Surgery, chemoradiotherapy, or chemoradiation plus immunotherapy: Treatment strategies for nonmetastatic anal squamous cell carcinoma.

The current standard of care for anal squamous cell carcinoma (ASCC) is definitive concurrent chemoradiotherapy (CRT). However, about a third of patients may experience treatment failure. Recently, immunotherapy has emerged as a novel strategy for metastatic ASCC patients. We evaluated the efficacy and safety of surgery, CRT alone, and CRT with immunotherapy (CRT-I) in 100 nonmetastatic ASCC patients, treated from April 2012 through May 2023, by determining survival outcomes and acute adverse events. The median (range) follow-up was 30.7 (7.6 to 134.9) months. The study cohort 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were 80.7 %, 62.2 %, 71.1 %, and 67.6 %, respectively. The Surgery group had significantly lower rates than the CRT and CRT-I groups for 3-year PFS (33.1% vs. 65.2% vs. 92.9 %, P < 0.001), DMFS (46.7% vs. 74.6% vs. 92.9 %, P = 0.002) and LRFS (37.0% vs. 73.3% vs. 92.9 %, P < 0.001), respectively. All patients receiving CRT-I were alive at last follow-up. Of 100 patients, 26 (26.0 %) experienced severe (≥ grade 3) acute toxicity. Of 24 patients receiving CRT-I, 8 (33.3 %) had severe acute toxicity. Using immunohistochemistry, peritumoural stromal infiltration by CD8+ T cells was significantly higher after CRT-I compared to before CRT-I and to after CRT alone. The addition of immunotherapy to CRT may be an effective first-line treatment option with favourable survival outcomes and acceptable toxicity for patients with ASCC. A prospective, randomized trial assessing the efficacy of CRT combined with a PD-1 inhibitor in patients with locally advanced ASCC is in progress.

Myelin oligodendrocyte glycoprotein-associated transverse myelitis after SARS-CoV-2 infection: A case report.

BACKGROUND: Cases of myelin oligodendrocyte glycoprotein (MOG) antibody-related disease have a history of coronavirus disease 2019 infection or its vaccination before disease onset. Severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection has been considered to be a trigger of central nervous system autoimmune diseases. CASE SUMMARY: Here we report a 20-year male with MOG-associated transverse myelitis after a SARS-CoV-2 infection. The patient received a near-complete recovery after standard immunological treatments. CONCLUSION: Attention should be paid to the evaluation of typical or atypical neurological symptoms that may be triggered by SARS-CoV-2 infection.

Feasibility and Effectiveness of Venoarterial Extracorporeal Membrane Oxygenation Plus Intra-Aortic Balloon Pump Assisted High-Risk Percutaneous Coronary Intervention in Complex Coronary Disease.

Background: Mechanical circulatory support may facilitate high-risk percutaneous coronary intervention (PCI). This study aimed to assess the feasibility, safety and effectiveness of high-risk PCI under the support of venoarterial extracorporeal membrane oxygenation (VA-ECMO) combined with intra-aortic balloon pump (IABP). Methods: We enrolled patients who received VA-ECMO plus IABP-assisted PCI procedures at our center from April 2012 to June 2018. Major adverse cardiac events (MACEs) included all-cause death, myocardial infarction, and target vessel revascularization. Results: A total of 10 patients were included, with a mean age of 71 years, EuroSCORE II of 19.9%, and SYNTAX score of 39.8. Procedural success was achieved in nine (90%) patients. The mean duration of ECMO support was 1.5 hours, and 2.6 stents were implanted per patient. Major complications included contrast-induced nephropathy needing hemodialysis in one (10%) patient, significant hemoglobin drop requiring blood transfusion in two (20%) patients, pulmonary infection in one (10%) patient, and local surgical incision infection in one (10%) patient. The accumulative mortality rates for the nine patients with procedural success were 0, 22.2%, and 44.4% at 1, 3, and 5 years follow-up, respectively. However, cardiac death occurred in only one (11.1%) patient. In addition, two patients received repeat PCI or coronary artery bypass grafting within two years following the index procedure. The overall incidence rates of MACEs were 11.1%, 44.4%, and 66.7% at 1, 3, and 5 years follow-up, respectively. Conclusions: VA-ECMO plus IABP-assisted high-risk PCI was feasible in patients with complex coronary disease, with a high procedural success rate and acceptable mid-term clinical outcomes.

Fullerene on non-iron cluster-matrix co-catalysts promotes collaborative H2 and N2 activation for ammonia synthesis.

Developing highly effective catalysts for ammonia (NH3) synthesis is a challenging task. Even the current, prevalent iron-derived catalysts used for industrial NH3 synthesis require harsh reaction conditions and involve massive energy consumption. Here we show that anchoring buckminsterfullerene (C60) onto non-iron transition metals yields cluster-matrix co-catalysts that are highly efficient for NH3 synthesis. Such co-catalysts feature separate catalytic active sites for hydrogen and nitrogen. The 'electron buffer' behaviour of C60 balances the electron density at catalytic transition metal sites and enables the synergistic activation of nitrogen on transition metals in addition to the activation and migration of hydrogen on C60 sites. As demonstrated in long-term, continuous runs, the C60-promoting transition metal co-catalysts exhibit higher NH3 synthesis rates than catalysts without C60. With the involvement of C60, the rate-determining step in the cluster-matrix co-catalysis is found to be the hydrogenation of *NH2. C60 incorporation exemplifies a practical approach for solving hydrogen poisoning on a wide variety of oxide-supported Ru catalysts.

A system for efficient and sustainable cogeneration of water and electricity: Temperature difference induced by photothermal conversion and evaporative cooling.

Solar energy, with its sustainable properties, has garnered considerable attention for its potential to produce green electricity and clean water. This paper proposes a multistage energy transfer co-generation system (MWCNTs-covered thermoelectric module with aerogel and cooler, AC-CTEM) combining power generation and evaporative cooling. On the light-absorbing surface, the hot side of a thermoelectric module is covered with a hydrophobic coating made of PDMS and MWCNT. The cold side transfers heat to the evaporation zone using a heat sink. Aerogel evaporators are cross-linked with chitosan and polyurethane, which reduces the enthalpy of evaporation and facilitates efficient interfacial evaporation to remove heat and return it to refrigeration. Additionally, with the addition of Fresnel lenses and wind energy to the enhancement device, the system achieved an evaporation rate of 3.445 kg m-2 h-1 and an open-circuit voltage of 201.12 mV under 1 kW m-2 solar irradiation. The AC-CTEM system also demonstrated long-term stability and effectiveness in treating various types of non-potable water. Furthermore, we demonstrated the practical utility of the system by successfully cultivating grass seeds and powering electronic equipment. The AC-CTEM system exemplifies a practical energy-saving approach for the development of highly efficient co-generation systems.

Enhanced visible light responsive piezoelectric photocatalysis based on Bi2S3 coated BaTiO3 nanorods heterostructures.

Although the presence of the built-in electric field will solve the problem of carrier complexation in photocatalytic systems to some extent. However, free carriers will quickly shield the stabilized electric field and lose its effect. Therefore, how to introduce the dynamic piezoelectric field into the photocatalytic system has become an imminent problem. Herein, we developed an overcoated, visible light responsive, piezoelectric-assisted photocatalytic system by depositing Bi2S3 photocatalysts with a narrow-band system onto the surface of highly piezo-responsive BaTiO3 nanorods (BTO NRs). The heterojunction structure, bound by Bi-O chemical bonding, enhances carrier transport efficiency under the influence of the piezoelectric field. In the degradation experiments, the first-order rate constant for the degradation of chlortetracycline hydrochloride (CTC) in the BTO NRs/Bi2S3 system with the optimal complex ratio was 0.0276 min-1, which was 3.1 and 7.8 times higher than that of BTO NRs and Bi2S3, respectively. Additionally, we deduced the degradation pathways of CTC through a combination of Density functional theory (DFT) calculations and Liquid Chromatograph Mass Spectrometer (LC-MS), evaluating the toxicity of the intermediates. This complex system, featuring a highly photo-responsive semiconductor as a photo-acceptor deposited on a piezoelectric semiconductor surface providing a dynamic built-in electric field, enhances carrier separation efficiency under optimal light energy utilization conditions. These findings present novel and effective strategies for addressing two primary challenges in photocatalytic systems: low spectral utilization and significant photogenerated carrier complexation.

Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma.

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Topology-preserving segmentation of abdominal muscle layers from ultrasound images.

BACKGROUND: In clinical anesthesia, precise segmentation of muscle layers from abdominal ultrasound images is crucial for identifying nerve block locations accurately. Despite deep learning advancements, challenges persist in segmenting muscle layers with accurate topology due to pseudo and weak edges caused by acoustic artifacts in ultrasound imagery. PURPOSE: To assist anesthesiologists in locating nerve block areas, we have developed a novel deep learning algorithm that can accurately segment muscle layers in abdominal ultrasound images with interference. METHODS: We propose a comprehensive approach emphasizing the preservation of the segmentation's low-rank property to ensure correct topology. Our methodology integrates a Semantic Feature Extraction (SFE) module for redundant encoding, a Low-rank Reconstruction (LR) module to compress this encoding, and an Edge Reconstruction (ER) module to refine segmentation boundaries. Our evaluation involved rigorous testing on clinical datasets, comparing our algorithm against seven established deep learning-based segmentation methods using metrics such as Mean Intersection-over-Union (MIoU) and Hausdorff distance (HD). Statistical rigor was ensured through effect size quantification with Cliff's Delta, Multivariate Analysis of Variance (MANOVA) for multivariate analysis, and application of the Holm-Bonferroni method for multiple comparisons correction. RESULTS: We demonstrate that our method outperforms other industry-recognized deep learning approaches on both MIoU and HD metrics, achieving the best outcomes with 88.21%/4.98 ( p m a x = 0.1893 $p_{max}=0.1893$ ) on the standard test set and 85.48%/6.98 ( p m a x = 0.0448 $p_{max}=0.0448$ ) on the challenging test set. The best&worst results for the other models on the standard test set were (87.20%/5.72)&(83.69%/8.12), and on the challenging test set were (81.25%/10.00)&(71.74%/16.82). Ablation studies further validate the distinct contributions of the proposed modules, which synergistically achieve a balance between maintaining topological integrity and edge precision. CONCLUSIONS: Our findings validate the effective segmentation of muscle layers with accurate topology in complex ultrasound images, leveraging low-rank constraints. The proposed method not only advances the field of medical imaging segmentation but also offers practical benefits for clinical anesthesia by improving the reliability of nerve block localization.

Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71.

Human Enterovirus 71 (EV71) has emerged as one of the predominant causative agents of hand, foot and mouth disease (HFMD) with global impact. Despite the inactivated vaccine being licensed, other vaccine candidates based on advanced technology platforms are under development. In this report, we rationally designed and constructed two DNA-launched live attenuated vaccine candidates (pDL-EV71) under the control of specific promoters. In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71. More importantly, the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/ßR-/- mice, demonstrating its safety profile. Moreover, a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice. A single-dose immunization with 10 µg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice. Overall, our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.

Targeting renal damage: The ACE2/Ang-(1-7)/mas axis in chronic kidney disease.

The renin-angiotensin system (RAS) is a crucial factor in chronic kidney disease (CKD) progression, affecting renal function and contributing significantly to renal tissue inflammation and fibrosis. Activation of the classical ACE/Ang II/AT1 axis exacerbates renal damage, while the ACE2/Ang-(1-7)/Mas axis has shown promise in reducing CKD progression in numerous animal models. Recently, the ACE2/Ang-(1-7)/Mas axis has emerged as a promising target for CKD interventions. This review provides a comprehensive review of the pivotal role of this axis in CKD pathogenesis and systematically examines various molecules and pharmaceutical agents targeting this pathway. This review aims to elucidate potential strategies for delaying or halting CKD progression, offering patients more effective treatment options.