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Abstract Background The purpose of this retrospective study was to compare the safety and feasibility of single-intercostal totally minimally invasive Ivor Lewis esophagectomy (MIIE) with those of multiple-intercostal MIIE. Methods Between January 2016 and December 2022, clinical data were collected for 528 patients who successfully underwent totally minimally invasive esophagectomy. Among these patients, 294 underwent MIIE, with 200 undergoing the single-intercostal approach and 94 undergoing the multiple-intercostal approach. Propensity score matching (PSM) was applied to the cohort of 294 patients. Subsequently, perioperative outcomes and other pertinent clinical data were analyzed retrospectively. Results A total of 294 patients were subjected to PSM, and 89 groups of patient data (178 persons in total) were well balanced and included in the follow-up statistics. Compared to the multiple intercostal group, the single intercostal group had a shorter operative time (280 min vs. 310 min; p 0.05). The total number of lymph nodes sampled (25.30 vs. 27.55, p > 0.05) and recurrent laryngeal nerve lymph nodes sampled on the both sides (p > 0.05) did not significantly differ. The single intercostal group had lower postoperative long-term usage of morphine (0,0–60 vs. 20,20–130; p 0.05). Conclusions Both techniques can be used for the treatment of esophageal cancer. Compared to multiple intercostal MIIE, the feasibility of which has been proven internationally, the single intercostal technique can also be applied to patients of different age groups and sexes and with different tumor locations. It can provide surgeons with an additional surgical option. Trial registration This study was retrospectively registered by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine, and written informed consent was exempted from ethical review. The registration number was 20,230,326. The date of registration was 2023.03.26.

Background Esophageal cancer (ESCA) is a form of malignant tumor associated with chronic inflammation and immune dysregulation. However, the specific immune status and key mechanisms of immune regulation in this disease require further exploration.Methods To investigate the features of the human ESCA tumor immune microenvironment and its possible regulation, we performed mass cytometry by time of flight, single-cell RNA sequencing, multicolor fluorescence staining of tissue, and flow cytometry analyses on tumor and paracancerous tissue from treatment-naïve patients.Results We depicted the immune landscape of the ESCA and revealed that CD8+ (tissue-resident memory CD8+ T cells (CD8+ TRMs) were closely related to disease progression. We also revealed the heterogeneity of CD8+ TRMs in the ESCA tumor microenvironment (TME), which was associated with their differentiation and function. Moreover, the subset of CD8+ TRMs in tumor (called tTRMs) that expressed high levels of granzyme B and immune checkpoints was markedly decreased in the TME of advanced ESCA. We showed that tTRMs are tumor effector cells preactivated in the TME. We then demonstrated that conventional dendritic cells (cDC2s) derived from intermediate monocytes (iMos) are essential for maintaining the proliferation of CD8+ TRMs in the TME. Our preliminary study showed that hypoxia can promote the apoptosis of iMos and impede the maturation of cDC2s, which in turn reduces the proliferative capacity of CD8+ TRMs, thereby contributing to the progression of cancer.Conclusions Our study revealed the essential antitumor roles of CD8+ TRMs and preliminarily explored the regulation of the iMo/cDC2/CD8+ TRM immune axis in the human ESCA TME.

Summary: Background: In resectable oesophageal squamous cell carcinoma (ESCC), the efficacy of camrelizumab combined with chemotherapy and apatinib followed by minimally invasive oesophagectomy is not clear. We aimed to fill this knowledge gap. Methods: This investigator-initiated, single-arm, prospective, phase 2 trial was performed at the Second Affiliated Hospital of Zhejiang University, China. Patients (aged 18–75 years) who were histologically or cytologically diagnosed with ESCC were deemed suitable to participate in this trial. Patients received 2–3 cycles of neoadjuvant therapy with camrelizumab, nedaplatin, albumin paclitaxel, and apatinib; each cycle was repeated every 14 days. Surgery occurred 4–6 weeks after the last neoadjuvant treatment cycle. The primary outcome was the pathological complete response (PCR) rate of the tumour and lymph nodes. The changes in the peripheral blood immunoprofile among patients without PCR (ie, non-PCR [NPCR]) and with PCR were assessed by mass cytometry. This study was registered with ClinicalTrials.gov, NCT04666090. Findings: 42 patients were enrolled between November 23, 2020 and December 31, 2022. The disease control rate was 100.0% (95% CI, 91.6–100%), and the objective response rate was 83.3% (95% CI, 68.6–93.0%). Six (14.3%) patients experienced grade 3 adverse events. The most common were white blood cell count decrease (31.0%), alopecia (81.0%), asthenia (38.1%), and reactive cutaneous capillary endothelial proliferation (35.7%). 41 patients received minimally invasive oesophagectomy; all 41patients achieved R0 resection, and 18 (43.9%, 95% CI, 28.5–60.3%) patients achieved PCR. The median follow-up was 23 months and the 2-year survival rate was 85.9%. T-cell subsets in both the PCR and NPCR groups exhibited consistency in response to neoadjuvant therapy. In contrast, some of natural killer (NK) cells (NK-C03, NK-C11), B cells (B-C06) and monocytes (M-C05), exhibited significant differences between the PCR and NPCR groups before neoadjuvant therapy. M-C06 had a significant difference in the PCR group and NPCR group after neoadjuvant therapy. NK-C12 and B-C15 showed significant differences both before and after neoadjuvant therapy. Interpretation: The application of camrelizumab, chemotherapy and apatinib in the neoadjuvant setting for locally advanced ESCC has shown promising antitumour activity and an acceptable safety profile in this single-arm study. In the neoadjuvant setting, NK cell, B cell, and monocyte subsets exhibited greater predictive power for immunotherapy responsiveness than T-cell subsets. Longer follow-up to assess survival outcomes and a phase 3 randomised trial are needed to further evaluate the proposed treatment. Funding: The China Anti-Cancer Association and the “Leading Goose” Research and Development Project of Zhejiang Province.

Abstract Revealing the electrocatalytic microstructure is the basis for finding more efficient and stable electrode materials for clean energy conversion devices. However, there is still a lack of direct understanding of the phase transition process of the sample during heating, which makes the synthesis conditions of the catalyst often rely on experienced guidance. Herein, ZIF‐8@α‐Co(OH)2 core‐shell structure and uniformly coated α‐Co(OH)2 nanosheets on the surface of ZIF‐8 are synthesized. The effect of temperature on microstructure evolution is studied by in situ heating technique with high‐resolution transmission electron microscopy. Based on understanding the relationship between temperature, microstructure, and OER properties, a simple annealing synthesis strategy is designed effectively. During the annealing process, ZnO@CoO heterogeneous structure is formed at 400 °C, and the material reached a stable hydroxyl oxide structure after electrochemical cycle voltammetry in an alkaline solution. The OER performance test shows that the commercial IrO2 catalyst has comparable catalytic performance.

Histopathology is a critical approach for diagnostic tasks and precision treatment. However, histopathological deep learning tools for auto‐identification remain poorly developed. Meanwhile, the interpretation of the computer vision attention into a cellular process is less efficient in a systematic way. Herein, it is identified that histone acetyltransferase 1 (HAT1) is an aging‐associated gene in the esophagus epithelium by machine learning. An interpretable deep learning model is developed to distinguish morphological changes with varied HAT1 expressions in esophageal squamous carcinoma cells (ESCC). The gradient‐weighted class activation mapping and prediction score analysis reveal that the computer's vision focuses on the nuclear sizes of ESCC. The hypothesized phenotype is verified in HAT1‐knockdown ESCCs. Finally, HAT1 regulating cell senescence by affecting the H3K27 acetylation and E2F transcription factor 7 (E2F7) expression is shown. Herein, the feasibility and benefits of applying histopathological deep learning assistance systems in routine practice scenarios and connecting phenotype and genotype for further genetic research are suggested.

BackgroundLung cancer is the leading cause of mortality in cancer patients. N7-methylguanosine (m7G) modification as a translational regulation pattern has been reported to participate in multiple types of cancer progression, but little is known in lung cancer. This study attempts to explore the role of m7G-related proteins in genetic and epigenetic variations in lung adenocarcinoma, and its relationship with clinical prognosis, immune infiltration, and immunotherapy.MethodsSequencing data were obtained from the Genomic Data Commons (GDC) Data Portal and Gene Expression Omnibus (GEO) databases. Consensus clustering was utilized to distinguish m7G clusters, and responses to immunotherapy were also evaluated. Moreover, univariate and multivariate Cox and Least absolute shrinkage and selection operator LASSO Cox regression analyses were used to screen independent prognostic factors and generated risk scores for constructing a survival prediction model. Multiple cell types such as epithelial cells and immune cells were identified to verify the bulk RNA results. Short hairpin RNA (shRNA) Tet-on plasmids, Clustered Regularly Interspaced Short Palindromic Repeats CRISPR/Cas9 for knockout plasmids, and nucleoside diphosphate linked to moiety X-type motif 4 (NUDT4) overexpression plasmids were constructed to inhibit or promote tumor cell NUDT4 expression, then RT-qPCR, Cell Counting Kit-8 CCK8 proliferation assay, and Transwell assay were used to observe tumor cell biological functions.ResultsFifteen m7G-related genes were highly expressed in tumor samples, and 12 genes were associated with poor prognosis. m7G cluster-B had lower immune infiltration level, worse survival, and samples that predicted poor responses to immunotherapy. The multivariate Cox model showed that NUDT4 and WDR4 (WD repeat domain 4) were independent risk factors. Single-cell m7G gene set variation analysis (GSVA) scores also had a negative correlation tendency with immune infiltration level and T-cell Programmed Death-1 PD-1 expression, but the statistics were not significant. Knocking down and knocking out the NUDT4 expression significantly inhibited cell proliferation capability in A549 and H1299 cells. In contrast, overexpressing NUDT4 promoted tumor cell proliferation. However, there was no difference in migration capability in the knockdown, knockout, or overexpression groups.ConclusionsOur study revealed that m7G modification-related proteins are closely related to the tumor microenvironment, immune cell infiltration, responses to immunotherapy, and patients’ prognosis in lung adenocarcinoma and could be useful biomarkers for the identification of patients who could benefit from immunotherapy. The m7G modification protein NUDT4 may be a novel biomarker in promoting the progression of lung cancer.

Abstract Room‐temperature sodium–sulfur (RT Na–S) batteries are arousing great interest in recent years. Their practical applications, however, are hindered by several intrinsic problems, such as the sluggish kinetic, shuttle effect, and the incomplete conversion of sodium polysulfides (NaPSs). Here a sulfur host material that is based on tungsten nanoparticles embedded in nitrogen‐doped graphene is reported. The incorporation of tungsten nanoparticles significantly accelerates the polysulfides conversion (especially the reduction of Na2S4 to Na2S, which contributes to 75% of the full capacity) and completely suppresses the shuttle effect, en route to a fully reversible reaction of NaPSs. With a host weight ratio of only 9.1% (about 3–6 times lower than that in recent reports), the cathode shows unprecedented electrochemical performances even at high sulfur mass loadings. The experimental findings, which are corroborated by the first‐principles calculations, highlight the so far unexplored role of tungsten nanoparticles in sulfur hosts, thus pointing to a viable route toward stable Na–S batteries at room temperatures.

Lung ischemia-reperfusion injury (LIRI) is associated with many diseases, including primary graft dysfunction after lung transplantation, and has no specific and effective therapies. Necroptosis contributes to the pathogenesis of ischemia-reperfusion injury. Necrostatin-1 (Nec-1), the necroptosis inhibitor targeting RIPK1, has been reported to alleviate ischemia-reperfusion injury in various organs. However, the underlying mechanism of Nec-1 in LIRI remains unclear. In this paper, an in vivo LIRI model was built up by left lung hilar clamping in mice, and an in vitro cold ischemia-reperfusion (CI/R) model using BEAS-2B cells was applied to mimic the lung transplantation setting. We found Nec-1 significantly alleviated ischemia-reperfusion-induced lung injury, cytokine releasing, and necroptosis of epithelial cells in mouse lungs. In vitro, Nec-1 also mitigated CI/R-induced cell death and inflammatory responses in BEAS-2B cells, and these protective effects were achieved by simultaneously inhibiting the formation of necrosome and RIPK1-dependent apoptosis. However, Nec-1 decreased the necrosome number but increased the apoptosis level in lung tissues after ischemia reperfusion. We further clarified that Nec-1 could also attenuate lung injury by promoting neutrophil apoptosis from flow cytometry. In conclusion, Nec-1 alleviated lung ischemia-reperfusion injury by inhibiting necroptosis and apoptosis of epithelial cells and promoting the apoptosis of neutrophils. Thus, Nec-1 could be a promising medication against primary graft dysfunction after lung transplantation.