Background Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC. Materials and methods A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and R0 resection rate. Results The incidence of TRAEs from grades 1 to 4 was 43.5%, 34.8%, 13.0%, and 8.7%, respectively. Grade 3/4 TRAEs included neutropenia, fatigue, hyperglycemia, nausea and vomiting, decreased appetite, rash, and diarrhea. No treatment-related surgical delay was observed. The radiographic response rates were 5.0% (CR), 40.0% (PR), and 55.0% (SD). The ORR reached 45.0%. Eighteen patients underwent successful surgical resection. The R0 resection rate was 100%. The pathological response rates were 16.7% (pCR), 27.8% (MPR, two of five near-pCR), 16.7% (PPR), and 38.8% (NPR). CD4, CD8, CD20, and CD38 expression in the tumors significantly increased after neoadjuvant chemotherapy. The increase in CD20 levels after neoadjuvant treatment in patients with pCR/MPR was significantly higher than in patients with PPR/NPR. Conclusion Triweekly neoadjuvant toripalimab-GP is feasible and achieves promising pCR and MPR rates in patients with resectable locally advanced HNSCC. Trial registration Chinese clinical trial registry, ChiCTR2100043743, Registered 27 Febrary 2021- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120570

Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), poses a serious threat to human health. It is urgently needed to develop recognition tools and discover molecular targets for early diagnosis and targeted therapy of esophageal cancer. Here, we developed several DNA aptamers that can bind to ESCC KYSE410 cells with a nanomolar range of dissociation constants by using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). The selected A2 aptamer is found to strongly bind with multiple cancer cells, including several ESCC cell lines. Tissue imaging displayed that the A2 aptamer can specifically recognize clinical ESCC tissues but not the adjacent tissues. Moreover, we identified integrin β1 as the binding target of A2 through pulldown and RNA interference assays. Meanwhile, molecular docking and mutation assays suggested that A2 probably binds to integrin β1 through the nucleotides of DA16-DG21, and competitive binding and structural alignment assays indicated that A2 shares the overlapped binding sites with laminin and arginine−glycine−aspartate ligands. Furthermore, we engineered A2-induced targeted therapy for ESCC. By constructing A2-tethered DNA nanoassemblies carrying multiple doxorubicin (Dox) molecules as antitumor agents, inhibition of tumor cell growth in vitro and in vivo was achieved. This work provides a useful targeting tool and a potential molecular target for cancer diagnosis and targeted therapy and is helpful for understanding the integrin mechanism and developing integrin inhibitors.

In order to investigate the influence of the unit junction on the micromixer performance, a repetitive structure micromixer with a total length of 12.3 mm was proposed. This micromixer consists of a T-shape inlet channel and six cubic mixing units, as well as junctions between them. Numerical simulations show that, when the junctions are all located at the geometric center of the cubic mixing unit, the outlet mixing index is 72.12%. At the same flow velocity, the best mixing index achieved 97.15% and was increased by 34.68% when the junctions were located at different corners of the cubic mixing unit. The improvement in the mixing index illustrated that the non-equilibrium vortexes generated by changing the junction location to utilize the restricted diffusion by the mixing unit’s side wall could promote mixing. Visual tests of the micromixer chip prepared by 3D printing were consistent with the simulation results, also indicating that the junction location had a significant influence on the mixer’s performance. This article provides a new idea for optimizing the structural design and improving the performance of micromixers.

The splitter is an important component of water-based cooling systems used to extract heat from computer boards. In the present study, the flow characteristics of a 16-splitter structure were numerically simulated and compared with experimental results to verify the reliability of the numerical simulation method. Accordingly, the concept of splitter structural coefficients was proposed. Based on the results of this study, we recommend a selection range of 5 ≤ k ≤ 6 for the structure factor k of the splitter; after optimization, the maximum deviation of the splitter outlet flow was reduced from the original value of 100% to 8.3%.

When the free end of a microcantilever is modified by a genetic probe, this sensor can be used for a wider range of applications, such as for chemical analysis, biological testing, pharmaceutical screening, and environmental monitoring. In this paper, to clarify the preparation and detection process of a microcantilever sensor with genetic probe modification, the core procedures, such as probe immobilization, complementary hybridization, and signal extraction and processing, are combined and compared. Then, to reveal the microcantilever’s detection mechanism and analysis, the influencing factors of testing results, the theoretical research, including the deflection principle, the establishment and verification of a detection model, as well as environmental influencing factors are summarized. Next, to demonstrate the application results of the genetic-probe-modified sensors, based on the classification of detection targets, the application status of other substances except nucleic acid, virus, bacteria and cells is not introduced. Finally, by enumerating the application results of a genetic-probe-modified microcantilever combined with a microfluidic chip, the future development direction of this technology is surveyed. It is hoped that this review will contribute to the future design of a genetic-probe-modified microcantilever, with further exploration of the sensitive mechanism, optimization of the design and processing methods, expansion of the application fields, and promotion of practical application.