Surgical Resection for Small Cell Lung Cancer: Pneumonectomy versus Lobectomy

Background. There are some patients with SCLC that are diagnosed in the operating room by cryosection and surgeons had to perform surgical resection for these patients. The aim of this study is to compare the effective of pneumonectomy with lobectomy for SCLC. Methods. A retrospective study was undertaken in 75 patients with SCLC that were diagnosed by cryosection during surgery. 31 of them underwent pneumonectomy, 44 underwent lobectomy. Local recurrence rate and survival rate according to surgical procedures and cancer stages were analyzed. Results. There was significant difference in the overall survival rate between lobectomy and pneumonectomy groups (P = 0.044). For patients with stage II SCLC, the overall survival rate after pneumonectomy was significantly better than after lobectomy (P = 0.028). No significant difference in overall survival rate was found between the two surgical groups in patients with stage III SCLC (P = 0.933). The local recurrence rate in lobectomy group was significant higher that in pneumonectomy group (P = 0.0017). Conclusions. SCLC was responsive to surgical therapy. When surgeons have to select an appropriate method of operation for patients with SCLC during surgery, pneumonectomy may be the right choice for these patients. Pneumonectomy can result in significantly better local control and higher survival rate compare with lobectomy

Structural Insights into TIR Domain Specificity of the Bridging Adaptor Mal in TLR4 Signaling

MyD88 adaptor-like protein (Mal) is a crucial adaptor that acts as a bridge to recruit the MyD88 molecule to activated TLR4 receptors in response to invading pathogens. The specific assembly of the Toll/interleukin-1 receptor (TIR) domains of TLR4, Mal and MyD88 is responsible for proper signal transduction in the TLR4 signaling pathway. However, the molecular mechanism for the specificity of these TIR domains remains unclear. Here, we present the crystal structure of the TIR domain of the human Mal molecule (Mal-TIR) at a resolution of 2.4 Å. Unexpectedly, Mal-TIR exhibits an extraordinarily long AB loop, but no αB helix or BB loop, distinguishing it from other TIR domains. More importantly, the Mal-TIR AB loop is capable of mediating direct binding to the TIR domains of TLR4 and MyD88 simultaneously. We also found that Mal-TIR can form a back-to-back dimer that may resemble the dimeric assembly of the entire Mal molecule. Our data demonstrate the bridge role of the Mal-TIR domain and provide important information about TIR domain specificity

A novel technique for lymphadenectomy along the left recurrent laryngeal nerve during minimally invasive esophagectomy: a retrospective cohort study

Abstract Background In the context of esophageal cancers, lymph nodes located along the left recurrent laryngeal nerve (RLN) exhibit significant involvement, posing significant challenges for lymphadenectomy. The objective of this study is to assess the safety and efficacy of a novel technique for lymphadenectomy called "elastic suspension of left RLN" method, comparing it with the conventional approach. Methods Between January 2016 and June 2020, a total of 393 patients who underwent minimally invasive esophagectomy with gastroplasty and cervical esophagogastric anastomosis were enrolled in the study. Among them, 291 patients underwent the "elastic suspension of left RLN" method, while 102 patients underwent the conventional method. We compared the number of harvested lymph nodes along the left RLN and assessed postoperative complications between these two groups. Additionally, the overall survival (OS) rate was calculated and analyzed for the entire cohort. Results In comparison to the conventional group, the elastic suspension group exhibited a higher yield of harvested lymph nodes along the left RLN (5.36 vs 3.07, P < 0.001). Moreover, the incidence of postoperative hoarseness was lower in the elastic suspension group (10.65% vs 18.63%, P = 0.038). The average duration of lymphadenectomy along the left RLN was 11.85 min in the elastic suspension group and 11.51 min in the conventional group, although this difference was not statistically significant (P = 0.091). Notably, the overall 5-year OS was markedly higher in the elastic suspension group compared to the conventional group (64.1% vs. 50.1%, P = 0.020). Conclusions The findings suggest that the novel "elastic suspension of left RLN" method for lymphadenectomy along the left RLN in minimally invasive esophagectomy is both safe and effective. This technique holds promise for widespread adoption in esophagectomy procedures

Uncooled Broadband Photodetection <i>via</i> Light Trapping in Conformal PtTe₂–Silicon Nanopillar Heterostructures

Dirac semimetals have demonstrated significant attraction in the field of optoelectronics due to their unique bandgap structure and high carrier mobility. Combining them with classical semiconductor materials to form heterojunctions enables broadband optoelectronic conversion at room temperature. However, the low light absorption of layered Dirac semimetals substantially limits the device’s responsivity in the infrared band. Herein, a three-dimensional (3D) heterostructure, composed of silicon nanopillars (SiNPs) and a conformal PtTe2 film, is proposed and demonstrated to enhance the photoresponsivity for uncooled broadband detection. The light trapping effect in the 3D heterostructure efficiently promotes the interaction between light and PtTe2, while also enhancing the light absorption efficiency of silicon, which enables the enhancement of the device responsivity across a broadband spectrum. Experimentally, the PtTe2-SiNPs heterojunction device demonstrates excellent photoelectric conversion behavior across the visible, near-infrared, and long-wave infrared (LWIR) bands, with its responsivity demonstrating an order-of-magnitude improvement compared to the counterparts with planar silicon heterojunctions. Under 11 μm laser irradiation, the noise equivalent power (NEP) can reach 1.76 nW·Hz–1/2 (@1 kHz). These findings offer a strategic approach to the design and fabrication of high-performance broadband photodetectors based on Dirac semimetals

Targeting VCP potentiates immune checkpoint therapy for colorectal cancer

Summary: Immune checkpoint blockade therapies are still ineffective for most patients with colorectal cancer (CRC). Immunogenic cell death (ICD) enables the release of key immunostimulatory signals to drive efficient anti-tumor immunity, which could be used to potentiate the effects of immune checkpoint inhibitors. Here, we showed that inhibition of valosin-containing protein (VCP) elicits ICD in CRC. Meanwhile, VCP inhibitor upregulates PD-L1 expression and compromises anti-tumor immunity in vivo. Mechanistically, VCP transcriptionally regulates PD-L1 expression in a JAK1-dependent manner. Combining VCP inhibitor with anti-PD1 remodels tumor immune microenvironment and reduces tumor growth in mouse models of CRC. Addition of oncolytic virus further augments the therapeutic activity of the combination regimen. Our study shows the molecular mechanism for regulating PD-L1 expression by VCP and suggests that inhibition of VCP has the potential to increase the efficacy of immunotherapy in CRC

Epigenetic regulation of CD271, a potential cancer stem cell marker associated with chemoresistance and metastatic capacity

Cancer stem cells (CSCs) are considered to be the cause of tumor initiation, metastasis and recurrence. Additionally, CSCs are responsible for the failure of chemotherapy and radiotherapy. The isolation and identification of CSCs is crucial for facilitating the monitoring, therapy or prevention of cancer. We aimed to identify esophageal squamous cell carcinoma (ESCC) stem-like cells, the epigenetic mechanism and identify novel biomarkers for targeting ESCC CSCs. Sixty-three paired ESCC tissues and adjacent non-cancerous tissues were included in this study. CD271, which was identified as the CSC marker for melanoma, was assessed using quantitative PCR (qPCR). Using flow cytometry, we isolated CD271(+) cells comprising 7.5% of cancer cells from the KYSE70 cell line. Sphere formation and anchorage-independent growth were analyzed in CD271(+) and CD271(−) cancer cells, respectively. qPCR was used to detect stem-related genes and CCK-8 was performed to analyze the sensitivity to chemotherapy in the two groups. Bisulfite genomic sequencing was used to analyze the methylation status. CD271 expression was significantly higher in ESCC tissues than in adjacent non-cancerous tissues. Compared with CD271(−) cancer cells, CD271(+) cancer cells showed a higher ability of sphere and colony formation, a high level expression of stem-related gene, and resistance to chemotherapy. The expression of CD271 was induced by a demethylation agent. In conclusion, CD271(+) ESCC cells possess stem-like properties. CD271 can potentially act as a prognostic marker for ESCC, whose expression is regulated epigenetically