In vitro-irradiated cancer vaccine enhances anti-tumor efficacy of radiotherapy and PD-L1 blockade in a syngeneic murine breast cancer model.

BACKGROUND AND PURPOSE: Local radiotherapy (RT) exerts immunostimulatory effects by inducing immunogenic cell death. However, it remains unknown whether in vitro-irradiated tumor cells can elicit anti-tumor responses and enhance the efficacy of local RT and immune checkpoint inhibitors when injected in vivo. METHODS AND MATERIALS: We tested the "in vitro-irradiated cancer vaccine (ICV)", wherein tumor cells killed by varying doses of irradiation and their supernatants are intravenously injected. We examined the efficacy of combining local RT (24 Gy in three fractions), PD-L1 blockade, and the ICV in a murine breast cancer model. The immune cell profiles were analyzed via flow cytometry and immunohistochemistry. The cytokine levels were measured by multiplex immunoassays. RESULTS: The ICV significantly increased the effector memory phenotype and interferon-γ production capacity in splenic CD8+ T cells. The in vitro-irradiated products contained immune response-related molecules. When combined with local RT and PD-L1 blockade, the ICV significantly delayed the growth of irradiated and non-irradiated tumors. The triple combination therapy increased the proportions of CD8+ T cells and effector memory CD8+ T cells while decreasing the proportion of CTLA-4+ exhausted CD8+ T cells within tumor microenvironment. Additionally, plasma level of interferon-γ and proliferation of effector T cells in the spleen and tumor-draining lymph nodes were significantly increased by the triple combination therapy. CONCLUSIONS: The ICV enhanced the therapeutic efficacy of local RT and PD-L1 blockade by augmenting anti-tumor immune responses. Our findings suggest a therapeutic potential of in vitro-irradiation products of tumor cells.

Calcined pyrite accelerates sulfur metabolic and electron transfer in driving targeted microbial fuel cell denitrification.

The sulfur powder as electron donor in driving dual-chamber microbial fuel cell denitrification (S) process has the advantages in economy and pollution-free to treat nitrate-contained groundwater. However, the low efficiency of electron utilization in sulfur oxidation (ACE) is the bottleneck to this method. In this study, the addition of calcined pyrite to the S system (SCP) accelerated electron generation and intra/extracellular transfer efficiency, thereby improving ACE and denitrification performance. The highest nitrate removal rate reached to 3.55 ± 0.01 mg N/L/h in SCP system, and the ACE was 103 % higher than that in S system. More importantly, calcined pyrite enhanced the enrichment of functional bacteria (Burkholderiales, Thiomonas and Sulfurovum) and functional genes which related to sulfur metabolism and electron transfer. This study was more effective in removing nitrate from groundwater without compromising the water quality.

Wide-Range Excitation-Dependent Phosphorescence of Coordination Polymers Exhibiting Dynamic Anticounterfeiting, White-Light Emission, and Antibacterial Performance.

Multicolor-tunable room-temperature phosphorescence (RTP) is attracting wide attention in optoelectronic applications. Here, we propose a coordination-oriented assembly approach to achieve wide-range RTP with a benzimidazole derivative (2,7-diazabenzimidazole, DZBIM) as a luminogen. These two compounds exhibit unexpected excitation-responsive RTP emission, and the phosphorescence emission nearly covers the entire visible region with the change of the excitation wavelength from 360 to 620 nm. To the best of our knowledge, this is the first report of coordination polymers with such a full-color-tunable RTP. Compound 1 also shows white-light emission upon excitation at 280 nm. Experimental and theoretical results demonstrate that multiple intermolecular interactions and emission centers from different aggregates are responsible for the generation of multicolor emission. The white-light emission and multiple anticounterfeiting are explored. Besides, compound 1 exhibits high antibacterial activity benefiting from efficient 1O2 generation. This work provides an efficient way to prepare a color-tunable RTP.

Projection superimposition for the generation of high-resolution digital grating.

Fringe projection profilometry based on MEMS micro-vibration mirrors is very promising due to its rapid projection, large depth of field, compact size, and low cost. Although high-frequency fringes can achieve accurate reconstruction, the projector must offer sufficient pixel resolution. In this paper, we proposed a high-resolution projection technique called the delay superposition method. During a single exposure time of the camera, the projector projects a group of low-resolution fringe patterns, which are delayed according to the movement characteristics of the vibration mirror. Then, the camera exposure superimposes these low-resolution images to form a high-resolution image. These two steps effectively subdivide the angle intervals, thereby achieving a pixel interpolation. Finally, experimental results show that the proposed method can significantly improve the projector's pixel resolution and reconstruction accuracy. The proposed method allows the MEMS projector's pixel resolution (along one direction) to far exceed that of common DLP projectors. It holds great application potential for high-frequency fringe projection.

A simulated microgravity-oriented AIE probe-ECM hydrogel-integrated chip for cell culture and superoxide anion radical detection.

Human space activities have been continuously increasing. Astronauts experiencing spaceflight are faced with health problems caused by special space environments such as microgravity, and the investigation of cell injury is fundamental. The development of a platform capable of cell culture and injury detection is the prerequisite for the investigation. Constructing a platform suitable for special conditions in space life science research is the key issue. The ground-based investigation is an indispensable part of the research. Accordingly, a simulated microgravity (SMG)-oriented integrated chip platform capable of 3D cell culture and in situ visual detection of superoxide anion radical (O2•-) is developed. SMG can cause oxidative stress in human cells, and O2•- is one of the signaling molecules. Thus, a O2•--responsive aggregation-induced emission (AIE) probe is designed, which shows high selectivity and sensitivity to O2•-. Moreover, the probe exhibits abilities of long-term and wash-free staining to cells due to the AIE behavior, which is precious for space cell imaging. Meanwhile, a chip with a high-aspect-ratio chamber for adequate medium storage for the lack of the perfusion system during the SMG experiment and a cell culture chamber which can integrate the extracellular matrix (ECM) hydrogel for the bioinspired 3D cell culture is fabricated. In addition, a porous membrane is introduced between the chambers to prevent the hydrogel from separating during the SMG experiment. The afforded AIE probe-ECM hydrogel-integrated chip can achieve 3D culturing of U87-MG cells and in situ fluorescent detection of endogenous O2•- in the cells after long-term staining under SMG. The chip provides a powerful and potential platform for ground-based investigation in space life science and biomedical research.

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

Hepatitis B Reactivation and Vaccination Effectiveness after Solid Organ Transplantation: A Matched Case-Control Study.

Solid organ transplant (SOT) recipients are at significant risk of hepatitis B (HB) virus (HBV) reactivation (HBVr). Despite the clinical significance of HBVr after solid organ transplantation, data on the risk factors for HBVr and vaccine effectiveness in SOT recipients with resolved HBV infection are limited. This study evaluated the risk factors for HBVr and the seroconversion rates after HBV vaccination in SOT recipients. Patients who had undergone solid organ transplantation and those with a resolved HBV infection were identified. We matched patients who experienced post-transplantation HBVr with those who did not. We also explored the characteristics and seroconversion rates of HBV-vaccinated patients following transplantation. In total, 1299 SOT recipients were identified as having a resolved HBV infection at the time of transplantation. Thirty-nine patients experienced HBVr. Pre-transplant HB surface antibodies (anti-HBs) positivity and allograft rejection within 3 months after transplantation were independently associated with HBVr. Among the 17 HBV-vaccinated patients, 14 (82.4%) received three or fewer vaccine doses, and 13 (76.5%) had seroconversion with positive anti-HBs results. Pre-transplant anti-HBs(-) status and allograft rejection were risk factors for HBVr in SOT recipients with a resolved HBV infection, and HBV vaccination after transplantation resulted in a high rate of anti-HBs seroconversion. HBV vaccination after transplantation should be considered to reduce the HBVr risk.

Development of boronic acid catalysts for direct amidation of aromatic carboxylic acids using fluorescence-based screening.

Direct amidation of carboxylic acids with amines holds significant importance; therefore, catalytic processes involving boronic acids have undergone extensive investigation. However, studies focused on the amidation of aromatic carboxylic acids remain limited. In this study, we introduce a fluorescence-based screening methodology employing an anthracene derivative probe, facilitating the rapid evaluation of various amidation catalysts. Using this approach, boronic acids were evaluated for their catalytic potential. Our findings reveal that 2-hydroxyphenylboronic acid (C7), previously deemed inefficient for aliphatic acids, effectively catalyzes the amidation of aromatic acids. The catalysts identified through this method consistently achieved high yields, reaching up to 98% across a broad spectrum of substrates.

Field Collection and Laboratory Maintenance of Canopy-Forming Giant Kelp to Facilitate Restoration.

Canopy-forming kelps are essential foundation species, supporting biodiversity and providing ecosystem services valued at more than USD$500 billion annually. The global decline of giant kelp forests due to climate-driven ecological stressors underscores the need for innovative restoration strategies. An emerging restoration technique known as 'green gravel' aims to seed young kelps over large areas without extensive underwater labor and represents a promising restoration tool due to cost-effectiveness and scalability. This video article illustrates a protocol and tools for culturing giant kelp, Macrocystis pyrifera. It also provides a resource for further studies to address the successes and limitations of this method in field settings. We outline field and laboratory-based methods for collecting reproductive tissue, sporulating, inoculating, rearing, maintaining, and monitoring substrates seeded with early life stages using the 'green gravel' technique. The protocol simplifies and centralizes current restoration practices in this field to support researchers, managers, and stakeholders in meeting kelp conservation objectives.

Multiple independent origins of the female W chromosome in moths and butterflies.

Lepidoptera, the most diverse group of insects, exhibit female heterogamy (Z0 or ZW), which is different from most other insects (male heterogamy, XY). Previous studies suggest a single origin of the Z chromosome. However, the origin of the lepidopteran W chromosome remains poorly understood. Here, we assemble the genome from females down to the chromosome level of a model insect (Bombyx mori) and identify a W chromosome of approximately 10.1 megabase using a newly developed tool. In addition, we identify 3593 genes that were not previously annotated in the genomes of B. mori. Comparisons of 21 lepidopteran species (including 17 ZW and four Z0 systems) and three trichopteran species (Z0 system) reveal that the formation of Ditrysia W involves multiple mechanisms, including previously proposed canonical and noncanonical models, as well as a newly proposed mechanism called single-Z turnover. We conclude that there are multiple independent origins of the W chromosome in the Ditrysia (most moths and all butterflies) of Lepidoptera.

Inhibition of zinc ions in sulfur-driven autotrophic denitrification process: What is the behavior of extracellular polymeric substances?

Sulfur-driven autotrophic denitrification (SAD) process is a cost-effective and sustainable method for nitrogen removal from wastewater. However, a higher concentration of zinc ions (Zn(II)) flowing into wastewater treatment plants poses a potential threat to the SAD process. This study examined that a half maximal inhibitory concentration (IC50) of Zn(II) was 7 mg·L-1 in the SAD process. Additionally, the addition of 20 mg·L-1 Zn(II) resulted in a severe accumulation of nitrite to 150.20 ± 6.00 mg·L-1 when the initial concentration of nitrate was 500 mg·L-1. Moreover, the activities of nitrate reductase, nitrite reductase, dehydrogenase and electron transport system were significantly inhibited under Zn(II) stress. The addition of Zn(II) inhibited EPS secretion and worsened electrochemical properties. The result was attributed to the spontaneous binding between EPS and Zn(II), with a ΔG of -17.50 KJ·mol-1 and a binding constant of 1.77 × 104 M-1, respectively. Meanwhile, the protein, fulvic acid, and humic-like substances occurred static quenching after Zn(II) addition, with -OH and -C=O groups providing binding sites. The binding sequence was fulvic acid→protein→humic acid and -OH â†’ -C=O. Zn(II) also reduced the content of α-helix, which was unfavorable for electron transfer. Additionally, the Zn(II) loosened protein structure, resulting in a 50 % decrease in α-helix/(ß-sheet+random coil). This study reveals the effect of Zn(II) on the SAD process and enhances our understanding of EPS behavior under metal ions stress.

Development of a prediction model for cognitive impairment of sarcopenia using multimodal neuroimaging in non-demented older adults.

INTRODUCTION: Despite prior research on the association between sarcopenia and cognitive impairment in the elderly, a comprehensive model that integrates various brain pathologies is still lacking. METHODS: We used data from 528 non-demented older adults with or without sarcopenia in the Catholic Aging Brain Imaging (CABI) database, containing magnetic resonance imaging scans, positron emission tomography scans, and clinical data. We also measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five times sit-to-stand test (5STS). RESULTS: All components of sarcopenia were significantly correlated with global cognitive function, but cortical thickness and amyloid-beta (Aß) retention had distinctive relationships with each measure. In the path model, brain atrophy resulting in cognitive impairment was mediated by Aß retention for SMI and periventricular white matter hyperintensity for HGS, but directly affected by the 5STS. DISCUSSION: Treatments targeting each sub-domain of sarcopenia should be considered to prevent cognitive decline. HIGHLIGHTS: We identified distinct impacts of three sarcopenia measures on brain structure and Aß. Muscle mass is mainly associated with Aß and has an influence on the brain atrophy. Muscle strength linked with periventricular WMH and brain atrophy. Muscle function associated with cortical thinning in specific brain regions. Interventions on sarcopenia may be important to ease cognitive decline in the elderly.

Automatic detection of the third molar and mandibular canal on panoramic radiographs based on deep learning.

PURPOSE: This study aims to develop a deep learning framework for the automatic detection of the position relationship between the mandibular third molar (M3) and the mandibular canal (MC) on panoramic radiographs (PRs), to assist doctors in assessing and planning appropriate surgical interventions. METHODS: Datasets D1 and D2 were obtained by collecting 253 PRs from a hospitals and 197 PRs from online platforms. The RPIFormer model proposed in this study was trained and validated on D1 to create a segmentation model. The CycleGAN model was trained and validated on both D1 and D2 to develop an image enhancement model. Ultimately, the segmentation and enhancement models were integrated with an object detection model to create a fully automated framework for M3 and MC detection in PRs. Experimental evaluation included calculating Dice coefficient, IoU, Recall, and Precision during the process. RESULTS: The RPIFormer model proposed in this study achieved an average Dice coefficient of 92.56 % for segmenting M3 and MC, representing a 3.06 % improvement over the previous best study. The deep learning framework developed in this research enables automatic detection of M3 and MC in PRs without manual cropping, demonstrating superior detection accuracy and generalization capability. CONCLUSION: The framework developed in this study can be applied to PRs captured in different hospitals without the need for model fine-tuning. This feature is significant for aiding doctors in accurately assessing the spatial relationship between M3 and MC, thereby determining the optimal treatment plan to ensure patients' oral health and surgical safety.

Radiomics-based hybrid model for predicting radiation pneumonitis: A systematic review and meta-analysis.

PURPOSE: This study reviewed and meta-analyzed evidence on radiomics-based hybrid models for predicting radiation pneumonitis (RP). These models are crucial for improving thoracic radiotherapy plans and mitigating RP, a common complication of thoracic radiotherapy. We examined and compared the RP prediction models developed in these studies with the radiomics features employed in RP models. METHODS: We systematically searched Google Scholar, Embase, PubMed, and MEDLINE for studies published up to April 19, 2024. Sixteen studies met the inclusion criteria. We compared the RP prediction models developed in these studies and the radiomics features employed. RESULTS: Radiomics, as a single-factor evaluation, achieved an area under the receiver operating characteristic curve (AUROC) of 0.73, accuracy of 0.69, sensitivity of 0.64, and specificity of 0.74. Dosiomics achieved an AUROC of 0.70. Clinical and dosimetric factors showed lower performance, with AUROCs of 0.59 and 0.58. Combining clinical and radiomic factors yielded an AUROC of 0.78, while combining dosiomic and radiomics factors produced an AUROC of 0.81. Triple combinations, including clinical, dosimetric, and radiomics factors, achieved an AUROC of 0.81. The study identifies key radiomics features, such as the Gray Level Co-occurrence Matrix (GLCM) and Gray Level Size Zone Matrix (GLSZM), which enhance the predictive accuracy of RP models. CONCLUSIONS: Radiomics-based hybrid models are highly effective in predicting RP. These models, combining traditional predictive factors with radiomic features, particularly GLCM and GLSZM, offer a clinically feasible approach for identifying patients at higher RP risk. This approach enhances clinical outcomes and improves patient quality of life. PROTOCOL REGISTRATION: The protocol of this study was registered on PROSPERO (CRD42023426565).

Gelatin methacryloyl microneedle loaded with 3D-MSC-Exosomes for the protection of ischemia-reperfusion.

Exosomes (Exo) generated from mesenchymal stem cells (MSCs) have great therapeutic potential in ischemia-reperfusion treatment. For best therapeutic effect, high quality Exo product and effective delivery system are indispensable. In this study, we developed a new strategy for ischemia-reperfusion recovery by combining MSCs 3D (3D-MSC) culturing technology to generate Exo (3D-MSC-Exo) and microneedle for topical delivery. Firstly, primary MSCs from neonatal mice were isolated and 3D cultured with gelatin methacryloyl (GelMA) hydrogel to prepare 3D-MSC-Exo. The 3D-MSC showed better viability and 3D-MSC-Exo exhibited more effective effects of reducing neuroinflammation, inhibiting glial scarring, and promoting angiogenesis. Subsequently, the biocompatible GelMA was used to construct microneedles for 3D-Exo delivery (GelMA-MN@3D-Exo). The results demonstrated GelMA microneedles had excellent 3D-Exo loading capacity and enabled continuous 3D-Exo release to maintain effective therapeutic concentrations. Furthermore, the rat middle cerebral artery occlusion (MCAO) model was established to evaluate the therapeutic effect of GelMA-MN@3D-Exo in ischemia-reperfusion in vivo. Animal experiments showed that the GelMA-MN@3D-Exo system could effectively reduce the local neuroinflammatory reaction, promote angiogenesis and minimize glial scar proliferation in ischemia-reperfusion. The underlying reasons for the stronger neuroprotective effect of 3D-Exo was further studied using mass spectrometry and transcriptome assays, verifying their effects on immune regulation and cell proliferation. Taken together, our findings demonstrated that GelMA-MN@3D-Exo microneedle can effectively attenuate ischemia-reperfusion cell damage in the MCAO model, which provides a promising therapeutic strategy for ischemia-reperfusion recovery.

Electromagnetic Cellularized Patch with Wirelessly Electrical Stimulation for Promoting Neuronal Differentiation and Spinal Cord Injury Repair.

Although stem cell therapy holds promise for the treatment of spinal cord injury (SCI), its practical applications are limited by the low degree of neural differentiation. Electrical stimulation is one of the most effective ways to promote the differentiation of stem cells into neurons, but conventional wired electrical stimulation may cause secondary injuries, inflammation, pain, and infection. Here, based on the high conductivity of graphite and the electromagnetic induction effect, graphite nanosheets with neural stem cells (NSCs) are proposed as an electromagnetic cellularized patch to generate in situ wirelessly pulsed electric signals under a rotating magnetic field for regulating neuronal differentiation of NSCs to treat SCI. The strength and frequency of the induced voltage can be controlled by adjusting the rotation speed of the magnetic field. The generated pulsed electrical signals promote the differentiation of NSCs into functional mature neurons and increase the proportion of neurons from 12.5% to 33.7%. When implanted in the subarachnoid region of the injured spinal cord, the electromagnetic cellularized patch improves the behavioral performance of the hind limbs and the repair of spinal cord tissue in SCI mice. This work opens a new avenue for remote treatment of SCI and other nervous system diseases.

Dosimetric analysis of six whole-breast irradiation techniques in supine and prone positions.

In breast cancer radiation therapy, minimizing radiation-related risks and toxicity is vital for improving life expectancy. Tailoring radiotherapy techniques and treatment positions can reduce radiation doses to normal organs and mitigate treatment-related toxicity. This study entailed a dosimetric comparison of six different external beam whole-breast irradiation techniques in both supine and prone positions. We selected fourteen breast cancer patients, generating six treatment plans in both positions per patient. We assessed target coverage and organs at risk (OAR) doses to evaluate the impact of treatment techniques and positions. Excess absolute risk was calculated to estimate potential secondary cancer risk in the contralateral breast, ipsilateral lung, and contralateral lung. Additionally, we analyzed the distance between the target volume and OARs (heart and ipsilateral lung) while considering the treatment position. The results indicate that prone positioning lowers lung exposure in X-ray radiotherapy. However, particle beam therapies (PBTs) significantly reduce the dose to the heart and ipsilateral lung regardless of the patient's position. Notably, negligible differences were observed between arc-delivery and static-delivery PBTs in terms of target conformity and OAR sparing. This study provides critical dosimetric evidence to facilitate informed decision-making regarding treatment techniques and positions.

Construction of injectable micron-sized polymorphic vesicles for prolonged local anesthesia with weekly sustained release of ropivacaine.

Currently, to overcome the short half-life of the local anesthetic ropivacaine, drug delivery systems such as nanoparticles and liposomes have been used to prolong the analgesic effect, but they are prone to abrupt release from the site of administration or have poor slow-release effects, which increases the risk of cardiotoxicity. In this study, injectable lipid suspensions based on ropivacaine-docusate sodium hydrophobic ion pairing (HIP) were designed to significantly prolong the duration of analgesia. The resulting ion-paired lipid suspension (HIP/LIPO) had a micrometer scale and a high zeta potential, which facilitates stable in situ retention. The strong interaction between docusate sodium and ropivacaine was verified using thermal and spectroscopic analyses, and the formation of micron-sized polymorphic vesicles was attributed to the mutual stabilizing interactions between ropivacaine-docusate sodium HIP, docusate sodium and lecithin. The HIP/LIPO delivery system could maintain drug release for more than 5 days in vitro and achieve high analgesic efficacy for more than 10 days in vivo, reducing the side effects associated with high drug doses. The stable HIP/LIPO delivery system is a promising strategy that offers a clinically beneficial alternative for postoperative pain management and other diseases.