local delivery of angiogenic factors stimulates bone regeneration in critical size defects.

Critical size bone defects represent a significant challenge worldwide, often leading to persistent pain and physical disability that profoundly impact patients' quality of life and mental well-being. To address the intricate and complex repair processes involved in these defects, we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue. Specifically, we observed a decrease in progenitor lineage cells and endothelial cells, coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue. Furthermore, our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects, notably influenced by reduction of Spp1 and Cxcl12 expression. This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells, underscoring its significance in the regeneration process. In response to these findings, we developed an innovative approach to enhance bone regeneration in critical size bone defects. Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12. This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo. To evaluate the efficacy of our approach, we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects. Our results demonstrated restored angiogenesis, accelerated bone regeneration, alleviated pain responses and improved mobility in treated mice.

Effect of alternative fuels on the emissions of a passenger car under real-world driving conditions: a comparison of biodiesel, gas-to-liquid, coal to liquid.

Fossil fuel energy crisis and environmental pollution have initiated the scientific research on alternative fuels. Biodiesel (B100), gas to liquid (G100), and coal to liquid (C100) are superb selections to be substitutes for conventional diesel. To better investigate the emission characteristics of the alternative fuels mentioned above, a portable emission measurement system (PEMS) was used to carry out this study under real-world driving conditions. Results showed that the driving conditions had a notable effect on the vehicle emissions, the CO, THC, and CO2 emissions were higher under urban condition, and the NOx, PM (particle mass), and PN (particle number) emissions were higher under suburban condition. The expressway condition resulted in lower emissions except for PN due to more nucleation particles emitted. The use of B100, G100, and C100 fuels led to a reduction of more than 50% in the CO emission, especially for the C100, but the reduction effects for the THC were not obvious, and among them, G100 is the most prominent. Higher NOx emission was emitted after using the three fuels, especially for the B100; meanwhile, B100 increased the CO2, but G100 and C100 decreased the CO2 emission compared with D100. The PN emissions reduced by 1-2 orders of magnitude in comparison with those from D100 after using the three alternative fuels, and more than 50% of the PM could be reduced. B100 has the most significant particle reduction effect due to its oxygen-containing property, and it produced an evidently higher proportion of nucleation particles than D100, followed by G100 and C100.